Multi-omics analyses reveal biological and clinical insights in recurrent stage I non-small cell lung cancer

Chengdi Wang ^1,2, Jingwei Li ^3,4, Jingyao Chen ^3,4

¹Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China. chengdi_wang@scu.edu.cn.
²Laboratory of Precision Therapeutics, Targeted Tracer Research and Development Laboratory, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. chengdi_wang@scu.edu.cn.
³Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁴Laboratory of Precision Therapeutics, Targeted Tracer Research and Development Laboratory, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁵Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining, China.
⁶State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Chengdu, Sichuan, China.
⁷Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China. zhangli7375@scu.edu.cn.
⁸Laboratory of Precision Therapeutics, Targeted Tracer Research and Development Laboratory, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. zhangli7375@scu.edu.cn.
⁹Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China. weimi003@scu.edu.cn.
¹⁰Laboratory of Precision Therapeutics, Targeted Tracer Research and Development Laboratory, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. weimi003@scu.edu.cn.

⁰Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China. chengdi_wang@scu.edu.cn.

Nature Communications +

|

February 10, 2025

View abstract on PubMed

Summary

Recurrence in stage I non-small cell lung cancer (NSCLC) is linked to specific gene changes and tumor microenvironments. Understanding these molecular drivers can improve treatment strategies for NSCLC patients.

Area Of Science

Oncology
Genomics
Molecular Biology

Background

Stage I non-small cell lung cancer (NSCLC) has high post-operative recurrence rates (20-40%).
Molecular mechanisms driving NSCLC recurrence remain poorly understood.

Purpose Of The Study

To investigate the genomic, epigenomic, and transcriptomic profiles of stage I NSCLC patients to identify factors associated with post-operative recurrence.
To elucidate the molecular mechanisms and tumor ecosystem contributing to NSCLC recurrence.

Main Methods

Generated multi-omics profiles (genomic, epigenomic, transcriptomic) from paired tumor and adjacent tissues of 122 stage I NSCLC patients.
Integrated analyses to identify associations between molecular features, histological subtypes, and recurrence.
Investigated the role of PRAME in metastasis and characterized the tumor microenvironment in recurrent LUAD.

Main Results

Solid/micropapillary subtypes, genomic instability, and APOBEC signature correlate with recurrence.
TP53 mutations and DNA hypomethylation (especially of PRAME) are linked to recurrence.
PRAME inhibition reduces metastasis; recurrent LUAD shows specific immune cell enrichment and altered interactions.

Conclusions

Multi-omics data reveals key molecular drivers and ecosystem features of stage I NSCLC recurrence.
Identified PRAME as a potential therapeutic target for reducing metastasis.
Multi-omics clustering stratifies patients by recurrence risk and suggests targeted therapies.

Related Concept Videos

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...