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

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 the...

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Autores principales: Li, Yanze, Xu, Kai, Zhang, Ye, Mao, Hu, Qiu, Qiangmin, Yan, Zhiwei, Liu, Xiuheng, Du, Yang, Chen, Zhiyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591420/
https://www.ncbi.nlm.nih.gov/pubmed/37872487
http://dx.doi.org/10.1186/s12885-023-11340-0
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author Li, Yanze
Xu, Kai
Zhang, Ye
Mao, Hu
Qiu, Qiangmin
Yan, Zhiwei
Liu, Xiuheng
Du, Yang
Chen, Zhiyuan
author_facet Li, Yanze
Xu, Kai
Zhang, Ye
Mao, Hu
Qiu, Qiangmin
Yan, Zhiwei
Liu, Xiuheng
Du, Yang
Chen, Zhiyuan
author_sort Li, Yanze
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11340-0.
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spelling pubmed-105914202023-10-24 Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro Li, Yanze Xu, Kai Zhang, Ye Mao, Hu Qiu, Qiangmin Yan, Zhiwei Liu, Xiuheng Du, Yang Chen, Zhiyuan BMC Cancer Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11340-0. BioMed Central 2023-10-23 /pmc/articles/PMC10591420/ /pubmed/37872487 http://dx.doi.org/10.1186/s12885-023-11340-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Yanze
Xu, Kai
Zhang, Ye
Mao, Hu
Qiu, Qiangmin
Yan, Zhiwei
Liu, Xiuheng
Du, Yang
Chen, Zhiyuan
Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro
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 Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591420/
https://www.ncbi.nlm.nih.gov/pubmed/37872487
http://dx.doi.org/10.1186/s12885-023-11340-0
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