Identification of Two Subtypes with Distinct Immune Features in Lung Adenocarcinoma by Utilizing Immune and Metabolism-Related Genes to Assist Immunotherapy

Identification of Two Subtypes with Distinct Immune Features in Lung Adenocarcinoma by Utilizing Immune and Metabolism-Related Genes to Assist Immunotherapy

Mengna Wang¹ and Hongbo Xia¹

¹Department of Respiratory Medicine, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China

This work was designed to explore the value of immune and metabolism-related genes (IMRGs) in lung adenocarcinoma (LUAD) prognosis, with the intention of aiding the application of immunotherapy in LUAD patients. Differential gene expression analysis was conducted using The Cancer Genome Atlas (TCGA)-LUAD data. After merging and deduplication, an intersection was taken with LUAD differential genes to acquire IMRGs. 716 IMRGs were utilized for LUAD clustering, resulting in the stratification of LUAD patients into two subtypes. Cluster-1 demonstrated higher immunophenoscore and lower tumor immune dysfunction and exclusion scores, indicating that cancer patients in cluster-1 were more likely to benefit from immune checkpoint inhibitor therapy. Somatic mutation analysis revealed higher mutation rates in both sample and gene levels for cluster-2 compared to cluster-1. Additionally, we predicted ten prospective candidate drugs, including Teniposide and phloretin, for LUAD patients. LUAD was stratified into two subtypes with distinct molecular features based on IMRGs. These subtypes exhibited pronounced differences in immune processes, checkpoints, genetic mutations, and drug sensitivity. Our endeavor has furnished invaluable insights into comprehending the molecular characteristics of LUAD, potentially enhancing the precision of immunotherapeutic strategies tailored for LUAD.

Key words —— immune-related genes; lung adenocarcinoma; metabolism-related genes; molecular features; prognosis

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Tohoku J. Exp. Med., 2025 May, 266(1), 1-9.

Correspondence: Hongbo Xia, Department of Respiratory Medicine, Affiliated Xiaoshan Hospital, Hangzhou Normal University, No.728, Yucai North Road, Chengxiang Town, Xiaoshan District, Hangzhou City, Zhejiang Province 311200, China.

e-mail: hongbxia@163.com