22P - Clinical significance of DNA damage response mutations in early stage NSCLC

Background

DNA damage response (DDR) pathways are essential to sustain genomic stability and play a critical role in cancer development and progression. Here, we investigated DDR genes mutations profile in early-stage non-small cell lung cancer (NSCLC) and their prognostic values.

Methods

We first examined 74 DDR genes involved in seven DDR pathways and then focused on six specific genes: ATM, BRCA1/2, CHEK1, BARD1, BRIP1. A total of 179 stage I and IIIa NSCLC patients who received curative resection in Peking Union Medical College Hospital and their corresponding samples were collected for DNA sequencing, immunohistochemistry and survival analysis.

Results

A total of 167 eligible patients were finally analyzed. Mutation frequencies were 82% and 26.3% for the selected 74 genes and 6 genes, respectively. No association was found between DDR gene status and PD-L1 expression, CD8 positive lymphocyte and tumor-associated macrophage (TAM) infiltration in tumor area. Numbers of gene mutations was significantly increased among patients with DDR alterations. Deleterious mutations in ATM, BRCA1/2, CHEK1, BARD1 and BRIP1 were independent prognostic indicators of significantly longer disease-free survival.

Conclusions

Deleterious mutations of these six genes were common in early-stage NSCLC and may serve as prognostic biomarkers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

National High Level Hospital Clinical Research Funding (to MW), Grant/Award Number:2022-PUMCH-B-106.

Disclosure

All authors have declared no conflicts of interest.