Cancer Research and Treatment

Original Articles

Genitourinary cancer

Next-generation Proteomics-Based Discovery, Verification, and Validation of Urine Biomarkers for Bladder Cancer Diagnosis: Jungyo Suh, Dohyun Han, Ja Hyeon Ku, Hyeon Hoe Kim, Cheol Kwak, Chang Wook Jeong; Cancer Res Treat. 2022;54(3):882-893. Published online October 9, 2021; DOI: https://doi.org/10.4143/crt.2021.642

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to identify, verify, and validate a multiplex urinary biomarker-based prediction model for diagnosis and surveillance of urothelial carcinoma of bladder, using high-throughput proteomics methods.
Materials and Methods
Label-free quantification of data-dependent and data-independent acquisition of 12 and 24 individuals was performed in each of the discovery and verification phases using mass spectrometry, simultaneously using urinary exosome and proteins. Based on five scoring system based on proteomics data and statistical methods, we selected eight proteins. Enzyme-linked immunosorbent assay on urine from 120 patients with bladder mass lesions used for validation. Using multivariable logistic regression, we selected final candidate models for predicting bladder cancer.
Results
Comparing the discovery and verification cohorts, 38% (50/132 exosomal differentially expressed proteins [DEPs]) and 44% (109/248 urinary DEPs) are consistent at statistically significance, respectively. The 20 out of 50 exosome proteins and 27 out of 109 urinary proteins were upregulated in cancer patients. From eight selected proteins, we developed two diagnostic models for bladder cancer. The area under the receiver operating characteristic curve (AUROC) of two models were 0.845 and 0.842, which outperformed AUROC of urine cytology.
Conclusion
The results showed that the two diagnostic models developed here were more accurate than urine cytology. We successfully developed and validated a multiplex urinary protein-based prediction, which will have wide applications for the rapid diagnosis of urothelial carcinoma of the bladder. External validation for this biomarker panel in large population is required.

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A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes
Bingrui Li, Fernanda G Kugeratski, Raghu Kalluri
eLife.2024;[Epub] CrossRef
A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes
Bingrui Li, Fernanda G Kugeratski, Raghu Kalluri
eLife.2024;[Epub] CrossRef
Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer
Qi Chang, Yongqiang Chen, Jianjian Yin, Tao Wang, Yuanheng Dai, Zixin Wu, Yufeng Guo, Lingang Wang, Yufen Zhao, Hang Yuan, Dongkui Song, Lirong Zhang
Journal of Proteome Research.2024; 23(6): 2241. CrossRef
Construction of noninvasive prognostic model of bladder cancer patients based on urine proteomics and screening of natural compounds
Shun Wan, Jinlong Cao, Siyu Chen, Jianwei Yang, Huabin Wang, Chenyang Wang, Kunpeng Li, Li Yang
Journal of Cancer Research and Clinical Oncology.2023; 149(1): 281. CrossRef
Extracellular Vesicles as Potential Bladder Cancer Biomarkers: Take It or Leave It?
Ana Teixeira-Marques, Catarina Lourenço, Miguel Carlos Oliveira, Rui Henrique, Carmen Jerónimo
International Journal of Molecular Sciences.2023; 24(7): 6757. CrossRef
Advances in the application of label‐free quantitative proteomics techniques in malignancy research
Xiao Meng, Dong Liu, Yan Guan
Biomedical Chromatography.2023;[Epub] CrossRef
Off the fog to find the optimal choice: Research advances in biomarkers for early diagnosis and recurrence monitoring of bladder cancer
Jiaxin Zhao, Jinming Li, Rui Zhang
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2023; 1878(4): 188926. CrossRef
An overview of metabolomic and proteomic profiling in bipolar disorder and its clinical value
Henrique Caracho Ribeiro, Flávia da Silva Zandonadi, Alessandra Sussulini
Expert Review of Proteomics.2023; 20(11): 267. CrossRef
Proteome and immune responses of extracellular vesicles derived from macrophages infected with the periodontal pathogen Tannerella forsythia
Younggap Lim, Hyun Young Kim, Dohyun Han, Bong‐Kyu Choi
Journal of Extracellular Vesicles.2023;[Epub] CrossRef
A Liquid Biopsy in Bladder Cancer—The Current Landscape in Urinary Biomarkers
Milena Matuszczak, Adam Kiljańczyk, Maciej Salagierski
International Journal of Molecular Sciences.2022; 23(15): 8597. CrossRef
Next-generation proteomics of serum extracellular vesicles combined with single-cell RNA sequencing identifies MACROH2A1 associated with refractory COVID-19
Takahiro Kawasaki, Yoshito Takeda, Ryuya Edahiro, Yuya Shirai, Mari Nogami-Itoh, Takanori Matsuki, Hiroshi Kida, Takatoshi Enomoto, Reina Hara, Yoshimi Noda, Yuichi Adachi, Takayuki Niitsu, Saori Amiya, Yuta Yamaguchi, Teruaki Murakami, Yasuhiro Kato, Tak
Inflammation and Regeneration.2022;[Epub] CrossRef

