Open access
Integration of single-cell transcriptomics and genomic mutation analysis identifies an immunotherapy-resistant tumor subcluster and validates ARNTL2 as a malignant driver in lung adenocarcinoma
Z. Qiu
Hui Zhao
Qiong Lyu
Zhigang Li
Qiujiang Xi
Bing-Qing Ye
Qianshan Long
Zheng-Xin Lai
Xiang Cao
W. Zhong
Yu Zhang
Rongrong Liu
Medicine
Abstract
Highlights • Single-cell sequencing reveals resistance-linked malignant subcluster in LUAD.• Cluster 2 shows hyperproliferative reprogramming with KRT17, S100A2, CST6 upregulation.• CoxBoost + survivalSVM model achieves optimal C-index of 0.686 across seven cohorts.• Low-risk patients exhibit greater immune infiltration and higher immunotherapy scores.• ARNTL2 knockdown suppresses proliferation and invasion, confirming oncogenic role.