Single cell RNA-seq and bulk RNA-seq analysis identifies MUC1 as a key gene for lung adenocarcinoma to neuroendocrine transformation

作者：Hongxia Li, Tiantian Yang, Yu Chen, Zhiqin Xie · 发表于：Translational Lung Cancer Research · 年份：2025 · DOI：10.21037/tlcr-24-806 · 被引用次数：4 · 研究领域：Macrophage Migration Inhibitory Factor、Microbial metabolism and enzyme function、GDF15 and Related Biomarkers

Background: Tyrosine kinase inhibitors (TKIs) have demonstrated significant effectiveness in treating advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Despite initial success, resistance to EGFR-TKIs inevitably occurs. One observed phenomenon in resistant lung cancers is the histological transformation from NSCLC to neuroendocrine carcinoma (NEC). The objective of this study is to explore and delineate the genetic and immune features linked to the transition from lung adenocarcinoma (LUAD) to NEC. Methods: Bulk RNA-sequencing and Mendelian randomization (MR) analysis were utilized to identify candidate genes associated with the progression from LUAD to NEC. Expression quantitative trait locus data from publicly available databases were leveraged to pinpoint key genes in relevant tissues. Furthermore, the immune microenvironment was explored using weighted gene co-expression network analysis (WGCNA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) databases. Single-cell RNA sequencing data from 16,765 cells across six tissue biopsy samples of LUAD and NEC were scrutinized to investigate cell interaction networks during histological transformation. The molecular pathways involved in dynamic cellular processes were elucidated through the analysis of cellular communication and pseudotime trajectory. Results: Through the use of RNA-sequencing and MR analysis, it was determined that mu...