Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer

Abstract Background Bladder cancer (BC) is one of the most common malignant diseases and the most common causes of cancer death worldwide. Immunotherapy has opened new avenues for precision treatment of bladder tumours, and immune checkpoint inhibitors (ICIs) have revolutionized the clinical treatme...

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Main Authors: Pengyu Hui, Feng Ni, Liang Zheng, Lei Jia, Zhe Wang
Format: Article
Language:English
Published: BMC 2023-04-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-023-10828-z
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author Pengyu Hui
Feng Ni
Liang Zheng
Lei Jia
Zhe Wang
author_facet Pengyu Hui
Feng Ni
Liang Zheng
Lei Jia
Zhe Wang
author_sort Pengyu Hui
collection DOAJ
description Abstract Background Bladder cancer (BC) is one of the most common malignant diseases and the most common causes of cancer death worldwide. Immunotherapy has opened new avenues for precision treatment of bladder tumours, and immune checkpoint inhibitors (ICIs) have revolutionized the clinical treatment strategy of bladder tumours. In addition, long non-coding RNA (lncRNA) plays an important role in regulating tumour development and immunotherapy efficacy. Methods We obtained genes with significant differences between anti-PD-L1 response and non-response from the Imvogor210 data set and combined with the bladder cancer expression data in the TCGA cohort to obtain immunotherapy-related lncRNA. Based on these lncRNAs, the prognostic risk model of bladder cancer was constructed and verified by GEO external data set. The characterization of immune cell infiltration and immunotherapy effects between high-risk and low-risk groups were then analysed. We predicted the ceRNA network and performed molecular docking of key target proteins. The functional experiments verified the function of SBF2-AS1. Results Three immunotherapy-related lncRNAs were identified as independent prognostic biomarkers for bladder cancer and a prognostic model of immunotherapy-related prognosis was constructed. Prognosis, immune cell infiltration, and immunotherapy efficacy were significantly different between high- and low-risk groups based on risk scores. Additionally, we established a ceRNA network of lncRNA(SBF2-AS1)-miRNA(has-miR-582-5p)-mRNA (HNRNPA2B1). Targeting the protein HNRNPA2B1 identified the top eight small molecule drugs with the highest affinity. Conclusion We developed a prognostic risk score model based on immune-therapy-related lncRNA, which was subsequently determined to be significantly associated with immune cell infiltration and immunotherapy response. This study not only helps to promote our understanding of immunotherapy-related lncRNA in the prognosis of BC, but also provides new ideas for clinical immunotherapy and the development of novel therapeutic drugs for patients.
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spelling doaj.art-44c0479f82b4487f92905bd4ffa54e672023-04-23T11:20:14ZengBMCBMC Cancer1471-24072023-04-0123111510.1186/s12885-023-10828-zIdentification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancerPengyu Hui0Feng Ni1Liang Zheng2Lei Jia3Zhe Wang4Department of Urology, The Second Affiliated Hospital of Xi’an Medical UniversityDepartment of Urology, The Second Affiliated Hospital of Xi’an Medical UniversityDepartment of Urology, The Second Affiliated Hospital of Xi’an Medical UniversityDepartment of Urology, The Second Affiliated Hospital of Xi’an Medical UniversityDepartment of Urology, Cancer Hospital of China Medical UniversityAbstract Background Bladder cancer (BC) is one of the most common malignant diseases and the most common causes of cancer death worldwide. Immunotherapy has opened new avenues for precision treatment of bladder tumours, and immune checkpoint inhibitors (ICIs) have revolutionized the clinical treatment strategy of bladder tumours. In addition, long non-coding RNA (lncRNA) plays an important role in regulating tumour development and immunotherapy efficacy. Methods We obtained genes with significant differences between anti-PD-L1 response and non-response from the Imvogor210 data set and combined with the bladder cancer expression data in the TCGA cohort to obtain immunotherapy-related lncRNA. Based on these lncRNAs, the prognostic risk model of bladder cancer was constructed and verified by GEO external data set. The characterization of immune cell infiltration and immunotherapy effects between high-risk and low-risk groups were then analysed. We predicted the ceRNA network and performed molecular docking of key target proteins. The functional experiments verified the function of SBF2-AS1. Results Three immunotherapy-related lncRNAs were identified as independent prognostic biomarkers for bladder cancer and a prognostic model of immunotherapy-related prognosis was constructed. Prognosis, immune cell infiltration, and immunotherapy efficacy were significantly different between high- and low-risk groups based on risk scores. Additionally, we established a ceRNA network of lncRNA(SBF2-AS1)-miRNA(has-miR-582-5p)-mRNA (HNRNPA2B1). Targeting the protein HNRNPA2B1 identified the top eight small molecule drugs with the highest affinity. Conclusion We developed a prognostic risk score model based on immune-therapy-related lncRNA, which was subsequently determined to be significantly associated with immune cell infiltration and immunotherapy response. This study not only helps to promote our understanding of immunotherapy-related lncRNA in the prognosis of BC, but also provides new ideas for clinical immunotherapy and the development of novel therapeutic drugs for patients.https://doi.org/10.1186/s12885-023-10828-zBladder cancerImmunotherapyLong non-coding RNAPrognosticceRNA networkMolecular docking
spellingShingle Pengyu Hui
Feng Ni
Liang Zheng
Lei Jia
Zhe Wang
Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer
BMC Cancer
Bladder cancer
Immunotherapy
Long non-coding RNA
Prognostic
ceRNA network
Molecular docking
title Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer
title_full Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer
title_fullStr Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer
title_full_unstemmed Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer
title_short Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer
title_sort identification of immunotherapy related lncrna signature for predicting prognosis immunotherapy responses and drug candidates in bladder cancer
topic Bladder cancer
Immunotherapy
Long non-coding RNA
Prognostic
ceRNA network
Molecular docking
url https://doi.org/10.1186/s12885-023-10828-z
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AT liangzheng identificationofimmunotherapyrelatedlncrnasignatureforpredictingprognosisimmunotherapyresponsesanddrugcandidatesinbladdercancer
AT leijia identificationofimmunotherapyrelatedlncrnasignatureforpredictingprognosisimmunotherapyresponsesanddrugcandidatesinbladdercancer
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