Cancer Research and Treatment

Original Articles

Genitourinary cancer

Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy: Bokyung Ahn, Doeun Kim, Kye Jin Park, Ja-Min Park, Sun Young Yoon, Bumsik Hong, Yong Mee Cho, Deokhoon Kim; Cancer Res Treat. 2024;56(3):856-870. Published online December 18, 2023; DOI: https://doi.org/10.4143/crt.2023.1150

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Purpose
In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively.
Materials and Methods
Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data.
Results
Patients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001).
Conclusion
According to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

Citations

Citations to this article as recorded by

Papillary renal neoplasm with reverse polarity shows benign behavior: Results from a 77-case clinicopathological and molecular study
Yong Il Lee, Ja-Min Park, Sun Young Yoon, Cheryn Song, Yong Mee Cho
Annals of Diagnostic Pathology.2026; 80: 152498. CrossRef
Diagnostic accuracy of upper tract urothelial carcinoma using biopsy, urinary cytology, and nephroureterectomy specimens: A tertiary cancer center experience
Jianping Zhao, Yuan Shen, Ming Guo, Surena F Matin, Donna E Hansel, Charles C Guo
American Journal of Clinical Pathology.2024;[Epub] CrossRef
Clinical Significance of Tumor Location for Ureteroscopic Tumor Grading in Upper Tract Urothelial Carcinoma
Satoshi Katayama, Benjamin Pradere, Nico C. Grossman, Aaron M. Potretzke, Stephen A. Boorjian, Alireza Ghoreifi, Siamak Daneshmand, Hooman Djaladat, John P. Sfakianos, Andrea Mari, Zine-Eddine Khene, David D’andrea, Nozomi Hayakawa, Kazutoshi Fujita, Axel
Journal of Endourology.2024; 38(11): 1156. CrossRef
Development and validation of a radiomics-based nomogram for predicting pathological grade of upper urinary tract urothelial carcinoma
Yanghuang Zheng, Hongjin Shi, Shi Fu, Haifeng Wang, Xin Li, Zhi Li, Bing Hai, Jinsong Zhang
BMC Cancer.2024;[Epub] CrossRef

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Genomic Sequencing for Bladder Urothelial Carcinoma and Its Clinical Implications for Immunotherapy: Ryul Kim, Jung Yong Hong, Jeeyun Lee, Ghee Young Kwon, Byong Chang Jeong, Se Hoon Park; Cancer Res Treat. 2022;54(3):894-906. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.854

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to explore the genomic and transcriptomic landscape of bladder cancer (BC) and its implication for treatment with an immune checkpoint inhibitor (ICI).
Materials and Methods
We analyzed whole-exome and -transcriptome sequences of tumor samples from 64 BC patients who underwent surgical resection with either transurethral resection or radical cystectomy. For exploratory purposes, programmed death-ligand 1 (PD-L1) expression was evaluated in a subset of patients (n=57) including those treated with ICI (n=8).
Results
We identified frequent molecular dysregulations in chromatin regulatory genes (KDM6A, ARID1A, MLL2, and STAG2) and recurrent copy number alterations. Thirty-five samples (54.7%) were PD-L1–positive (PD-L1 combined positive score ≥ 1) with a significantly higher exonic tumor mutational burden (TMB) compared to PD-L1–negative BC samples (p=0.010). We observed that various immune-responsive pathways, including the PD-L1 signaling pathway, were enriched significantly in PD-L1–positive BCs. Interestingly, genes in the CTLA4 pathway were enriched significantly in PD-L1–positive BC as well. Among eight patients who received ICI, progressive disease was confirmed in one patient, whose tumor had low exonic TMB, negative PD-L1 status, and a relatively colder microenvironment.
Conclusion
Gaining new insights into the molecular landscape of BC will improve treatment strategies. Our analysis suggests a rationale for studying dual checkpoint inhibition against BC.

