Cancer Research and Treatment

Original Articles

Gynecologic cancer

Impact of the Learning Curve on the Survival of Abdominal or Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer: Lan Ying Li, Lan Ying Wen, Sun Hee Park, Eun Ji Nam, Jung Yun Lee, Sunghoon Kim, Young Tae Kim, Sang Wun Kim; Cancer Res Treat. 2021;53(1):243-251. Published online October 12, 2020; DOI: https://doi.org/10.4143/crt.2020.063

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Purpose
The objective of this study was to define the learning curve required to attain satisfactory oncologic outcomes of cervical cancer patients who were undergoing open or minimally invasive surgery for radical hysterectomy, and to analyze the correlation between the learning curve and tumor size.
Materials and Methods
Cervical cancer patients (stage IA-IIA) who underwent open radical hysterectomy (n=280) or minimal invasive radical hysterectomy (n=282) were retrospectively reviewed. The learning curve was evaluated using cumulative sum of 5-year recurrence rates. Survival outcomes were analyzed based on the operation period (“learning period,” P1 vs. “skilled period,” P2), operation mode, and tumor size.
Results
The 5-year disease-free and overall survival rates between open and minimally invasive groups were 91.8% and 89.0% (p=0.098) and 96.1% and 97.2% (p=0.944), respectively. The number of surgeries for learning period was 30 and 60 in open and minimally invasive group, respectively. P2 had better 5-year disease-free survival than P1 after adjusting for risk factors (hazard ratio, 0.392; 95% confidence interval, 0.210 to 0.734; p=0.003). All patients with tumors < 2 cm had similar 5-year disease-free survival regardless of operation mode or learning curve. Minimally invasive group presented lower survival rates than open group when tumors ≥ 2 cm in P2. Preoperative conization improved disease-free survival in patients with tumors ≥ 2 cm, especially in minimally invasive group.
Conclusion
Minimally invasive radical hysterectomy required more cases than open group to achieve acceptable 5-year disease-free survival. When tumors ≥ 2 cm, the surgeon’s proficiency affected survival outcomes in both groups.

