Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Combined High-Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-institutional Cohort Study: Jung Ho Im, Jeong Il Yu, Tae Hyun Kim, Tae Gyu Kim, Jun Won Kim, Jinsil Seong; Cancer Res Treat. 2024;56(3):838-846. Published online January 2, 2024; DOI: https://doi.org/10.4143/crt.2023.886

Abstract PDF Supplementary Material PubReader ePub: Purpose
The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC.
Materials and Methods
Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model.
Results
The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05).
Conclusion
Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.

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The Oncologic Implications of Tumor Multiplicity in Intrahepatic Cholangiocarcinoma: Its Prognostic Value Might Be Underestimated: So Jeong Yoon, Sunghae Park, Hongbeom Kim, Sang Hyun Shin, Jin Seok Heo, Jinsoo Rhu, Gyu-Seong Choi, Jong Man Kim, Jae-Won Joh, In Woong Han; Cancer Res Treat. 2023;55(3):948-955. Published online February 27, 2023; DOI: https://doi.org/10.4143/crt.2023.290

Abstract PDF PubReader ePub

Purpose
In the latest staging system of the American Joint Committee on Cancer for intrahepatic cholangiocarcinoma (IHCCC), solitary tumors with vascular invasion and multiple tumors are grouped together as T2. However, recent studies report that multifocal IHCCC has a worse prognosis than a single lesion. This study aimed to investigate the risk factors for IHCCC and explore the prognostic significance of multiplicity after surgical resection.
Materials and Methods
A total of 257 patients underwent surgery for IHCCC from 2010 to 2019 and the clinicopathological data were retrospectively reviewed. Risk factor analysis was performed to identify variables associated with survival after resection. Survival outcomes were compared between patients with solitary and multiple tumors.
Results
In multivariable analysis, the presence of preoperative symptoms, tumor size, lymph node ratio, multiplicity, and tumor differentiation were identified as risk factors for survival. Among 82 patients with T2, overall survival was significantly longer in patients with solitary tumors (sT2) than in those with multiple tumors (mT2) (p=0.017). Survival was compared among patients with stage II-sT2, stage II-mT2, and stage III. The stage II-sT2 group showed prolonged survival when compared with stage II-mT2 or stage III. Survivals of stage II-mT2 and stage III patients were not statistically different.
Conclusion
Tumor multiplicity was an independent risk factor for overall survival of IHCCC after surgical resection. Patients with multiple tumors showed poorer survival than patients with a single tumor. The oncologic significance of multiplicity in IHCCC should be reappraised and reflected in the next staging system update.

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Perihilar and Intrahepatic Cholangiocarcinoma after Resection: Clinicopathological Characteristics, Outcomes, and Implications for Addition of Chemoradiotherapy
Amar Mukund, Namita Sharma, Ankur Jindal, Archana Sharma, Ajay Gupta, Guresh Kumar, Archana Rastogi, Puja Sahai, Nilesh S Patil, Nihar Mohapatra, Karthika Rudrakumar, Viniyendra Pamecha, Hanuman P Yadav
Euroasian journal of hepato-gastroenterology.2024; 14(2): 134. CrossRef

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Long Non-coding RNA CASC15 Promotes Intrahepatic Cholangiocarcinoma Possibly through Inducing PRDX2/PI3K/AKT Axis: Yuan Zhang, Lufei Zhang, Sinan Lu, Yucheng Xiang, Cheng Zeng, Tianyu He, Yuan Ding, Weilin Wang; Cancer Res Treat. 2021;53(1):184-198. Published online October 5, 2020; DOI: https://doi.org/10.4143/crt.2020.192

Abstract PDF Supplementary Material PubReader ePub

Purpose
Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear.
Materials and Methods
Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry.
Results
CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway.
Conclusion
CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.

