Tao Junyue, Li Xiao, Liang Chaozhao, Liu Yi, Zhou Jun
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China.
Institute of Urology, Anhui Medical University, Hefei, China.
Front Oncol. 2022 Oct 24;12:1026331. doi: 10.3389/fonc.2022.1026331. eCollection 2022.
Clear cell renal cell carcinoma (ccRCC) is a malignant tumor with limited treatment options. A recent study confirmed the involvement of basement membrane (BM) genes in the progression of many cancers. Therefore, we studied the role and prognostic significance of BM genes in ccRCC.
Co-expression analysis of ccRCC-related information deposited in The Cancer Genome Atlas database and a BM geneset from a recent study was conducted. The differentially expressed BM genes were validated using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Least absolute shrinkage and selection operator regression and univariate Cox regression analyses were performed to identify a BM gene signature with prognostic significance for ccRCC. Multivariate Cox regression, time-dependent receiver operating characteristic, Kaplan-Meier, and nomogram analyses were implemented to appraise the prognostic ability of the signature and the findings were further verified using a Gene Expression Omnibus dataset. Additionally, immune cell infiltration and and pathway enrichment analyses were performed using ImmuCellAI and Gene Set Enrichment Analysis (GSEA), respectively. Finally, the DSIGDB dataset was used to screen small-molecule therapeutic drugs that may be useful in treating ccRCC patients.
We identified 108 BM genes exhibiting different expression levels compared to that in normal kidney tissues, among which 32 genes had prognostic values. The qRT-PCR analyses confirmed that the expression patterns of four of the ten selected genes were the same as the predicted ones. Additionally, we successfully established and validated a ccRCC patient prediction model based on 16 BM genes and observed that the model function is an independent predictor. GSEA revealed that differentially expressed BM genes mainly displayed significant enrichment of tumor and metabolic signaling cascades. The BM gene signature was also associated with immune cell infiltration and checkpoints. Eight small-molecule drugs may have therapeutic effects on ccRCC patients.
This study explored the function of BM genes in ccRCC for the first time. Reliable prognostic biomarkers that affect the survival of ccRCC patients were determined, and a BM gene-based prognostic model was established.
透明细胞肾细胞癌（ccRCC）是一种治疗选择有限的恶性肿瘤。最近的一项研究证实了基底膜（BM）基因与许多癌症进展有关。因此，我们研究了BM基因在ccRCC中的作用及预后意义。
对癌症基因组图谱数据库中存储的ccRCC相关信息与近期一项研究中的BM基因集进行共表达分析。使用定量逆转录聚合酶链反应（qRT-PCR）验证差异表达的BM基因。进行最小绝对收缩和选择算子回归以及单变量Cox回归分析，以确定对ccRCC具有预后意义的BM基因特征。实施多变量Cox回归、时间依赖性受试者工作特征、Kaplan-Meier和列线图分析，以评估该特征的预后能力，并使用基因表达综合数据库数据集进一步验证结果。此外，分别使用ImmuCellAI和基因集富集分析（GSEA）进行免疫细胞浸润和通路富集分析。最后，使用DSIGDB数据集筛选可能对治疗ccRCC患者有用的小分子治疗药物。
我们鉴定出108个与正常肾组织相比表达水平不同的BM基因，其中32个基因具有预后价值。qRT-PCR分析证实，所选的10个基因中有4个的表达模式与预测的相同。此外，我们成功建立并验证了一个基于16个BM基因的ccRCC患者预测模型，并观察到该模型功能是一个独立预测因子。GSEA显示，差异表达的BM基因主要在肿瘤和代谢信号级联中显著富集。BM基因特征也与免疫细胞浸润和检查点相关。8种小分子药物可能对ccRCC患者有治疗作用。
本研究首次探索了BM基因在ccRCC中的功能。确定了影响ccRCC患者生存的可靠预后生物标志物，并建立了基于BM基因的预后模型。
