Department of Urology, Renmin Hospital, Wuhan University, Wuhan, 430060, Hubei, China.
Institute of Urologic Disease, Renmin Hospital, Wuhan University, Wuhan, 430060, Hubei, China.
BMC Cancer. 2023 Oct 23;23(1):1021. doi: 10.1186/s12885-023-11340-0.
Bladder urothelial carcinoma (BLCA) is the most common genitourinary cancer and the prognosis of patients is often poor. However, studies of basement membrane-related genes (BM-related genes) in BLCA are less reported. Therefore, we established a BM-related genes signature to explore their functional and prognostic value in BLCA.
In this study, a BM-related genes signature was constructed by LASSO-Cox regression analysis, and then a series of bioinformatics methods was used to assess the accuracy and validity of the signature. We constructed a nomogram for clinical application and also screened for possible therapeutic drugs. To investigate the functions and pathways affected by BM-related genes in BLCA, we performed functional enrichment analyses. In addition, we analyzed the immune cell infiltration landscape and immune checkpoint-related genes in the high and low-risk groups. Finally, we confirmed the prognostic value of BM-related genes in BLCA in vitro.
Combining multiple bioinformatics approaches, we identified a seven-gene signature. The accuracy and validity of this signature in predicting BLCA patients were confirmed by the test cohort. In addition, the risk score was strongly correlated with prognosis, immune checkpoint genes, drug sensitivity, and immune cell infiltration landscape. The risk score is an independent prognostic factor for BLCA patients. Further experiments revealed that all seven signature genes were differentially expressed between BLCA cell lines and normal bladder cells. Finally, overexpression of LAMA2 inhibited the migration and invasion ability of BLCA cell lines.
In summary, the BM-related genes signature was able to predict the prognosis of BLCA patients accurately, indicating that the BM-related genes possess great clinical value in the diagnosis and treatment of BLCA. Moreover, LAMA2 could be a potential therapeutic target, which provides new insights into the application of the BM-related genes in BLCA patients.
膀胱癌（BLCA）是最常见的泌尿生殖系统癌症，患者的预后通常较差。然而，关于 BLCA 中基底膜相关基因（BM 相关基因）的研究报道较少。因此，我们建立了一个 BM 相关基因特征，以探讨其在 BLCA 中的功能和预后价值。
本研究通过 LASSO-Cox 回归分析构建了一个 BM 相关基因特征，然后采用一系列生物信息学方法评估特征的准确性和有效性。我们构建了一个列线图用于临床应用，并筛选了可能的治疗药物。为了研究 BM 相关基因在 BLCA 中影响的功能和途径，我们进行了功能富集分析。此外，我们分析了高低风险组中免疫细胞浸润的景观和免疫检查点相关基因。最后，我们在体外验证了 BM 相关基因在 BLCA 中的预后价值。
通过多种生物信息学方法的结合，我们确定了一个由七个基因组成的特征。该特征在预测 BLCA 患者中的准确性和有效性通过测试队列得到了验证。此外，风险评分与预后、免疫检查点基因、药物敏感性和免疫细胞浸润景观密切相关。风险评分是 BLCA 患者的独立预后因素。进一步的实验表明，所有七个特征基因在 BLCA 细胞系和正常膀胱细胞之间均有差异表达。最后，LAMA2 的过表达抑制了 BLCA 细胞系的迁移和侵袭能力。
总之，BM 相关基因特征能够准确预测 BLCA 患者的预后，表明 BM 相关基因在 BLCA 的诊断和治疗中具有重要的临床价值。此外，LAMA2 可能是一个潜在的治疗靶点，为 BM 相关基因在 BLCA 患者中的应用提供了新的思路。