Citations

Citations to this article as recorded by

Exploring the mechanism of LncRNA CASC15 affecting hepatocellular carcinoma through miRNA
Qingshan Cai, Dongyang Wu, Yueling Shen, Shudong Li, Liyou Liu, Dong Liu, Yong Li, Xiaonan Chen, Limin Wang, Jianxing Zheng
Medicine.2024; 103(5): e35859. CrossRef
The effect of genetics and biochemistry on the pathogenesis of cholangiocarcinoma
Mete Ucdal, Ayse Burus, Basak Celtikci
International Journal of Hepatobiliary and Pancreatic Diseases.2024; 14(2): 1. CrossRef
Interplay between lncRNAs and the PI3K/AKT signaling pathway in the progression of digestive system neoplasms (Review)
Xiaoyu Zhang, Lei Shi, Mengzhen Xing, Chunjing Li, Fengjun Ma, Yuning Ma, Yuxia Ma
International Journal of Molecular Medicine.2024;[Epub] CrossRef
A review on the role of ncRNAs in the pathogenesis of cholangiocarcinoma
Soudeh Ghafouri-Fard, Arash Safarzadeh, Bashdar Mahmud Hussen, Mohammad Taheri, Majid Samsami
International Journal of Biological Macromolecules.2023; 225: 809. CrossRef
A Novel CASC15-ALK and TFG-ROS1 Fusion Observed in Uterine Inflammatory Myofibroblastic Tumor
Bin Chang, Zhe Wang, Min Ren, Qianlan Yao, Lu Zhao, Xiaoyan Zhou
International Journal of Gynecological Pathology.2023; 42(5): 451. CrossRef
Development and validation of combined Ki67 status prediction model for intrahepatic cholangiocarcinoma based on clinicoradiological features and MRI radiomics
Xianling Qian, Changwu Zhou, Fang Wang, Xin Lu, Yunfei Zhang, Lei Chen, Mengsu Zeng
La radiologia medica.2023; 128(3): 274. CrossRef
Non-Coding RNA in Cholangiocarcinoma: An Update
Jiehan Li, Haolin Bao, Ziyue Huang, Zixin Liang, Ning Lin, Chunjie Ni, Yi Xu
Frontiers in Bioscience-Landmark.2023;[Epub] CrossRef
A study of the prognostic value of long non-coding RNA CASC15 in human solid tumors utilizing The Cancer Genome Atlas (TCGA) datasets and a meta-analysis
Weiwei Chen, Wenqi Qian, Jun Nie, Mintao Dai
Clinical and Experimental Medicine.2022;[Epub] CrossRef
Long Non-Coding RNAs as Molecular Biomarkers in Cholangiocarcinoma
Yanhua Wu, Khizar Hayat, Yufei Hu, Jianfeng Yang
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Brusatol suppresses the growth of intrahepatic cholangiocarcinoma by PI3K/Akt pathway
Ziyan Chen, Bangjie He, Jungang Zhao, Jiacheng Li, Yifeng Zhu, Leilei Li, Wenming Bao, Jiuyi Zheng, Haitao Yu, Gang Chen
Phytomedicine.2022; 104: 154323. CrossRef
Cystic angiomatosis in children: clinical experience and review of literature
Wen Chao Li, Li Liu, Zhen Dong Wang, Hui Chen, Guang Liu, Zhi Chun Feng
World Journal of Surgical Oncology.2022;[Epub] CrossRef
A Study on Mesoporous Silica Loaded With Novel Photosensitizers HCE6 and Oxaliplatin for the Treatment of Cholangiocarcinoma
Pei-Jian Zhang, Meng-Dong Liu, Fang-Yong Fan, Ke-Xia Liu
Frontiers in Oncology.2021;[Epub] CrossRef
LncRNA CASC15 promotes the proliferation of papillary thyroid carcinoma cells by regulating the miR-7151–5p/WNT7A axis
Dongfang Bai, Chong Guo, Aimin Wang, Guolong Pang, Jing Gao, Chuan Wang, Dapeng Zhao, Jie Yang, Jianmin Ren
Pathology - Research and Practice.2021; 225: 153561. CrossRef
LncRNA CASC15 Promotes Cerebral Ischemia/Reperfusion Injury via miR-338-3p/ETS1 Axis in Acute Ischemic Stroke
Chen Chen, Linjing Wang, Li Wang, Qi Liu, Chunying Wang
International Journal of General Medicine.2021; Volume 14: 6305. CrossRef
Protein profiling reveals potential isomiR-associated cross-talks among RNAs in cholangiocarcinoma
Li Guo, Yuyang Dou, Yifei Yang, Shiqi Zhang, Yihao Kang, Lulu Shen, Lihua Tang, Yaodong Zhang, Changxian Li, Jun Wang, Tingming Liang, Xiangcheng Li
Computational and Structural Biotechnology Journal.2021; 19: 5722. CrossRef

