Aging-related transcriptomic signatures associated with recurrence following resection of stage I lung adenocarcinoma
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Age is an independent prognostic factor in early-stage non-small cell lung cancer (NSCLC), yet the molecular differences between old and young patients and their contribution to disease progression remain unclear. We investigated age-related transcriptomic differences in early-stage lung adenocarcinoma (LUAD) and their association with recurrence. Methods: Tumor and adjacent normal lung tissue (NAT) from 126 stage I LUAD patients underwent bulk RNA sequencing to characterize age-related transcriptomic profiles. Differential expression and multiscale embedded gene co-expression network analysis (MEGENA) were used to identify age- and recurrence-associated modules. Pathways were annotated using Ingenuity Pathway Analysis. External confirmation was performed using TCGA (n=256) and TRACERx (n=83) cohorts. Results: Based on the cohort's median age, 60 patients were classified as old (>70 years) and 66 as young (≤70 years). In tumors, older patients with recurrence showed marked upregulation of cancer-associated, inflammatory, and extracellular matrix pathways compared with older patients without recurrence. In NAT samples, older patients with recurrence demonstrated upregulation of inflammatory and cancer-associated pathways-including phagosome formation, IL-17, IL-6, and Th2 signaling-that were absent or downregulated in young patients. MEGENA revealed a larger number of recurrence-associated co-expression modules in old versus young patients. These age-related patterns were highly conserved in both external cohorts across tumor and NAT samples. Conclusion: Aging in LUAD is associated with distinct cancer- and inflammation-related transcriptomic alterations that contribute to recurrence. Aging-related molecular signatures may improve risk stratification for early-stage lung cancer. Impact: Aging shapes tumor microenvironment transcriptomes in stage I LUAD, enabling improved relapse risk stratification after surgery.
Source: npj Aging
Authors: Fares Darawshy, Cigdem Sevim Bayrak, Xianxiao Zhou, Kendrew Wong, Imran Sulaiman, Benjamin Kwok, Cecilia Chung, Alena Lukovnikova, Sofia Roldan, Benjamin G. Wu, Matthias C. Kugler, Yonghua Li, Rosemary Schluger, Destiny Collazo, Yaa Kyeremateng, Ray Pillai, Matthew Blaisdsell, Michelle Fridman, Alexander Bain, Marcus D. Goncalves, Chandra Goparaju, Daniel Sterman, Anil Vachani, Gregory David, Aristotelis Tsirigos, Bin Zhang, Christian V. Forst, Harvey Pass, Leopoldo N. Segal, Jun-Chieh J. Tsay
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,690
Funders: Hadassah Medical Organization, Royal College of Surgeons in Ireland, York University, Hebrew University of Jerusalem, National Institutes of Health, School of Medicine, New York University, NYU Grossman School of Medicine, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences
OpenAlex ID: W7204463100