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Effects of Aspirin, Nonsteroidal Anti-inflammatory Drugs, Statin, and COX2 Inhibitor on the Developments of Urological Malignancies: A Population-Based Study with 10-Year Follow-up Data in Korea: Minyong Kang, Ja Hyeon Ku, Cheol Kwak, Hyeon Hoe Kim, Chang Wook Jeong; Cancer Res Treat. 2018;50(3):984-991. Published online October 27, 2017; DOI: https://doi.org/10.4143/crt.2017.248

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to determine the impact of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), statin, and cyclooxygenase 2 (COX-2) inhibitor on the development of kidney, prostate, and urothelial cancers by analyzing the Korean National Health Insurance Service–National Sample Cohort (NHIS-NSC) database.
Materials and Methods
Among a representative sample cohort of 1,025,340 participants in NHIS-NSC database in 2002, we extracted data of 799,850 individuals who visited the hospital more than once, and finally included 321,122 individuals aged 40 and older. Following a 1-year washout period between 2002 and 2003, we analyzed 143,870 (male), 320,861 and 320,613 individuals for evaluating the risk of prostate cancer, kidney cancer and urothelial cancer developments, respectively, during 10-year follow-up periods between 2004 and 2013. The medication group consisted of patients prescribed these drugs more than 60% of the time in 2003. To adjustfor various parameters of the patients, a multivariate Cox regression model was adopted.
Results
During 10-year follow-up periods between 2004 and 2013, 9,627 (6.7%), 1,107 (0.4%), and 2,121 (0.7%) patients were diagnosed with prostate cancer, kidney cancer, and urothelial cancer, respectively. Notably, multivariate analyses revealed that NSAIDs significantly increased the risk of prostate cancer (hazard ratio [HR], 1.35). Also, it was found that aspirin (HR, 1.28) and statin (HR, 1.55) elevated the risk of kidney cancer. No drugs were associated with the risk of urothelial cancer.
Conclusion
In sum, our study provides the valuable information for the impact of aspirin, NSAID, statin, and COX-2 inhibitor on the risk of prostate, kidney, and urothelial cancer development and its survival outcomes.