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Immune checkpoint inhibitors in bladder cancer: from mechanistic insights to emerging combination frontlines
Mohammad Mahdi Ajalli, Yalda Sansebli, Davood Ekrami, Fatemeh Alaeenejad, Ainaz Abbasi, Pooya Eini, Farnaz Hassanzadeh, Nastaran Bahrami
Clinical and Experimental Medicine.2026;[Epub] CrossRef
Perspective on the integration of radiomics and spatial omics in the analysis of the tumor microenvironment of bladder cancer and prospects for precision diagnosis and treatment
Yan Dong, Yunwei Su
Frontiers in Immunology.2026;[Epub] CrossRef
Targeting the PD-1/PD-L1 Signaling Pathway for Cancer Therapy: Focus on Biomarkers
Areti Strati, Christos Adamopoulos, Ioannis Kotsantis, Amanda Psyrri, Evi Lianidou, Athanasios G. Papavassiliou
International Journal of Molecular Sciences.2025; 26(3): 1235. CrossRef
Development of a Technique for Diagnosis and Screening of Superficial Bladder Cancer by Cell-Pellet DNA From Urine Sample
Jaekwon Seok, Hee Jeong Kwak, Chan-Koo Kang, Ah Ram Kim, Woo Suk Choi, Hyoung Keun Park, Sung Hyun Paick, Hyeong Gon Kim, Yeonjoo Kwak, Tak-Il Jeon, Kyung Min Lim, Baeckseung Lee, Aram Kim, Ssang-Goo Cho
Laboratory Investigation.2025; 105(6): 104124. CrossRef
Sex-Specific Associations of Glycemic Status and Smoking with Bladder Cancer Risk: A Nationwide Cohort Study
Joo-Hyun Park, Jung Yong Hong, Kyungdo Han, Jay J. Shen
Cancers.2025; 17(13): 2262. CrossRef
The role of lysine-specific demethylase 6A (KDM6A) in tumorigenesis and its therapeutic potentials in cancer therapy
Li-Juan Chen, Xin-Yang Xu, Xiao-Dan Zhong, Yan-Jun Liu, Ming-Hui Zhu, Fan Tao, Chang-Yun Li, Qiu-Sheng She, Guan-Jun Yang, Jiong Chen
Bioorganic Chemistry.2023; 133: 106409. CrossRef
A novel cuproptosis-related lncRNAs signature predicts prognostic and immune of bladder urothelial carcinoma
Zheng Zhou, Yusong Zhou, Wei Liu, Jing Dai
Frontiers in Genetics.2023;[Epub] CrossRef
Implication of KDM6A in Bladder Cancer
Marianne Matar, Gilles Prince, Ibrahim Hamati, Maria Baalbaky, Jonas Fares, Marc Aoude, Charbel Matar, Hampig Raphael Kourie
Pharmacogenomics.2023; 24(9): 509. CrossRef
Subsequent Systemic Therapy following Platinum and Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma
Joohyun Hong, Hyun Hwan Sung, Byong Chang Jeong, Se Hoon Park
Biomedicines.2022; 10(8): 2005. CrossRef
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Cuproptosis-related lncRNA signatures predict prognosis and immune relevance of kidney renal papillary cell carcinoma
Tongjin Xie, Bin Liu, Dongbo Liu, Yusong Zhou, Qingping Yang, Dai Wang, Mengjie Tang, Wei Liu
Frontiers in Pharmacology.2022;[Epub] CrossRef

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260 Download
10 Web of Science
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Prognostic Value of TP53 Mutation for Transcatheter Arterial Chemoembolization Failure/Refractoriness in HBV-Related Advanced Hepatocellular Carcinoma: Miao Xue, Yanqin Wu, Wenzhe Fan, Jian Guo, Jialiang Wei, Hongyu Wang, Jizhou Tan, Yu Wang, Wang Yao, Yue Zhao, Jiaping Li; Cancer Res Treat. 2020;52(3):925-937. Published online March 30, 2020; DOI: https://doi.org/10.4143/crt.2019.533

Abstract PDF PubReader ePub

Purpose
This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE).
Materials and Methods
From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA).
Results
Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness.
Conclusion
Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

