Background: Despite clinical and pathological risk tools, predicting outcomes in non-muscle-invasive bladder cancer (NMIBC), particularly high-grade (HG) cases, remains challenging due to its unpredictable recurrence and progression. There is an urgent need for molecular biomarkers to enhance risk stratification and guide treatment. Methods: We assessed the prognostic potential of eight miRNAs (miR-9, miR-143, miR-182, miR-205, miR-27a, miR-369, let-7c, and let-7g) in a cohort of ninety patients with primary bladder cancer. Expression data were retrieved from our previously published studies. Kaplan–Meier’s and Cox’s regression analyses were used to evaluate the associations with overall survival (OS), metastasis-free survival (MFS), and clinical outcomes. Principal component analysis (PCA) was performed to identify informative miRNA combinations. Target gene prediction, pathway enrichment (DAVID), and drug–gene interaction mapping (DGIdb) were conducted in silico. Results: A high expression of let-7g and miR-9 was significantly associated with better OS in HG NMIBC and MIBC, respectively (p= 0.013 andp= 0.000). MiR-9 downregulation correlated with metastasis in MIBC (p= 0.018). Among all combinations, miR-205 and miR-27a best predicted intermediate-risk NMIBC progression and recurrence (r2= 0.982,p= 0.000). A functional analysis revealed that these miRNAs regulate key cancer-related pathways (MAPK, mTOR, and p53) through genes such as TP53, PTEN, and CDKN1A. Drug interaction mapping identified nine target genes (e.g., DAPK1, ATR, and MTR) associated with eight FDA-approved bladder cancer therapies, including cisplatin and gemcitabine. Conclusions: Let-7g, miR-9, miR-143, miR-182, and miR-205 emerged as promising biomarkers for outcome prediction in NMIBC. Their integration into liquid biopsy platforms could support non-invasive monitoring and personalized treatment strategies. These findings warrant validation in larger, prospective studies and through functional assays.
背景：尽管存在临床和病理风险评估工具，但由于非肌层浸润性膀胱癌（NMIBC）尤其是高级别（HG）病例的复发和进展难以预测，其预后判断仍具挑战。亟需分子生物标志物以优化风险分层并指导治疗。方法：我们在90例原发性膀胱癌患者队列中评估了八种miRNA（miR-9、miR-143、miR-182、miR-205、miR-27a、miR-369、let-7c和let-7g）的预后潜力。表达数据来源于我们既往发表的研究。采用Kaplan-Meier法和Cox回归分析评估其与总生存期（OS）、无转移生存期（MFS）及临床结局的关联性。通过主成分分析（PCA）筛选具有预测价值的miRNA组合。通过生物信息学方法进行靶基因预测、通路富集分析（DAVID）及药物-基因相互作用图谱构建（DGIdb）。结果：let-7g高表达与HG NMIBC患者更好的OS显著相关（p=0.013），而miR-9高表达与肌层浸润性膀胱癌（MIBC）患者更好的OS显著相关（p=0.000）。miR-9下调与MIBC转移相关（p=0.018）。在所有组合中，miR-205与miR-27a对中危NMIBC进展和复发的预测效能最佳（r²=0.982，p=0.000）。功能分析显示这些miRNA通过TP53、PTEN、CDKN1A等基因调控关键癌症相关通路（MAPK、mTOR和p53）。药物相互作用图谱分析发现九个靶基因（如DAPK1、ATR和MTR）与八种FDA批准的膀胱癌疗法（包括顺铂和吉西他滨）存在关联。结论：let-7g、miR-9、miR-143、miR-182和miR-205可作为NMIBC预后预测的潜在生物标志物。将其整合至液体活检平台有助于实现无创监测和个体化治疗策略。这些发现需要在更大规模的前瞻性研究及功能实验中进行验证。
肿瘤(癌症)患者之家