Citations

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Radical Hysterectomy With Preoperative Conization in Early-Stage Cervical Cancer: A Systematic Review and Pairwise and Network Meta-Analysis
Xinbin Zhu, Lele Ye, Yunfeng Fu, Bingbing You, Weiguo Lu
Journal of Minimally Invasive Gynecology.2024; 31(3): 193. CrossRef
Minimally invasive radical hysterectomy and the importance of avoiding cancer cell spillage for early-stage cervical cancer: a narrative review
Atsushi Fusegi, Hiroyuki Kanao, Shiho Tsumura, Atsushi Murakami, Akiko Abe, Yoichi Aoki, Hidetaka Nomura
Journal of Gynecologic Oncology.2023;[Epub] CrossRef
Association of Hospital Surgical Volume With Survival in Early-Stage Cervical Cancer Treated With Radical Hysterectomy
Nicolò Bizzarri, Lukáš Dostálek, Luc R. C. W. van Lonkhuijzen, Diana Giannarelli, Aldo Lopez, Henrik Falconer, Denis Querleu, Ali Ayhan, Sarah H. Kim, David Isla Ortiz, Jaroslav Klat, Fabio Landoni, Juliana Rodriguez, Ranjit Manchanda, Jan Kosťun, Pedro T
Obstetrics & Gynecology.2023; 141(1): 207. CrossRef
Learning Laparoscopic Radical Hysterectomy: Are We Facing an Emerging Situation?
Graziella Moufawad, Antonio Simone Laganà, Nassir Habib, Vito Chiantera, Andrea Giannini, Federico Ferrari, Amerigo Vitagliano, Luigi Della Corte, Giuseppe Bifulco, Zaki Sleiman
International Journal of Environmental Research and Public Health.2023; 20(3): 2053. CrossRef
Breast Reconstruction with DIEP Flap: The Learning Curve at a Breast Reconstruction Center and a Single-Surgeon Study
Charalampos Varnava, Philipp Wiebringhaus, Tobias Hirsch, Alexander Dermietzel, Maximilian Kueckelhaus
Journal of Clinical Medicine.2023; 12(8): 2894. CrossRef
A meta-analysis of survival after minimally invasive radical hysterectomy versus abdominal radical hysterectomy in cervical cancer: center-associated factors matter
Si Sun, Jing Cai, Ruixie Li, Yujia Wang, Jing Zhao, Yuhui Huang, Linjuan Xu, Qiang Yang, Zehua Wang
Archives of Gynecology and Obstetrics.2022; 306(3): 623. CrossRef
Comparison of Minimally Invasive Versus Abdominal Radical Hysterectomy for Early-Stage Cervical Cancer: An Updated Meta-Analysis
Mengting Zhang, Wei Dai, Yuexiu Si, Yetan Shi, Xiangyuan Li, Ke Jiang, Jingyi Shen, Liying Ying
Frontiers in Oncology.2022;[Epub] CrossRef
Assessment of ESGO Quality Indicators in Cervical Cancer Surgery: A Real-World Study in a High-Volume Chinese Hospital
Yan Ding, Xuyin Zhang, Junjun Qiu, Jianfeng Zhang, Keqin Hua
Frontiers in Oncology.2022;[Epub] CrossRef
Trends in Surgical Morbidity and Survival Outcomes for Radical Hysterectomy in West China: An 11-Year Retrospective Cohort Study
Huining Jing, Ying Yang, Yinxia Liu, Peijun Zou, Zhengyu Li
Frontiers in Oncology.2022;[Epub] CrossRef
Comparison of Prognosis between Minimally Invasive and Abdominal Radical Hysterectomy for Patients with Early-Stage Cervical Cancer
Tomohito Tanaka, Shoko Ueda, Shunsuke Miyamoto, Sousuke Hashida, Shinichi Terada, Hiromi Konishi, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
Current Oncology.2022; 29(4): 2272. CrossRef
Open versus minimally invasive radical hysterectomy for early cervical cancer: A two-center retrospective cohort study with pathologic review of usual-type adenocarcinoma and adenosquamous carcinoma
Yeorae Kim, Se Ik Kim, Hyojin Kim, Maria Lee, Hee Seung Kim, Kidong Kim, Hyun Hoon Chung, Jae Hong No, Yong Beom Kim, Jae-Weon Kim, Noh Hyun Park, Yong-Sang Song, Cheol Lee, Dong Hoon Suh
Gynecologic Oncology.2022; 167(1): 28. CrossRef
Laparoscopic Versus Abdominal Radical Hysterectomy for Cervical Cancer
Fuyun Zhang, Xiaomei Song
American Journal of Clinical Oncology.2022; 45(11): 465. CrossRef
Surgical Approach and Use of Uterine Manipulator Are Not Associated with LVSI in Surgery for Early-stage Cervical Cancer
Yinxia Liu, Shuying Huang, Xiu Ming, Huining Jing, Zhengyu Li
Journal of Minimally Invasive Gynecology.2021; 28(9): 1573. CrossRef
Minimally Invasive Radical Hysterectomy for Cervical Cancer: A Systematic Review and Meta-analysis
Anna Jo Bodurtha Smith, Tiffany Nicole Jones, Diana Miao, Amanda Nickles Fader
Journal of Minimally Invasive Gynecology.2021; 28(3): 544. CrossRef
The Surgeon’s Proficiency Affected Survival Outcomes of Minimally Invasive Surgery for Early-Stage Cervical Cancer: A Retrospective Study of 851 Patients
Ying Yang, Yue Huang, Zhengyu Li
Frontiers in Oncology.2021;[Epub] CrossRef
MicroRNA-300 Inhibits the Proliferation and Metastasis of Cervical Cancer Cells via Posttranscriptional Suppression of G Protein-Coupled Receptor 34 (GPR34)
Mei Wang, Ying Tian, Lin Miao, Wenxia Zhao, Antonio Raffone
Journal of Oncology.2021; 2021: 1. CrossRef

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Early Assessment of Response to Neoadjuvant Chemotherapy with ¹⁸F-FDG-PET/CT in Patients with Advanced-Stage Ovarian Cancer: Young Shin Chung, Hyun-Soo Kim, Jung-Yun Lee, Won Jun Kang, Eun Ji Nam, Sunghoon Kim, Sang Wun Kim, Young Tae Kim; Cancer Res Treat. 2020;52(4):1211-1218. Published online April 28, 2020; DOI: https://doi.org/10.4143/crt.2019.506