Citations

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Concurrent Biopsy During Liver-Directed Therapy: Considerations, Techniques, and Expanding Role in Clinical Practice
Daniel M. DePietro, Ryan M. Kiefer, Kelley Weinfurtner, Matthew L. Hung
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Advances in understanding the roles of TP53 mutations in pancreatic and hepatobiliary cancers
James A. McCubrey, Matilde Y. Follo, Stefano Ratti, Lucia Manzoli, Lucio Cocco, Melchiorre Cervello, Giuseppa Augello
Advances in Biological Regulation.2026; 101: 101169. CrossRef
Construction of ATOX1 targeted nano gel based on cuproptosis mechanism and its role in reversing TACE refractoriness of hepatocellular carcinoma
Chao Chen, Songlin Song, Wenlong Wu, Ningjun Yu, Chuansheng Zheng, Guofeng Zhou, Yanqiao Ren, Xiangjun Dong
Journal of Nanobiotechnology.2026;[Epub] CrossRef
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Qi Fan, Pengcheng Wei, Delin Ma, Qian Cheng, Jie Gao, Jiye Zhu, Zhao Li
Surgery Open Science.2025; 23: 16. CrossRef
TP53 Mutation Predicts Worse Survival and Earlier Local Progression in Patients with Hepatocellular Carcinoma Treated with Transarterial Embolization
Ken Zhao, Anita Karimi, Luke Kelly, Elena Petre, Brett Marinelli, Erica S. Alexander, Vlasios S. Sotirchos, Joseph P. Erinjeri, Anne Covey, Constantinos T. Sofocleous, James J. Harding, William Jarnagin, Carlie Sigel, Efsevia Vakiani, Etay Ziv, Hooman Yar
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Wanqing Shen, Zhi Li, Jinyi Huang, Guixiong Zhang, Yiyang Tang, Wenzhe Fan, Jiaping Li
Translational Oncology.2025; 58: 102437. CrossRef
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Ken Zhao, Harrison Blume, Elena N. Petre, Dimitrios Xenos, Zuzanna Kobus, Erica S. Alexander, Vlasios S. Sotirchos, Ruben Geevarghese, Anne Covey, Joseph P. Erinjeri, Etay Ziv, Constantinos T. Sofocleous, James J. Harding, Kevin Soares, Carlie Sigel, Efse
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Efficacy and safety analysis of D-TACE combined with lenvatinib in the treatment of hepatocellular carcinoma refractory to C-TACE
Haohao Lu, Bin Liang, Chuansheng Zheng, Xiangwen Xia
BMC Gastroenterology.2025;[Epub] CrossRef
Clinical Therapy: HAIC Combined with Tyrosine Kinase Inhibitors and Programmed Cell Death Protein-1 Inhibitors versus HAIC Alone for Unresectable Hepatocellular Carcinoma
Baokun Liu, Lujun Shen, Wen Liu, Zhiyong Zhang, Jieqiong Lei, Zhengguo Li, Qinquan Tan, Hengfei Huang, Xingdong Wang, Weijun Fan
Journal of Hepatocellular Carcinoma.2024; Volume 11: 1557. CrossRef
Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE
Libo Wang, Jiahui Cao, Zaoqu Liu, Shitao Wu, Yin Liu, Ruopeng Liang, Rongtao Zhu, Weijie Wang, Jian Li, Yuling Sun
Hepatology Communications.2024;[Epub] CrossRef
Development and validation of survival prediction models for patients with hepatocellular carcinoma treated with transcatheter arterial chemoembolization plus tyrosine kinase inhibitors
Kun Huang, Haikuan Liu, Yanqin Wu, Wenzhe Fan, Yue Zhao, Miao Xue, Yiyang Tang, Shi-Ting Feng, Jiaping Li
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Identification of BRD7 by whole-exome sequencing as a predictor for intermediate-stage hepatocellular carcinoma in patients undergoing TACE
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Guixiong Zhang, Wenzhe Fan, Hongyu Wang, Jie Wen, Jizhou Tan, Miao Xue, Jiaping Li
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
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