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Association between Statin Use and Clinical Outcomes in Patients with De Novo Metastatic Prostate Cancer: A Propensity Score-weighted Analysis
Tzu Shuang Chen, Hui Ying Liu, Yin Lun Chang, Yao Chi Chuang, Yen Ta Chen, Yu Li Su, Chun Chieh Huang, Yen Ting Wu, Hung Jen Wang, Hao Lun Luo
The World Journal of Men's Health.2024; 42(3): 630. CrossRef
Establishment of Prospective Registry of Active Surveillance for Prostate Cancer: The Korean Urological Oncology Society Database
Gyoohwan Jung, Jung Kwon Kim, Seong Soo Jeon, Jae Hoon Chung, Cheol Kwak, Chang Wook Jeong, Hanjong Ahn, Jae Young Joung, Tae Gyun Kwon, Sung Woo Park, Seok-Soo Byun
The World Journal of Men's Health.2023; 41(1): 110. CrossRef
Evaluation of statin use and renal cell carcinoma risk identifies sex-specific associations with RCC subtypes
Irmina Maria Michalek, Rebecca E. Graff, Alejandro Sanchez, Toni K. Choueiri, Eunyoung Cho, Mark A. Preston, Kathryn M. Wilson
Acta Oncologica.2023; 62(9): 988. CrossRef
Effect of aspirin on incidence, recurrence, and mortality in prostate cancer patients: integrating evidence from randomized controlled trials and real-world studies
Shaodi Ma, Weihang Xia, Birong Wu, Chenyu Sun, Yuemeng Jiang, Haixia Liu, Scott Lowe, Zhen Zhou, Peng Xie, Juan Gao, Linya Feng, Xianwei Guo, Guangbo Qu, Yehuan Sun
European Journal of Clinical Pharmacology.2023; 79(11): 1475. CrossRef
Evidence on Statins, Omega-3, and Prostate Cancer: A Narrative Review
Hwanik Kim, Jung Kwon Kim
The World Journal of Men's Health.2022; 40(3): 412. CrossRef
The Association of Prediagnostic Statin Use with Aggressive Prostate Cancer from the Multiethnic Cohort Study
Fei Chen, Peggy Wan, Lynne R. Wilkens, Loïc Le Marchand, Christopher A. Haiman
Cancer Epidemiology, Biomarkers & Prevention.2022; 31(5): 999. CrossRef
Aspirin and the risk of nondigestive tract cancers: An updated meta‐analysis to 2019
Claudia Santucci, Silvano Gallus, Marco Martinetti, Carlo La Vecchia, Cristina Bosetti
International Journal of Cancer.2021; 148(6): 1372. CrossRef
Association between depression and risk of Parkinson's disease in South Korean adults
Wonjeong Jeong, Hyunkyu Kim, Jae Hong Joo, Sung-In Jang, Eun-Cheol Park
Journal of Affective Disorders.2021; 292: 75. CrossRef
Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment
Bo Fan, Alradhi Mohammed, Yuanbin Huang, Hong Luo, Hongxian Zhang, Shenghua Tao, Weijiao Xu, Qian Liu, Tao He, Huidan Jin, Mengfan Sun, Man Sun, Zhifei Yun, Rui Zhao, Guoyu Wu, Xiancheng Li
Frontiers in Oncology.2021;[Epub] CrossRef
Association Between Genetically Proxied Lipid-Lowering Drug Targets and Renal Cell Carcinoma: A Mendelian Randomization Study
Luyang Liu, Chao Sheng, Zhangyan Lyu, Hongji Dai, Kexin Chen
Frontiers in Nutrition.2021;[Epub] CrossRef
Associations of low-dose aspirin or other NSAID use with prostate cancer risk in the Danish Diet, Cancer and Health Study
Charlotte Skriver, Christian Dehlendorff, Michael Borre, Klaus Brasso, Signe Benzon Larsen, Anne Tjønneland, Anton Pottegård, Jesper Hallas, Henrik Toft Sørensen, Søren Friis
Cancer Causes & Control.2020; 31(2): 139. CrossRef
Impact of Concomitant Medication Use and Immune-Related Adverse Events on Response to Immune Checkpoint Inhibitors
Shipra Gandhi, Manu Pandey, Nischala Ammannagari, Chong Wang, Mark J Bucsek, Lamya Hamad, Elizabeth Repasky, Marc S Ernstoff
Immunotherapy.2020; 12(2): 141. CrossRef
Risks of solid cancers in elderly persons with osteoarthritis or ankylosing spondylitis
Michael M Ward, Sara Alehashemi
Rheumatology.2020; 59(12): 3817. CrossRef
Complex roles of the old drug aspirin in cancer chemoprevention and therapy
Hui Hua, Hongying Zhang, Qingbin Kong, Jiao Wang, Yangfu Jiang
Medicinal Research Reviews.2019; 39(1): 114. CrossRef
Establishment of the Seoul National University Prospectively Enrolled Registry for Genitourinary Cancer (SUPER-GUC): A prospective, multidisciplinary, bio-bank linked cohort and research platform
Chang Wook Jeong, Jungyo Suh, Hyeong Dong Yuk, Bum Sik Tae, Miso Kim, Bhumsuk Keam, Jin Ho Kim, Sang Youn Kim, Jeong Yeon Cho, Seung Hyup Kim, Kyung Chul Moon, Gi Jeong Cheon, Ja Hyeon Ku, Hyeon Hoe Kim, Cheol Kwak
Investigative and Clinical Urology.2019; 60(4): 235. CrossRef
The impact of acute inflammation on progression and metastasis in pancreatic cancer animal model
Keun Soo Ahn, Ji Yeon Hwang, Ho-Seong Han, Sang Tae Kim, Ilseon Hwang, Young-Ok Chun
Surgical Oncology.2018; 27(1): 61. CrossRef
Prostate cancer multifocality, the index lesion, and the microenvironment
Rafael R. Tourinho-Barbosa, Jean de la Rosette, Rafael Sanchez-Salas
Current Opinion in Urology.2018; 28(6): 499. CrossRef
Intake of Non-steroidal Anti-inflammatory Drugs and the Risk of Prostate Cancer: A Meta-Analysis
Zhenhua Shang, Xue Wang, Hao Yan, Bo Cui, Qi Wang, Jiangtao Wu, Xin Cui, Jin Li, Tongwen Ou, Kun Yang
Frontiers in Oncology.2018;[Epub] CrossRef