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Purpose
The aim of this study was to evaluate the ability of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) after one cycle of neoadjuvant chemotherapy (NAC) to predict chemotherapy response before interval debulking surgery (IDS) in advanced-stage ovarian cancer patients.
Materials and Methods
Forty consecutive patients underwent ¹⁸F-FDG-PET/CT at baseline and after one cycle of NAC. Metabolic responses were assessed by quantitative decrease in the maximum standardized uptake value (SUV_max) with PET/CT. Decreases in SUV_max were compared with cancer antigen 125 (CA-125) level before IDS, response rate by Response Evaluation Criteria in Solid Tumors criteria before IDS, residual tumor at IDS, and I chemotherapy response score (CRS) at IDS.
Results
A 40% cut-off for the decrease in SUVmax provided the best performance to predict CRS 3 (compete or near-complete pathologic response), with sensitivity, specificity, and accuracy of 81.8%, 72.4%, and 72.4%, respectively. According to this 40% cut-off, there were 17 (42.5%) metabolic responders (≥ 40%) and 23 (57.5%) metabolic non-responders (< 40%). Metabolic responders had higher rate of CRS 3 (52.9% vs. 8.7%, p=0.003), CA-125 normalization (< 35 U/mL) before IDS (76.5% vs. 39.1%, p=0.019), and no residual tumor at IDS (70.6% vs. 31.8%, p=0.025) compared with metabolic non-responders. There were significant associations with progression-free survival (p=0.021) between metabolic responders and non-responders, but not overall survival (p=0.335).
Conclusion
Early assessment with ¹⁸F-FDG-PET/CT after one cycle of NAC can be useful to predic response to chemotherapy before IDS in patients with advanced-stage ovarian cancer.

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The Evaluation Value of CT in the Efficacy of Neoadjuvant Chemotherapy in Ovarian Cancer Patients
Daying Mou, Shengyan Xie, Pingyuan Li, Mohammad Farukh Hashmi
Contrast Media & Molecular Imaging.2022;[Epub] CrossRef
Radiomics Analysis of PET and CT Components of 18F-FDG PET/CT Imaging for Prediction of Progression-Free Survival in Advanced High-Grade Serous Ovarian Cancer
Xihai Wang, Zaiming Lu
Frontiers in Oncology.2021;[Epub] CrossRef

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Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer: Lan Ying Li, Hee Jung Kim, Sun Ae Park, So Hyun Lee, Lee Kyung Kim, Jung Yun Lee, Sunghoon Kim, Young Tae Kim, Sang Wun Kim, Eun Ji Nam; Cancer Res Treat. 2019;51(3):1117-1127. Published online November 6, 2018; DOI: https://doi.org/10.4143/crt.2018.405

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Purpose
Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing.
Materials and Methods
To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA).
Results
Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25, HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845).
Conclusion
We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.

