Relapse-related molecular signature in early-stage lung adenocarcinomas based on base excision repair, stimulator of interferon genes pathway and tumor-infiltrating lymphocytes

Abstract

Approximately 30% of patients with early-stage non-small cell lung cancer (NSCLC) relapse within 5 years after surgery. Therefore, it is necessary to identify a robust and reliable prognostic signature for early-stage NSCLC. Immunohistochemistry data from 147 patients with stage I lung adenocarcinoma (stage I-LUAD) were analyzed for the protein expression of base excision repair (BER), stimulator of interferon genes (STING) and tumor-infiltrating lymphocytes (TIL) to explore the relationship between protein expression and prognosis. A prediction model was further established by nomogram and externally verified using The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. XRCC1 and H2AX are negative prognostic markers for relapse-free survival (RFS), while CD8, CD20 and STING are positive prognostic markers for RFS. Nomograms for RFS share common prognostic markers, including XRCC1, H2AX, STING, CD8 and CD20. The c-index was 0.724 and 0.698 in the training cohort and the internal validation cohort, respectively. It was externally verified that the nomogram model had a good prediction for recurrence of stage I-LUAD. Correlation analysis showed that APE1 and H2AX were negatively correlated with STING, while STING was positively correlated with TIL. BER, the STING pathway and TIL were associated with early recurrence and were correlated with the tissue expression of stage I-LUAD. Our nomogram model was a good predictor for recurrence of stage I-LUAD.

Keywords: BER; STING; TIL; lung adenocarcinoma; nomogram; predictive; recurrence.