Kim Mingyu, Jung Euihyun, Song Geehyun, Joung Jaeyoung, Chung Jinsoo, Seo Hokyung, Lee Hyungho
Center for Urologic Cancer, National Cancer Center, 323, Ilsan-Ro, Ilsandong-Gu, Goyang-Si 10408, Gyeonggi-Do, Republic of Korea.
Int J Mol Sci. 2025 Apr 22;26(9):3959. doi: 10.3390/ijms26093959.
Bladder cancer, especially muscle-invasive bladder cancer (MIBC), poses significant treatment challenges due to its aggressive nature and poor prognosis, often necessitating cisplatin-based chemotherapy. While cisplatin effectively reduces tumor burden, its nephrotoxic effects, specifically cisplatin-induced acute kidney injury (AKI), limit its clinical use. This study investigates as a potential biomarker for bladder cancer progression and AKI. Plasma and urine levels were measured in bladder cancer patients undergoing cisplatin treatment, showing elevated baseline levels compared to controls, suggesting a link with bladder cancer pathology rather than cisplatin-induced AKI. Functional network and Gene Ontology (GO) enrichment analyses identified 's interactions with NADPH oxidase pathways, particularly family genes, and highlighted its roles in cell adhesion, migration, and cytoskeletal organization-processes critical for tumor invasiveness. Notably, and expression were significantly higher in MIBC than in non-muscle-invasive bladder cancer (NMIBC), with a strong correlation between and (r = 0.62) in MIBC, suggesting a subtype-specific interaction. Kaplan-Meier survival analysis using The Cancer Genome Atlas bladder cancer (TCGA-BLCA) data further demonstrated that low expression is significantly associated with poor overall and disease-specific survival in MIBC patients, reinforcing its role as a prognostic biomarker. In conclusion, is a promising biomarker for identifying the invasive characteristics of MIBC and predicting patient outcomes. These findings underscore the importance of pathways in MIBC and suggest the need for further research into targeted biomarkers for bladder cancer progression and cisplatin-induced AKI to improve patient outcomes in high-risk cases.
膀胱癌,尤其是肌层浸润性膀胱癌(MIBC),因其侵袭性强和预后差而带来重大治疗挑战,常常需要基于顺铂的化疗。虽然顺铂能有效减轻肿瘤负担,但其肾毒性作用,特别是顺铂诱导的急性肾损伤(AKI),限制了其临床应用。本研究调查了[具体物质名称未给出]作为膀胱癌进展和AKI的潜在生物标志物。对接受顺铂治疗的膀胱癌患者的血浆和尿液[具体物质名称未给出]水平进行了测量,结果显示与对照组相比基线水平升高,这表明其与膀胱癌病理相关,而非顺铂诱导的AKI。功能网络和基因本体(GO)富集分析确定了[具体物质名称未给出]与NADPH氧化酶途径的相互作用,特别是[具体家族基因未给出]家族基因,并突出了其在细胞黏附、迁移和细胞骨架组织中的作用,这些过程对肿瘤侵袭至关重要。值得注意的是,[具体物质名称未给出]和[另一具体物质名称未给出]的表达在MIBC中显著高于非肌层浸润性膀胱癌(NMIBC),在MIBC中[具体物质名称未给出]和[另一具体物质名称未给出]之间存在强相关性(r = 0.62),表明存在亚型特异性相互作用。使用癌症基因组图谱膀胱癌(TCGA - BLCA)数据进行的Kaplan - Meier生存分析进一步表明,低[具体物质名称未给出]表达与MIBC患者的总体和疾病特异性生存率差显著相关,强化了其作为预后生物标志物的作用。总之,[具体物质名称未给出]是用于识别MIBC侵袭特征和预测患者预后的有前景的生物标志物。这些发现强调了[具体物质名称未给出]途径在MIBC中的重要性,并表明需要进一步研究针对膀胱癌进展和顺铂诱导的AKI的靶向生物标志物,以改善高危病例的患者预后。