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An Integrated Nomogram Combining Clinical Factors and Microtubule-Associated Protein 1 Light Chain 3B Expression to Predict Postoperative Prognosis in Patients with Intrahepatic Cholangiocarcinoma: Liang Chen, Hongyuan Fu, Tongyu Lu, Jianye Cai, Wei Liu, Jia Yao, Jinliang Liang, Hui Zhao, Jiebin Zhang, Jun Zheng, Yingcai Zhang, Yang Yang; Cancer Res Treat. 2020;52(2):469-480. Published online October 7, 2019; DOI: https://doi.org/10.4143/crt.2019.423

Abstract PDF Supplementary Material PubReader ePub

Purpose
Microtubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy, which is associated with the progression of carcinoma. Yet, it is still unclear whether LC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aim to explore the predictive value of LC3B on prognosis of ICC, and to establish a novel and available nomogram to predict relapse-free survival (RFS) and overall survival (OS) for these patients after curative-intent hepatectomy.
Materials and Methods
From August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the Third Affiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolled patients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry.
Results
The 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariate Cox regression analysis, independent risk factors for 5-year OS were cancer antigen 125, microvascular invasion, LC3B expression and lymph node metastasis. Except for the above 4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factors for 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and 0.747, respectively.
Conclusion
The nomograms based on LC3B can be considered as effective models to predict postoperative survival for ICC patients.

Citations

Citations to this article as recorded by

Lymph node metastasis of intrahepatic cholangiocarcinoma: the present and prospect of detection and dissection
Ruoyu Zhang, Yunfei Tan, Mei Liu, Liming Wang
European Journal of Gastroenterology & Hepatology.2024; 36(12): 1359. CrossRef
Active Autophagy Is Associated with Favorable Outcome in Patients with Surgically Resected Cholangiocarcinoma
Katrin Bankov, Falko Schulze, Steffen Gretser, Henning Reis, Nada Abedin, Fabian Finkelmeier, Jörg Trojan, Stefan Zeuzem, Andreas A. Schnitzbauer, Dirk Walter, Peter J. Wild, Maximilian N. Kinzler
Cancers.2023; 15(17): 4322. CrossRef
The role and implication of autophagy in cholangiocarcinoma
Hayat Khizar, Yufei Hu, Yanhua Wu, Jianfeng Yang
Cell Death Discovery.2023;[Epub] CrossRef
Immunogenomics of cholangiocarcinoma
Virag Gehl, Colm J. O’Rourke, Jesper B. Andersen
Hepatology.2023;[Epub] CrossRef
Multiparametric MRI‐Based Radiomic Signature for Preoperative Evaluation of Overall Survival in Intrahepatic Cholangiocarcinoma After Partial Hepatectomy
Yang Yang, Xianlun Zou, Wei Zhou, Guanjie Yuan, Daoyu Hu, Dong Kuang, Yaqi Shen, Qingguo Xie, Qingpeng Zhang, Xuemei Hu, Zhen Li
Journal of Magnetic Resonance Imaging.2022; 56(3): 739. CrossRef
A Myeloid Signature-Based Nomogram Predicts the Postoperative Recurrence of Intrahepatic Cholangiocarcinoma
Jing Liang, Hui Zhou, Xiang-Qi Huang, Yan-Fei Liu, Lei Zhang, Dan He, Yongmei Cui, Jinrui Guo, Kunpeng Hu, Chong Wu
Frontiers in Molecular Biosciences.2021;[Epub] CrossRef
Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma
Hector Perez-Montoyo
Cells.2020; 9(3): 614. CrossRef

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