Identification of FLRT2 as a key prognostic gene through a comprehensive analysis of TMB and IRGPs in BLCA patients

Yaling Tao; Yaling Tao; Xiaoling Yu; Huaiwei Cong; Jinpeng Li; Jinpeng Li; Junqi Zhu; Huaxin Ding; Qian Chen; Qian Chen; Qian Chen; Ting Cai; Ting Cai

doi:10.3389/fonc.2023.1229227

Frontiers in Oncology (Feb 2024)

Identification of FLRT2 as a key prognostic gene through a comprehensive analysis of TMB and IRGPs in BLCA patients

Yaling Tao,
Yaling Tao,
Xiaoling Yu,
Huaiwei Cong,
Jinpeng Li,
Jinpeng Li,
Junqi Zhu,
Huaxin Ding,
Qian Chen,
Qian Chen,
Qian Chen,
Ting Cai,
Ting Cai

Affiliations

Yaling Tao: Research Institute, Ningbo No.2 Hospital, Ningbo, China
Yaling Tao: Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
Xiaoling Yu: Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
Huaiwei Cong: Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
Jinpeng Li: Research Institute, Ningbo No.2 Hospital, Ningbo, China
Jinpeng Li: Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
Junqi Zhu: Department of Research and Development, Thorgene Co., Ltd., Beijing, China
Huaxin Ding: Department of Pathology, Ningbo Clinical Pathology Diagnosis Center, Ningbo, China
Qian Chen: Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
Qian Chen: Department of Research and Development, Thorgene Co., Ltd., Beijing, China
Qian Chen: Research Institute, Ningbo Hangzhou Bay Hospital, Ningbo, China
Ting Cai: Research Institute, Ningbo No.2 Hospital, Ningbo, China
Ting Cai: Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China

DOI: https://doi.org/10.3389/fonc.2023.1229227
Journal volume & issue: Vol. 13

Abstract

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IntroductionThe tumor immune environment and immune-related genes are instrumental in the development, progression, and prognosis of bladder cancer (BLCA). This study sought to pinpoint key immune-related genes influencing BLCA prognosis and decipher their mechanisms of action.Methods and resultsWe analyzed differentially expressed genes (DEGs) between high- and low- tumor mutational burden (TMB) groups. Subsequently, we constructed a reliable prognostic model based on immune-related gene pairs (IRGPs) and analyzed DEGs between high- and low-risk groups. A total of 22 shared DEGs were identified across differential TMB and IRGPs-derived risk groups in BLCA patients. Through univariate Cox and multivariate Cox analyses, we highlighted five genes - FLRT2, NTRK2, CYTL1, ZNF683, PRSS41 - significantly correlated with BLCA patient prognosis. Notably, the FLRT2 gene emerged as an independent prognostic factor for BLCA, impacting patient prognosis via modulation of macrophage infiltration in immune microenvironment. Further investigation spotlighted methylation sites - cg25120290, cg02305242, and cg01832662 - as key regulators of FLRT2 expression.DiscussionThese findings identified pivotal prognostic genes in BLCA and illuminated the intricate mechanisms dictating patient prognosis. This study not only presents a novel prognostic marker but also carves out potential avenues for immunotherapy and targeted therapeutic strategies in BLCA. By demystifying the profound impact of immune-related genes and the tumor immune environment, this study augments the comprehension and prognostic management of bladder cancer.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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