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Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
Journal of Clinical Medicine.2024; 13(9): 2718. CrossRef
Uncovering miRNA–mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors
Łukasz Biegała, Damian Kołat, Arkadiusz Gajek, Elżbieta Płuciennik, Agnieszka Marczak, Agnieszka Śliwińska, Michał Mikula, Aneta Rogalska
Cells.2024; 13(10): 867. CrossRef
Patient-derived xenograft models in cancer therapy: technologies and applications
Yihan Liu, Wantao Wu, Changjing Cai, Hao Zhang, Hong Shen, Ying Han
Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef
Deregulations of RNA Pol II Subunits in Cancer
Martina Muste Sadurni, Marco Saponaro
Applied Biosciences.2023; 2(3): 459. CrossRef
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Jiage Dai, Jiabao Cai, Taipeng Zhang, Mingyue Pang, Xiaoling Xu, Jiahua Bai, Yan Liu, Yusheng Qin
Genes.2023; 14(10): 1848. CrossRef
Prediction of Chemoresistance—How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer
Jacek Wilczyński, Edyta Paradowska, Justyna Wilczyńska, Miłosz Wilczyński
Current Oncology.2023; 31(1): 229. CrossRef
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Jacek Wilczyński, Edyta Paradowska, Miłosz Wilczyński
Journal of Personalized Medicine.2023; 14(1): 49. CrossRef
PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors
Julia C. F. Quintanilha, Alessandro Racioppi, Jin Wang, Amy S. Etheridge, Stefanie Denning, Carol E. Peña, Andrew D. Skol, Daniel J. Crona, Danyu Lin, Federico Innocenti
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Eros Azzalini, Domenico Tierno, Michele Bartoletti, Renzo Barbazza, Giorgio Giorda, Fabio Puglisi, Sabrina Chiara Cecere, Nunzia Simona Losito, Daniela Russo, Giorgio Stanta, Vincenzo Canzonieri, Serena Bonin
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Yeon-Ju Huh, Sung-Yup Cho, Min-Sun Cho, Kyoung-Eun Lee, Joo-Ho Lee
Genes & Genomics.2022; 44(11): 1425. CrossRef
Validation of a Patient-Derived Xenograft Model for Cervical Cancer Based on Genomic and Phenotypic Characterization
Shunsuke Miyamoto, Tomohito Tanaka, Kensuke Hirosuna, Ruri Nishie, Shoko Ueda, Sousuke Hashida, Shinichi Terada, Hiromi Konishi, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
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Yan Liu, Xue-Bing Jing, Zhen-Cheng Wang, Qing-Kun Han
Human Genomics.2021;[Epub] CrossRef
Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer
Sandra Muñoz-Galván, Amancio Carnero
Cancers.2021; 13(16): 4029. CrossRef
CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate
Aalia Batool, Hao Liu, Yi-Xun Liu, Su-Ren Chen
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Marc J Gallenito, Tahir S Qasim, Jasmine N Tutol, Ved Prakash, Sheel C Dodani, Gabriele Meloni
Metallomics.2020; 12(10): 1542. CrossRef
Function, Regulation and Biological Roles of PI3Kγ Variants
Bernd Nürnberg, Sandra Beer-Hammer
Biomolecules.2019; 9(9): 427. CrossRef

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Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer according to Tumorigenicity in Patient-Derived Xenograft Models: Kyung Jin Eoh, Young Shin Chung, So Hyun Lee, Sun-Ae Park, Hee Jung Kim, Wookyeom Yang, In Ok Lee, Jung-Yun Lee, Hanbyoul Cho, Doo Byung Chay, Sunghoon Kim, Sang Wun Kim, Jae-Hoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2018;50(3):956-963. Published online October 17, 2017; DOI: https://doi.org/10.4143/crt.2017.181

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Purpose
Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients.
Materials and Methods
Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity.
Results
Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers.
Conclusions
Tumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.

