ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1527907
Construction and Immunohistochemical Validation of a Necroptosis-Related Prognostic Signature in Bladder Cancer and its Association with Tumor Immune Infiltration
Provisionally accepted
- 1Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
- 2Gansu Provincial Maternal and Child Health Hospital, Lanzhou, Gansu Province, China
- 3Department of Oncology, Ganzhou Cancer Hospital, Ganzhou 341000, Jiangxi Province, China., ganzhou, China
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Background: Bladder urothelial carcinoma (BLCA) represents a highly malignant neoplasm with significant clinical challenges. Necroptosis, a programmed form of cell death, exhibits dual regulatory functions in both tumor immunomodulation and oncogenesis. The precise mechanistic involvement of necroptosis-related genes (NRGs) in BLCA pathogenesis remains poorly characterized, prompting our systematic investigation of their potential biological and clinical significance.We performed comprehensive bioinformatics analyses utilizing integrated datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database.Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, we curated 159 NRGs and subsequently identified 25 differentially expressed genes functionally implicated in necrotic cell death and extrinsic apoptotic pathways. Specifically, including Influenza A signaling, NOD -like receptor cascades, and related biological processes. Univariate Cox proportional hazards modeling coupled with LASSO regression analysis revealed five prognostically significant NRGs (CAMK2A, CHMP4C, IL33, IRF9, and TRAF5). Based on these genes, we developed a robust prognostic model capable of stratifying patients into high-and low-risk categories, each exhibiting distinct survival outcomes. This model demonstrated moderate accuracy in prognosis prediction. Immunohistochemical validation in BLCA specimens confirmed dysregulated expression patterns of these five NRGs.Additional analyses uncovered significant correlations between NRG expression profiles and various immunological parameters, including immune cell infiltration patterns, immune checkpoint molecule expression.Our study delineates a novel five-gene NRGs signature with robust prognostic value in BLCA. These genes determinants appear to critically influence both tumor progression and immune microenvironment, thereby representing promising candidates for therapeutic targeting and future mechanistic exploration in bladder cancer biology.
Keywords: Bladder urothelial carcinoma, necroptosisrelated, Prognostic signature, tumor microenvironment infiltration, Immunohistochemical Validation
Received: 14 Nov 2024; Accepted: 18 Jul 2025.
Copyright: © 2025 Wang, Ding and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kai Sun, Department of Oncology, Ganzhou Cancer Hospital, Ganzhou 341000, Jiangxi Province, China., ganzhou, China
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