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Conditional Survival and Associated Prognostic Factors in Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy: A Retrospective Study at a Single Institution: Minyong Kang, Hyung Suk Kim, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, Ja Hyeon Ku; Cancer Res Treat. 2016;48(2):621-631. Published online September 9, 2015; DOI: https://doi.org/10.4143/crt.2015.220

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study is to evaluate the changes of conditional survival (CS) probabilities and to identify the prognostic parameters that significantly affect CS over time post-surgery in upper tract urothelial carcinoma (UTUC) patients. Materials and Methods A total of 330 patients were examined in the final analysis. Primary end point was conditional cancer-specific survival (CSS), overall survival (OS), and intravesical recurrence-free survival (IVRFS) after surgery. The Kaplan-Meier method was used for calculation of CS. Cox regression hazard ratio model was used to determine the predictors of CS.
Results
UTUC patients who had already survived 5 years after radical nephroureterectomy had a more favorable CS probability in all given survivorships compared to those with shorter survival times. Patients with unfavorable pathologic features showed a higher increment of 5-year conditional CSS and OS compared to their counterparts. For 5-year conditional CSS, several factors, including high-grade tumor, lymphovascular invasion, and tumor location showed significant association with risk elevation over time. Only age remained as a predictor of 5-year conditional OS with increased risk in all given survivorships. For 5-year IVRFS, no variables remained as significant predictive factors over time after surgery. Conclusion Our study provides valuable information for practical survival estimation and relevant prognostic factors for patients with UTUC after surgery.

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Adjuvant Chemotherapy after Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma with Variant Histology: A Systematic Review and Meta-Analysis of Survival Outcomes
Jinhyung Jeon, Jae Heon Kim, Jee Soo Ha, Won Jae Yang, Kang Su Cho, Do Kyung Kim
Urologia Internationalis.2024; 108(4): 339. CrossRef
Dynamic estimates of survival in oncocytic cell carcinoma of the thyroid
Yang Shi, Yuenan Zheng, Hao Zhang, Wenwu Dong, Ping Zhang
Discover Oncology.2023;[Epub] CrossRef
Factors Predicting Oncological Outcomes of Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma in Taiwan
I-Hsuan Alan Chen, Chao-Hsiang Chang, Chi-Ping Huang, Wen-Jeng Wu, Ching-Chia Li, Chung-Hsin Chen, Chao-Yuan Huang, Chi-Wen Lo, Chih-Chin Yu, Chung-You Tsai, Wei-Che Wu, Jen-Shu Tseng, Wun-Rong Lin, Yuan-Hong Jiang, Yu-Khun Lee, Yeong-Chin Jou, Ian-Seng C
Frontiers in Oncology.2022;[Epub] CrossRef
A retrospective multicenter comparison of conditional cancer-specific survival between laparoscopic and open radical nephroureterectomy in locally advanced upper tract urothelial carcinoma
Sung Han Kim, Mi Kyung Song, Ja Hyeon Ku, Seok Ho Kang, Byong Chang Jeong, Bumsik Hong, Ho Kyung Seo, Isaac Yi Kim
PLOS ONE.2021; 16(10): e0255965. CrossRef
Contemporary conditional cancer‐specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract
Giuseppe Rosiello, Carlotta Palumbo, Sophie Knipper, Angela Pecoraro, Stefano Luzzago, Marina Deuker, Francesco A. Mistretta, Zhe Tian, Nicola Fossati, Andrea Gallina, Francesco Montorsi, Shahrokh F. Shariat, Fred Saad, Alberto Briganti, Pierre I. Karakie
Journal of Surgical Oncology.2020; 121(7): 1154. CrossRef
Dynamic evaluation of conditional survival in patients with oral squamous cell carcinoma after surgical resection: A large-scale prospective study
Lingjun Yan, Fa Chen, Lin Chen, Jing Lin, Qing Chen, Xiaodan Bao, Yu Qiu, Lisong Lin, Xiaoyan Zheng, Lizhen Pan, Jing Wang, Zhijian Hu, Fengqiong Liu, Baochang He, Bin Shi
Oral Oncology.2020; 104: 104639. CrossRef
Gender Is a Significant Prognostic Factor for Upper Tract Urothelial Carcinoma: A Large Hospital-Based Cancer Registry Study in an Endemic Area
Chun-Chieh Huang, Yu-Li Su, Hao-Lun Luo, Yen-Ta Chen, Terence T. Sio, Hsuan-Chih Hsu, Chia-Hsuan Lai
Frontiers in Oncology.2019;[Epub] CrossRef
Prognostic Factors of Overall Survival in Upper Urinary Tract Carcinoma: A Systematic Review and Meta-analysis
Fausto Petrelli, Mohamed Ismail Yasser Hussein, Ivano Vavassori, Sandro Barni
Urology.2017; 100: 9. CrossRef
The Conditional Survival with Time of Intravesical Recurrence of Upper Tract Urothelial Carcinoma
Keisuke Shigeta, Eiji Kikuchi, Masayuki Hagiwara, Toshiyuki Ando, Ryuichi Mizuno, Takayuki Abe, Shuji Mikami, Akira Miyajima, Ken Nakagawa, Mototsugu Oya
Journal of Urology.2017; 198(6): 1278. CrossRef
Conditional survival in patients with gallbladder cancer
Yi-Jun Kim, Kyubo Kim
Chinese Journal of Cancer.2017;[Epub] CrossRef