Citations

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TOWARDS Study: Patient-Derived Xenograft Engraftment Predicts Poor Survival in Patients With Newly Diagnosed Triple-Negative Breast Cancer
Christos Vaklavas, Cindy B. Matsen, Zhengtao Chu, Kenneth M. Boucher, Sandra D. Scherer, Satya Pathi, Anna Beck, Kirstyn E. Brownson, Saundra S. Buys, Namita Chittoria, Elyse D'Astous, H. Evin Gulbahce, N. Lynn Henry, Stephen Kimani, Jane Porretta, Regina
JCO Precision Oncology.2024;[Epub] CrossRef
Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice
Mingtang Zeng, Zijing Ruan, Jiaxi Tang, Maozhu Liu, Chengji Hu, Ping Fan, Xinhua Dai
Cancer Cell International.2023;[Epub] CrossRef
Cancer “Avatars”: Patient-Derived Xenograft Growth Correlation with Postoperative Recurrence and Survival in Pancreaticobiliary Cancer
Isaac T Lynch, Amro M Abdelrahman, Roberto Alva-Ruiz, Alessandro Fogliati, Rondell P Graham, Rory Smoot, Mark J Truty
Journal of the American College of Surgeons.2023; 237(3): 483. CrossRef
Identification of Prognostic Markers of Gynecologic Cancers Utilizing Patient-Derived Xenograft Mouse Models
Ha-Yeon Shin, Eun-ju Lee, Wookyeom Yang, Hyo Sun Kim, Dawn Chung, Hanbyoul Cho, Jae-Hoon Kim
Cancers.2022; 14(3): 829. CrossRef
Experimental models for ovarian cancer research
Sum In Tsang, Ayon A. Hassan, Sally K.Y. To, Alice S.T. Wong
Experimental Cell Research.2022; 416(1): 113150. CrossRef
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Alessandra Ciucci, Marianna Buttarelli, Anna Fagotti, Giovanni Scambia, Daniela Gallo
Cellular and Molecular Life Sciences.2022;[Epub] CrossRef
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Tianyu Qin, Junpeng Fan, Funian Lu, Li Zhang, Chen Liu, Qiyue Xiong, Yang Zhao, Gang Chen, Chaoyang Sun
Journal of Experimental & Clinical Cancer Research.2022;[Epub] CrossRef
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Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review
Tomohito Tanaka, Ruri Nishie, Shoko Ueda, Shunsuke Miyamoto, Sousuke Hashida, Hiromi Konishi, Shinichi Terada, Yuhei Kogata, Hiroshi Sasaki, Satoshi Tsunetoh, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
International Journal of Molecular Sciences.2021; 22(17): 9369. CrossRef
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Pancreatology.2020; 20(3): 485. CrossRef
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Suad M. Abdirahman, Michael Christie, Adele Preaudet, Marie C. U. Burstroem, Dmitri Mouradov, Belinda Lee, Oliver M. Sieber, Tracy L. Putoczki
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Michael-Antony Lisio, Lili Fu, Alicia Goyeneche, Zu-hua Gao, Carlos Telleria
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Yoshiaki Maru, Naotake Tanaka, Makiko Itami, Yoshitaka Hippo
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Current Status of Patient-Derived Ovarian Cancer Models
Yoshiaki Maru, Yoshitaka Hippo
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Establishment of patient‐derived xenograft model in ovarian cancer and its influence factors analysis
Jianfa Wu, Yunxi Zheng, Qi Tian, Ming Yao, Xiaofang Yi
Journal of Obstetrics and Gynaecology Research.2019; 45(10): 2062. CrossRef
Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells
Ugo Testa, Eleonora Petrucci, Luca Pasquini, Germana Castelli, Elvira Pelosi
Medicines.2018; 5(1): 16. CrossRef

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Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2: Kyung Jin Eoh, Ji Eun Kim, Hyung Seok Park, Seung-Tae Lee, Ji Soo Park, Jung Woo Han, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Jae Hoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2018;50(3):917-925. Published online September 27, 2017; DOI: https://doi.org/10.4143/crt.2017.220

Abstract PDF Supplementary Material PubReader ePub

Purpose
Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS.
Materials and Methods
Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing.
Results
Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance.
Conclusion
Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

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Chalermkiat Kansuttiviwat, Pongtawat Lertwilaiwittaya, Ekkapong Roothumnong, Panee Nakthong, Peerawat Dungort, Chutima Meesamarnpong, Warisara Tansa-Nga, Khontawan Pongsuktavorn, Supakit Wiboonthanasarn, Warunya Tititumjariya, Nannipa Phuphuripan, Chittap
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Zheng Feng, Siyu Chen, Na An, Zhihui Xiu, Xingzhu Ju, Xiaojun Chen, Rui Bi, Jie Wang, Shida Zhu, Xiaohua Wu, Hao Wen
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Siddhartha Yadav, Fergus J. Couch, Susan M. Domchek
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Long Non-coding RNA HOXA11 Antisense Promotes Cell Proliferation and Invasion and Predicts Patient Prognosis in Serous Ovarian Cancer: Ga Won Yim, Hee Jung Kim, Lee Kyung Kim, Sang Wun Kim, Sunghoon Kim, Eun Ji Nam, Young Tae Kim; Cancer Res Treat. 2017;49(3):656-668. Published online October 11, 2016; DOI: https://doi.org/10.4143/crt.2016.263

