Jin Yi, Huang Siwei, Wang Zhanwang
Department of Radiation Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Key Laboratory of Translational Radiation Oncology, Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Front Oncol. 2023 Jul 13;13:1191398. doi: 10.3389/fonc.2023.1191398. eCollection 2023.
Muscle-invasive bladder cancer (MIBC) develops lymph node (LN) metastasis or distant metastasis, leading to recurrence and poor prognosis. The five-year survival rate of MIBC with LN or distant metastasis is only 8.1%; therefore, there is an urgent need to identify reliable biomarkers for prognosis and treatment regimen for patients with bladder cancer (BLCA).
SEER database was used to select important clinical characteristics for MIBC. Then, weighted gene co-expression network analysis (WGCNA) was employed to identify differentially expressed genes (DEGs) to recognize significant co-expression modules by calculating the correlation between the modules and clinical data. Furthermore, Cox regression and lasso analysis were applied to screen prognostic hub genes and establish the risk predictive model. Bladder cancer cell lines (UMUC3 and 5637) were used for experimental validation .
Cox analysis of 122,600 MIBC patients showed that the N stage was the most important clinical factor. A total of 4,597 DEGs were calculated between N0 and N+ patients, and WGCNA with these DEGs in 368 samples revealed that expression of turquoise was positively and strongly correlated with the N stage. Eight genes were identified as important prognostic candidates using lasso regression based on Cox analysis and STRING database. Combining GEO datasets, literature, and clinical factors, we identified and as novel prognostic biomarkers. CCK8 assay showed that depletion of or significantly inhibited the proliferation of BLCA cells, and flow cytometry indicated that knockdown of or induced the apoptosis of BLCA cells. Transwell assay also showed that silencing of or weakened the migration and invasiveness of BLCA cells.
We constructed a new eight-gene risk model to provide novel prognostic biomarkers and therapeutic targets for BLCA.
肌层浸润性膀胱癌（MIBC）会发生淋巴结（LN）转移或远处转移，导致复发且预后不良。发生LN转移或远处转移的MIBC患者的五年生存率仅为8.1%；因此，迫切需要为膀胱癌（BLCA）患者确定可靠的预后生物标志物和治疗方案。
利用SEER数据库选择MIBC的重要临床特征。然后，采用加权基因共表达网络分析（WGCNA）来识别差异表达基因（DEG），通过计算模块与临床数据之间的相关性来识别显著的共表达模块。此外，应用Cox回归和套索分析来筛选预后关键基因并建立风险预测模型。使用膀胱癌细胞系（UMUC3和5637）进行实验验证。
对122,600例MIBC患者的Cox分析表明，N分期是最重要的临床因素。在N0和N+患者之间共计算出4,597个DEG，对368个样本中的这些DEG进行WGCNA分析显示，绿松石色模块的表达与N分期呈正相关且相关性很强。基于Cox分析和STRING数据库，使用套索回归确定了8个基因作为重要的预后候选基因。结合GEO数据集、文献和临床因素，我们将[具体基因1]和[具体基因2]确定为新的预后生物标志物。CCK8检测表明，敲低[具体基因1]或[具体基因2]可显著抑制BLCA细胞的增殖，流式细胞术表明，敲低[具体基因1]或[具体基因2]可诱导BLCA细胞凋亡。Transwell检测还表明，沉默[具体基因1]或[具体基因2]会减弱BLCA细胞的迁移和侵袭能力。
我们构建了一个新的八基因风险模型，为BLCA提供了新的预后生物标志物和治疗靶点。
