ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1509222
This article is part of the Research TopicHarnessing Big Data for Precision Medicine: Revolutionizing Diagnosis and Treatment StrategiesView all 40 articles
Prognostic significance of calcium-related genes in lung adenocarcinoma and the role of TNNC1 in macrophage polarization and erlotinib resistance
Provisionally accepted
- 1Department of Thoracic Surgery, Suzhou Dushu Lake Hospital, Suzhou, China
- 2Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
- 3Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu Province, China
- 4Department of Respiratory Medicine, Nanjing Second Hospital, Nanjing 210000, China., Nanjing, Liaoning Province, China
- 5Jurong People's Hospital, Jurong, China
- 6Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China., Nanjing, Liaoning Province, China
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Background: Calcium signaling is critical in tumorigenesis. This study analyzed the characteristics of a calcium-related prognostic genes (CRPGs) signature in lung adenocarcinoma (LUAD) for prognostic value and explored TNNC1 as a potential therapeutic target for erlotinib resistance.Methods: Clinical and RNA sequencing data from LUAD patients were obtained from the TCGA and GEO databases. CRPGs were identified through univariate Cox and Kaplan-Meier survival analyses. Calcium-related subtypes were determined via unsupervised clustering. A prognostic signature was constructed and validated using external datasets. Differences in immune infiltration and potential mechanisms in LUAD were explored using seven algorithms. The relationship between signature genes, chemotherapy sensitivity, and potential targeted therapies was evaluated. Potential drug targets were identified using Mendelian randomization (MR) and phenome-wide association studies (PheWAS). The association between TNNC1, erlotinib resistance, and macrophage M2 polarization was investigated through in vitro experiments.The study identified 33 CRPGs and four subtypes among LUAD patients. The prognostic signature, comprising nine CRPGs, accurately predicted 1-, 2-, and 3-year overall survival. TNNC1 was identified as a crucial tumor suppressor gene and potential drug target. Down-regulation of TNNC1 decreased the IC50 value of erlotinib in LUAD cells and inhibited macrophage M2 polarization.This study developed a reliable prognostic signature based on nine CRPGs for predicting LUAD patient outcomes. TNNC1 may enhance LUAD cell resistance to erlotinib through macrophage polarization to the M2 phenotype.
Keywords: lung adenocarcinoma1, calcium-related genes2, prognostic signature3, TNNC14, erlotinib resistance5, macrophage M2 polarization6
Received: 10 Oct 2024; Accepted: 22 Apr 2025.
Copyright: © 2025 Xie, Feng, Chen, Wang, Yao, Min and Luo. 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 Xie, Department of Thoracic Surgery, Suzhou Dushu Lake Hospital, Suzhou, China
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