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 exp...

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Main Authors: Yanze Li, Kai Xu, Ye Zhang, Hu Mao, Qiangmin Qiu, Zhiwei Yan, Xiuheng Liu, Yang Du, Zhiyuan Chen
Format: Article
Language:English
Published: BMC 2023-10-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-023-11340-0
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author Yanze Li
Kai Xu
Ye Zhang
Hu Mao
Qiangmin Qiu
Zhiwei Yan
Xiuheng Liu
Yang Du
Zhiyuan Chen
author_facet Yanze Li
Kai Xu
Ye Zhang
Hu Mao
Qiangmin Qiu
Zhiwei Yan
Xiuheng Liu
Yang Du
Zhiyuan Chen
author_sort Yanze Li
collection DOAJ
description 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.
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spelling doaj.art-5609df84de7f4ddd88bd6a52004801972023-11-26T13:36:32ZengBMCBMC Cancer1471-24072023-10-0123111510.1186/s12885-023-11340-0Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitroYanze Li0Kai Xu1Ye Zhang2Hu Mao3Qiangmin Qiu4Zhiwei Yan5Xiuheng Liu6Yang Du7Zhiyuan Chen8Department of Urology, Renmin Hospital, Wuhan UniversityDepartment of Urology, Renmin Hospital, Wuhan UniversityDepartment of Urology, Renmin Hospital, Wuhan UniversityDepartment of Urology, Renmin Hospital, Wuhan UniversityDepartment of Urology, Renmin Hospital, Wuhan UniversityDepartment of Urology, Renmin Hospital, Wuhan UniversityDepartment of Urology, Renmin Hospital, Wuhan UniversityDepartment of Urology, Renmin Hospital, Wuhan UniversityDepartment of Urology, Renmin Hospital, Wuhan UniversityAbstract 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.https://doi.org/10.1186/s12885-023-11340-0Basement membraneBladder cancerImmuneSignatureLAMA2
spellingShingle Yanze Li
Kai Xu
Ye Zhang
Hu Mao
Qiangmin Qiu
Zhiwei Yan
Xiuheng Liu
Yang Du
Zhiyuan Chen
Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro
BMC Cancer
Basement membrane
Bladder cancer
Immune
Signature
LAMA2
title Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro
title_full Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro
title_fullStr Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro
title_full_unstemmed Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro
title_short Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro
title_sort identification of a basement membrane related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro
topic Basement membrane
Bladder cancer
Immune
Signature
LAMA2
url https://doi.org/10.1186/s12885-023-11340-0
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