Abstract PDF PubReader ePub

Purpose
The biological function of long non-coding RNAs (lncRNAs) is only partially understood; therefore, in this study, we investigated the expression of the novel HOXA11 antisense (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC).
Materials and Methods
HOXA11as expression was examined in 129 SOC tissue samples by real time reverse transcription polymerase chain reaction. Clinicopathological factors and patient survival were compared between the high (n=27) and low HOXA11as expression group (n=102). To investigate the role of HOXA11as in cell proliferation, invasion, and migration, HOXA11as expression in ovarian cancer cells was knocked down using RNA interference.
Results
HOXA11as expression in cancer tissue was 77-fold higher than that of noncancerous tissue (p < 0.05). Higher HOXA11as expression was significantly correlated with histological grade (p=0.017) and preoperative cancer antigen 125 (p=0.048). HOXA11as overexpression in SOC cells led to increased cell proliferation, invasion, and migration. Moreover, HOXA11as was associated with the expression of genes involved in cell invasion, migration, and epithelial-mesenchymal transition (EMT), including vascular endothelial growth factor, matrix metalloproteinase 9 (MMP-9), B-catenin, E-cadherin, Snail, Twist, and vimentin. Multivariate analysis revealed that HOXA11as was a prognostic factor of progressive disease and mortality (hazard ratio [HR], 1.730; p=0.043 and HR, 2.170; p=0.033, respectively). Progression-free and overall survival were significantly shorter in patients with high HOXA11as expression.
Conclusion
These findings highlight the clinical significance of HOXA11as to predicting the prognosis of SOC patients and suggest its potential in promoting tumor aggressiveness via regulation of vascular endothelial growth factor (VEGF), MMP-9, and EMT-related mechanisms.

Citations

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The Role of EMT-Related lncRNAs in Ovarian Cancer
Dimitra Ioanna Lampropoulou, Marios Papadimitriou, Christos Papadimitriou, Dimitrios Filippou, Georgia Kourlaba, Gerasimos Aravantinos, Maria Gazouli
International Journal of Molecular Sciences.2023; 24(12): 10079. CrossRef
LncRNAs and the Angiogenic Switch in Cancer: Clinical Significance and Therapeutic Opportunities
Peace Mabeta, Rodney Hull, Zodwa Dlamini
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Long non-coding RNA HOXA11-AS knockout inhibits proliferation and overcomes drug resistance in ovarian cancer
Yuwei Chen, Zhaolei Cui, Qiaoling Wu, Huihui Wang, Hongmei Xia, Yang Sun
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The role of altered long noncoding RNAs in overall survival of ovarian cancer: A systematic review and meta-analysis
Elahe Seyed Hosseini, Marziyeh Alizadeh Zarei, Hamed Haddad Kashani, Alireza Milajerdi, Zahra Zare Dehghanani, Hassan Hassani Bafrani, Hossein Nikzad
Pathology - Research and Practice.2021; 219: 153363. CrossRef
Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer
Karolina Seborova, Radka Vaclavikova, Lukas Rob, Pavel Soucek, Pavel Vodicka
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Long non-coding RNAs: A view to kill ovarian cancer
Alexey V. Zamaraev, Pavel I. Volik, Gennady T. Sukhikh, Gelina S. Kopeina, Boris Zhivotovsky
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2021; 1876(1): 188584. CrossRef
Long non-coding RNA CASC15 favors tumorigenesis and development of ovarian cancer via sponging miR-542-3p
