Zhang Chen, Yin Hubin, Li Tinghao, Chen Junrui, He Weiyang, Ren Ke, Li Bo, Liu Xudong
Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, China.
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Ann Med. 2025 Dec;57(1):2458211. doi: 10.1080/07853890.2025.2458211. Epub 2025 Jan 28.
Despite surgical and intravesical chemotherapy interventions, non-muscle invasive bladder cancer (NMIBC) poses a high risk of recurrence, which significantly impacts patient survival. Traditional clinical characteristics alone are inadequate for accurately assessing the risk of NMIBC recurrence, necessitating the development of novel predictive tools.
We analyzed microarray data of NMIBC samples obtained from the ArrayExpress and GEO databases. LASSO regression was utilized to develop the predictive signature. We combined gene signature and clinicopathological factors to construct a clinical nomogram for estimating NMIBC recurrence in a local cohort. Finally. the biological functions and potential mechanisms of SDCBP in bladder cancer were investigated experimentally and .
An 8-gene signature was developed, and its efficiency for predicting NMIBC recurrence was evaluated using Kaplan-Meier and time-dependent ROC curves in both training and validation datasets. Immunohistochemical testing revealed elevated levels of ACTN4 and SDCBP in recurrent NMIBC tissues. We integrated the two proteins with clinical factors to develop a nomogram model, which showed superior accuracy compared to individual parameters. Gene Set Variation Analysis and Gene Set Enrichment Analysis unveiled SDCBP exerted cancer-promoting biological processes, such as angiogenesis, EMT, metastasis and proliferation. Experimental procedures demonstrated that silencing SDCBP attenuated cell growth, glucose metabolism and extracellular acidification rate, accompanied by decreased expression of p-AKT, p-ERK1/2, LDHA and Vimentin.
The established 8-gene signature holds promise as a tool for predicting NMIBC recurrence, while targeting SDCBP may represent a potential strategy for delaying disease relapse.
尽管有手术和膀胱内化疗干预，但非肌层浸润性膀胱癌（NMIBC）仍具有较高的复发风险，这对患者的生存有显著影响。仅依靠传统临床特征不足以准确评估NMIBC复发风险，因此需要开发新的预测工具。
我们分析了从ArrayExpress和GEO数据库获得的NMIBC样本的微阵列数据。利用LASSO回归开发预测特征。我们将基因特征与临床病理因素相结合，构建了一个临床列线图，用于估计本地队列中NMIBC的复发情况。最后，通过实验研究了SDCBP在膀胱癌中的生物学功能和潜在机制。
开发了一个8基因特征，并在训练和验证数据集中使用Kaplan-Meier曲线和时间依赖性ROC曲线评估其预测NMIBC复发的效率。免疫组织化学检测显示，复发性NMIBC组织中ACTN4和SDCBP水平升高。我们将这两种蛋白质与临床因素整合，开发了一个列线图模型，该模型显示出比单个参数更高的准确性。基因集变异分析和基因集富集分析表明，SDCBP发挥促进癌症的生物学过程，如血管生成、上皮-间质转化、转移和增殖。实验过程表明，沉默SDCBP可减弱细胞生长、葡萄糖代谢和细胞外酸化率，同时p-AKT、p-ERK1/2、LDHA和波形蛋白的表达降低。
所建立的8基因特征有望成为预测NMIBC复发的工具，而靶向SDCBP可能是延缓疾病复发的潜在策略。
