Ferroptosis-related lncRNAs: Distinguishing heterogeneity of the tumour microenvironment and predicting immunotherapy response in bladder cancer

Zhan Yang; Xiaoqi Li; Lijun Zhou; Yaxian Luo; Ning Zhan; Yifan Ye; Zhichao Liu; Xiaoting Zhang; Tao Qiu; Lining Lin; Lianjie Peng; Yiming Hu; Chaoran Pan; Mouyuan Sun; Yan Zhang

Heliyon (Jun 2024)

Ferroptosis-related lncRNAs: Distinguishing heterogeneity of the tumour microenvironment and predicting immunotherapy response in bladder cancer

Zhan Yang,
Xiaoqi Li,
Lijun Zhou,
Yaxian Luo,
Ning Zhan,
Yifan Ye,
Zhichao Liu,
Xiaoting Zhang,
Tao Qiu,
Lining Lin,
Lianjie Peng,
Yiming Hu,
Chaoran Pan,
Mouyuan Sun,
Yan Zhang

Affiliations

Zhan Yang: Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Xiaoqi Li: Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Lijun Zhou: Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Yaxian Luo: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
Ning Zhan: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
Yifan Ye: Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Zhichao Liu: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
Xiaoting Zhang: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
Tao Qiu: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
Lining Lin: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
Lianjie Peng: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
Yiming Hu: Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Chaoran Pan: Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Mouyuan Sun: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China; Corresponding author.
Yan Zhang: Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Corresponding author.

Journal volume & issue: Vol. 10, no. 11
p. e32018

Abstract

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Ferroptosis, a cell death pathway dependent on iron, has been shown in research to play a role in the development, advancement, and outlook of tumours through ferroptosis-related lncRNAs (FRLRs). However, the value of the FRLRs in bladder cancer (BLCA) has not been thoroughly investigated. This research project involved developing a predictive model using ten specific FRLRs (AC099850.4, AL731567.1, AL133415.1, AC021321.1, SPAG5-AS1, HMGA2-AS1, RBMS3-AS3, AC006160.1, AL583785.1, and AL662844.4) through univariate COX and LASSO regression techniques. The validation of this signature as a standalone predictor was confirmed in a group of 65 patients from the urology bladder tumour database at the First Affiliated Hospital of Wenzhou Medical University in Wenzhou, China. Patients were categorized based on their median risk score into either a low-risk group or a high-risk group. Enrichment analysis identified possible molecular mechanisms that could explain the variations in clinical outcomes observed in high-risk and low-risk groups. Moreover, we explored the correlation between FLPS and immunotherapy-related indicators. The ability of FLPS to forecast the effectiveness of immunotherapy was validated by the elevated levels of immune checkpoint genes (PD-L1, CTLA4, and PD-1) in the group at high risk. We also screened the crucial FRLR (HMGA2-AS1) through congruent expression and prognostic conditions and established a ceRNA network, indicating that HMGA2-AS1 may affect epithelial-mesenchymal transition by modulating the Wnt signalling pathway through the ceRNA mechanism. We identified the top five mRNAs (NFIB, NEGR1, JAZF1, JCAD, and ESM1) based on random forest algorithm and analysed the relationship between HMGA2-AS1, the top five mRNAs, and immunotherapy, and their interactions with drug sensitivities. Our results suggest that patients with BLCA have a greater sensitivity to four drugs (dasatinib, pazopanib, erismodegib and olaparib). Our study provides new insights into the TME, key signalling pathways, genome, and potential therapeutic targets of BLCA, with future guidance for immunotherapy and targeted precision drugs.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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