Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Basement membrane; Bladder cancer; Immune; LAMA2; Signature.