Reverse engineering a predictive signature characterized by proliferation, DNA damage, and immune escape from stage i lung adenocarcinoma recurrence

Jiannan Yao, Xinying Xue, Dongfeng Qu, C. Benedikt Westphalen, Yang Ge, Liyang Zhang, Manyu Li, Tianbo Gao, Parthasarathy Chandrakesan, Kenneth J. Vega, Jun Peng, Guangyu An, Nathaniel Weygant

Research output: Contribution to journalArticlepeer-review

Abstract

Identifying early-stage cancer patients at risk for progression is a major goal of biomarker research. This report describes a novel 19-gene signature (19-GCS) that predicts stage I lung adenocarcinoma (LAC) recurrence and response to therapy and performs comparably in pancreatic adenocarcinoma (PAC), which shares LAC molecular traits. Kaplan-Meier, Cox regression, and cross-validation analyses were used to build the signature from training, test, and validation sets comprising 831 stage I LAC transcriptomes from multiple independent data sets. A statistical analysis was performed using the R language. Pathway and gene set enrichment were used to identify underlying mechanisms. 19-GCS strongly predicts overall survival and recurrence-free survival in stage I LAC (P=0.002 and P<0.001, respectively) and in stage I-II PAC (P<0.0001 and P<0.0005, respectively). A multivariate cox regression analysis demonstrated the independence of 19-GCS from significant clinical factors. Pathway analyses revealed that 19-GCS high-risk LAC and PAC tumors are characterized by increased proliferation, enhanced stemness, DNA repair deficiency, and compromised MHC class I and II antigen presentation along with decreased immune infiltration. Importantly, high-risk LAC patients do not appear to benefit from adjuvant cisplatin while PAC patients derive additional benefit from FOLFIRINOX compared with gemcitabine-based regimens. When validated prospectively, this proof-of-concept biomarker may contribute to tailoring treatment, recurrence reduction, and survival improvements in early-stage lung and pancreatic cancers.

Original languageEnglish (US)
Pages (from-to)638-653
Number of pages16
JournalActa Biochimica et Biophysica Sinica
Volume52
Issue number6
DOIs
StatePublished - Apr 29 2020

Keywords

  • biomarker
  • immunity
  • lung adenocarcinoma
  • pancreatic adenocarcinoma
  • prognosis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Fingerprint Dive into the research topics of 'Reverse engineering a predictive signature characterized by proliferation, DNA damage, and immune escape from stage i lung adenocarcinoma recurrence'. Together they form a unique fingerprint.

Cite this