Cancer research and treatment · 2026
Integrative Genomic Analysis Reveals Molecular and Clinical Disparities between Bladder and Upper Tract Urothelial Carcinoma in K-MASTER Program.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Kim Jiwon, Kim Jwa Hoon, Park Kyong Hwa, Kang Seok Ho, Lee Jae Lyun, Bae Woo Kyun, Kim Miso, Choi Jong Gwon, Park Inkeun, Park Ji Hyun, Shin Sang Joon, Jo Jungmin, Park Se Hoon, Park Kwonoh, Lee Ji Yoon, Song Youjin, Lee Dayoung, Moon Namsung, Sa Jason K, Choi Yoon Ji
Аннотация
PURPOSE: The clinical outcome of urothelial carcinoma presents significant variability, reflecting its molecular composition, epidemiologic attributes, and primary site of origin. Despite histological similarities, upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BLCA) represent two distinct disease entities with disparate treatment responses and mutational patterns.
MATERIALS AND METHODS: To assess the impact of molecular heterogeneity on treatment outcomes, we conducted a comprehensive genomic analysis of 231 metastatic urothelial carcinoma patients, including 175 patients with BLCA and 56 patients with UTUC, in the K-MASTER program.
RESULTS: Our investigation unveiled dynamic molecular properties and mutational patterns in key molecules, including TP53, FGFR3, CREBBP, and SPEN. BLCA patients demonstrated enrichment of APOBEC mutational signature activities, whereas UTUC patients were characterized by activation of the cell cycle pathway. Transcriptome analysis uncovered unique biological signatures, highlighting increased cell migration and WNT signaling in BLCA, while FGFR3 and stem-cell-like pathways predominated in UTUC. Moreover, our study highlighted increased resistance to platinum-based chemotherapy and immunotherapy among UTUC patients. Importantly, tumor mutational burden (TMB) emerged as a robust independent predictor of immunotherapy response in BLCA. Additionally, a machine learning-based multivariable model identified FGFR3 mutation as a molecular determinant associated with favorable clinical outcomes, in contrast to FGFR2 mutations, which were linked to increased resistance to chemotherapy. The study also has limitations, including a limited sample size of UTUC patients and a lack of functional validation of the identified molecular mechanism.
CONCLUSION: Our findings provide unprecedented insights into the significance of molecular and clinical disparities in urothelial carcinoma, facilitating disease-specific treatment interventions.
MATERIALS AND METHODS: To assess the impact of molecular heterogeneity on treatment outcomes, we conducted a comprehensive genomic analysis of 231 metastatic urothelial carcinoma patients, including 175 patients with BLCA and 56 patients with UTUC, in the K-MASTER program.
RESULTS: Our investigation unveiled dynamic molecular properties and mutational patterns in key molecules, including TP53, FGFR3, CREBBP, and SPEN. BLCA patients demonstrated enrichment of APOBEC mutational signature activities, whereas UTUC patients were characterized by activation of the cell cycle pathway. Transcriptome analysis uncovered unique biological signatures, highlighting increased cell migration and WNT signaling in BLCA, while FGFR3 and stem-cell-like pathways predominated in UTUC. Moreover, our study highlighted increased resistance to platinum-based chemotherapy and immunotherapy among UTUC patients. Importantly, tumor mutational burden (TMB) emerged as a robust independent predictor of immunotherapy response in BLCA. Additionally, a machine learning-based multivariable model identified FGFR3 mutation as a molecular determinant associated with favorable clinical outcomes, in contrast to FGFR2 mutations, which were linked to increased resistance to chemotherapy. The study also has limitations, including a limited sample size of UTUC patients and a lack of functional validation of the identified molecular mechanism.
CONCLUSION: Our findings provide unprecedented insights into the significance of molecular and clinical disparities in urothelial carcinoma, facilitating disease-specific treatment interventions.