Qiang LI, Wenjing LIU, Sumei LI, Su ZHANG
Panminerva Medica.2021;[Epub] CrossRef
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Selin Oncul, Paola Amero, Cristian Rodriguez-Aguayo, George A. Calin, Anil K. Sood, Gabriel Lopez-Berestein
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Soudeh Ghafouri-Fard, Mohammadhosein Esmaeili, Hamed Shoorei, Mohammad Taheri
Biomedicine & Pharmacotherapy.2020; 125: 110027. CrossRef
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Lin Deng, Ding-qing Feng, Bin Ling
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Sun-Ae Park, Lee Kyung Kim, Young Tae Kim, Tae-Hwe Heo, Hee Jung Kim
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lncRNA HOXA11-AS Promotes Proliferation and Migration via Sponging miR-155 in Hypopharyngeal Squamous Cell Carcinoma
Jianing Xu, Qiyu Bo, Xiang Zhang, Dapeng Lei, Jue Wang, Xinliang Pan
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics.2020; 28(3): 311. CrossRef
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Jin-yan Wang, Ai-qing Lu, Li-juan Chen
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Hui Xu, Jing-Fang Zheng, Cong-Zhe Hou, Yue Li, Pei-Shu Liu
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Qian Zhao, Conghong Fan
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Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils
Anquan Shang, Weiwei Wang, Chenzheng Gu, Chen Chen, Bingjie Zeng, Yibao Yang, Ping Ji, Junjun Sun, Junlu Wu, Wenying Lu, Zujun Sun, Dong Li
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Chu Zhang, Jie Liu, Yang Zhang, Chengyan Luo, Tong Zhu, Rongrong Zhang, Ruiqin Yao
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Shidai Mu, Lisha Ai, Fengjuan Fan, Chunyan Sun, Yu Hu
Cancer Cell International.2018;[Epub] CrossRef
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Lei Zhan, Jun Li, Bing Wei
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HOXA11 antisense long noncoding RNA (HOXA11‐AS): A promising lncRNA in human cancers
Cheng‐Wei Lu, Dan‐Dan Zhou, Tian Xie, Ji‐Long Hao, Om Prakash Pant, Cheng‐Bo Lu, Xiu‐Fen Liu
Cancer Medicine.2018; 7(8): 3792. CrossRef
Long noncoding RNA LINC00152 promotes cell proliferation through competitively binding endogenous miR‐125b with MCL‐1 by regulating mitochondrial apoptosis pathways in ovarian cancer
Puxiang Chen, Xiaolin Fang, Bing Xia, Yan Zhao, Qiaoyan Li, Xiaoying Wu
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Li Ning, Ying-chao Hu, Shu Wang, Jing-he Lang
Medicine.2018; 97(32): e11481. CrossRef
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Xiaojing Lin, Junjun Qiu, Keqin Hua
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RETRACTED ARTICLE: Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer
Haihai Liang, Xiaoguang Zhao, Chengyu Wang, Jian Sun, Yingzhun Chen, Guoyuan Wang, Lei Fang, Rui Yang, Mengxue Yu, Yunyan Gu, Hongli Shan
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Mei S Ong, Wanpei Cai, Yi Yuan, Hin C Leong, Tuan Z Tan, Asad Mohammad, Ming L You, Frank Arfuso, Boon C Goh, Sudha Warrier, Gautam Sethi, Nicholas S Tolwinski, Peter E Lobie, Celestial T Yap, Shing C Hooi, Ruby Y Huang, Alan P Kumar
British Journal of Pharmacology.2017; 174(24): 4684. CrossRef
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Na Li, Meilan Yang, Ke Shi, Wei Li
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Kyung Jin Eoh, Hee Jung Kim, Jung-Yun Lee, Eun Ji Nam, Sunghoon Kim, Sang Wun Kim, Young Tae Kim
Oncotarget.2017; 8(41): 70579. CrossRef