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Prognosis of metastatic renal cell carcinoma: Won Hee Park, Hyeon Hoe Kim, Eun Sik Lee, Chongwook Lee; J Korean Cancer Assoc. 1992;24(1):160-167.

Abstract PDF: No abstract available.

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T1 bladder tumor: a heterogeneous and potentially dangerous group: Hyeon Hoe Kim, Chongwook Lee; J Korean Cancer Assoc. 1991;23(4):843-852.

Abstract PDF: No abstract available.

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Urothelial tumors of the upper urinary tract: Eun Sik Lee, Hyeon Hoe Kim, Kyung Joon Min, Moon Soo Park, Chongwook Lee; J Korean Cancer Assoc. 1991;23(4):828-834.

Abstract PDF: No abstract available.

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Methotrexate , Vinblastine , Doxorubicin and Cisplatin: Jin Soo Chung, Hyeon Hoe Kim, Chong Wook Lee; J Korean Cancer Assoc. 1994;26(4):618-626.

Abstract PDF: A study was performed to evaluated the effect of M-VAC(methotrexate, vinblastine, doxorubicin and cisplatin) chematheraty for advanced transitional cell carcinoma of the urinary tract. During July 1987 to June 1993, sixty eight patients with histologically proven advanced transitional cell carcinoma were treated with M-VAC chemotherapy at Seoul National University HospitaL Amang them, 43 patients with index lesions who received more than 2 cycles of chemotherapy, and were adequately followed up were analyzed for M-VAC chematherapy. Thirty nine patients were men and 4 women with the median age of 59 years. They were followed for 9 to 61 months with the median of 27 months after completion of chemotherapy. Of 43 eligible patients, complete remission was found in 9 patients(20.9%) and partial remis- sion in 1 l(25.6%), showing 46.5% of overa11 response rate. The overall median survival of the 43 patients were 14 months. In 9 patients with complete remission, the median duration of remis- sion was more than 20 months and median survival was more than 25 months with the two year survival rate of 100%. In 11 patients with partial remission, the median duration of remission was 11 months and median survival was 19 months with the one year survial rate of 81.8% and two year survival rate of 30%. The median survial of the 23 nonresponders was 10 months, with one and two year survival rate of 39.1% and 4.8%. Of the l4 patients with lymph node metastasis without any distant metastasis, 7 patients(50%) showed complete remission and another 3 patients(21.4%) showed partial remission, with the overall response rate of 72.4%. In con- trary, of the 29 patients with distant metastasis with or without nodal metastasis, the overall response rate was 34.5% including complete remission of only in 2 patients(6.9%). Toxicity was not negligible. Myelosuppression was observed in 58.1% of the patients, sepsis in 11.6/, renal toxicity in 48.8% and mucositis in 39.5%, but chemotherpy related death was not observed. M-VAC chemotherapy is apparently beneficial in patients with advanced transitional cell carcinoma of the urinary tract, especially with nodal metastasis, despite significant toxicity.

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