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Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients: Kyung Jin Eoh, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Jeongwoo Han, Jung-Yun Lee, Sang Wun Kim, Sunghoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2017;49(2):408-415. Published online July 27, 2016; DOI: https://doi.org/10.4143/crt.2016.135

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type).
Materials and Methods
We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status.
Results
Thirty-seven (37/116, 31.9%) BRCA1/2 mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively).
Conclusion
Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.

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Journal of Clinical Pathology.2023; 76(8): 510. CrossRef
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Yazhuo Wang, Na Li, Yanan Ren, Jing Zhao
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Cláudia Caeiro, Inês Leão, Inês Oliveira, Isabel Sousa, Teresa André
Advances in Therapy.2022; 39(11): 5289. CrossRef
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Shira Peleg Hasson, Dov Hershkovitz, Lyri Adar, Miriam Brezis, Eliya Shachar, Rona Aks, Lee Galmor, Yuval Raviv, Shira Ben Neriah, Ofer Merimsky, Edmond Sabo, Ido Wolf, Tamar Safra
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Sherif B. Elsherif, Priya R. Bhosale, Chandana Lall, Christine O. Menias, Malak Itani, Kristina A. Butler, Dhakshinamoorthy Ganeshan
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Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer
Kyung Jin Eoh, Hye Min Kim, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Young Tae Kim, Eun Ji Nam
BMC Cancer.2020;[Epub] CrossRef
Association of Germline Variants in Human DNA Damage Repair Genes and Response to Adjuvant Chemotherapy in Resected Pancreatic Ductal Adenocarcinoma
Haijie Hu, Yayun Zhu, Ning Pu, Richard A. Burkhart, William Burns, Daniel Laheru, Lei Zheng, Jin He, Michael G. Goggins, Jun Yu
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Hyeong In Ha, Jin-Sun Ryu, Hyoeun Shim, Sun-Young Kong, Myong Cheol Lim
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Anastasis Oulas, George Minadakis, Margarita Zachariou, George M. Spyrou
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Se Ik Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong-Sang Song
Journal of Ovarian Research.2019;[Epub] CrossRef
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Mohammad Mirza-Aghazadeh-Attari, Caspian Ostadian, Amir Ata Saei, Ainaz Mihanfar, Saber Ghazizadeh Darband, Shirin Sadighparvar, Mojtaba Kaviani, Hossein Samadi Kafil, Bahman Yousefi, Maryam Majidinia
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Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review
Byung Su Kwon, Jung Mi Byun, Hyun Joo Lee, Dae Hoon Jeong, Tae Hwa Lee, Kyung-Hwa Shin, Dong Soo Suh, Ki Hyung Kim
Cancer Research and Treatment.2019; 51(3): 941. CrossRef
Prevalence and oncologic outcomes of BRCA1/2 mutation and variant of unknown significance in epithelial ovarian carcinoma patients in Korea
Jun Hyeong Seo, Soo Young Jeong, Myeong Seon Kim, Jun Hyeok Kang, E Sun Paik, Yoo-Young Lee, Tae-Joong Kim, Jeong-Won Lee, Byoung-Gie Kim, Duk-Soo Bae, Chel Hun Choi
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Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer
Min Chul Choi, Ja-Hyun Jang, Sang Geun Jung, Hyun Park, Won Duk Joo, Seung Hun Song, Chan Lee, Je Ho Lee
International Journal of Gynecological Cancer.2018; 28(2): 308. CrossRef
Prevalence of germline BRCA mutations among women with carcinoma of the peritoneum or fallopian tube
Min Chul Choi, Jin-Sik Bae, Sang Geun Jung, Hyun Park, Won Duk Joo, Seung Hun Song, Chan Lee, Ji-Ho Kim, Ki-Chan Lee, Sunghoon Lee, Je Ho Lee
Journal of Gynecologic Oncology.2018;[Epub] CrossRef
Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2
Kyung Jin Eoh, Ji Eun Kim, Hyung Seok Park, Seung-Tae Lee, Ji Soo Park, Jung Woo Han, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Jae Hoon Kim, Young Tae Kim, Eun Ji Nam
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BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic‐related mutations in BRCA1 associated with an increased risk of ovarian cancer
Tingyan Shi, Pan Wang, Caixia Xie, Sheng Yin, Di Shi, Congchong Wei, Wenbin Tang, Rong Jiang, Xi Cheng, Qingyi Wei, Qing Wang, Rongyu Zang
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448 Download
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Endometrial Stromal Sarcomas: A Retrospective Analysis of 28 Patients, Single Center Experience for 20 Years: Eun Ji Nam, Jae Wook Kim, Dae Woo Lee, Si Young Jang, Jong Wook Hong, Young Tae Kim, Jae Hoon Kim, Sunghoon Kim, Sang Wun Kim; Cancer Res Treat. 2008;40(1):6-10. Published online March 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.1.6

Abstract PDF PubReader ePub

Purpose

The aim of this study was to evaluate the behavior of endometrial stromal sarcomas (ESSs) in relation to their clinical and pathogenic features, and to determine the optimal treatment strategy.

Materials and Methods

A retrospective analysis was performed involving 28 patients with histologic-proven ESSs treated at our institution between 1987 and 2006.

Results

The median follow-up was 54.7±63.1 months and the 5-year survival rate was 82.0%. Twenty-two (81.5%) and 5 patients (18.5%) had low- and high-grade disease, respectively. Univariate analysis revealed that the histologic grades, based on mitotic count, were associated with longer survival (p=0.004). However, among those patients with low-grade tumors, 5/20 patients (25%) had a recurrence and 2/21 patients (9.5%) had distant metastasis during the follow-up period. With the exception of 2 patients, 26 patients with ESSs underwent hysterectomy as primary treatment. Adjuvant treatment after surgery was administered to 14/26 patients (53.8%). Hormone therapy with progesterone, chemotherapy, and/or radiotherapy did not influence overall survival. However, the postoperative adjuvant therapy group, regardless of the treatment modality, was associated with relatively increased overall survival when compared to the surgery only group (p=0.054).

Conclusions

The preoperative differential diagnosis of ESSs from other benign gynecologic diseases is often difficult. We recommend adjuvant therapy be administered after hysterectomy in patients with ESS to prevent recurrence or distant metastasis.

Citations

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