Journal
THORACIC CANCER
Volume 12, Issue 15, Pages 2170-2181Publisher
WILEY
DOI: 10.1111/1759-7714.14046
Keywords
biomarker; neoantigen load; NSCLC; prognosis; whole exome sequencing
Categories
Funding
- Natural Science Foundation of Zhejiang Province [LQ21H160004]
- Zhejiang Medical technology program [202143913]
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In Chinese patients, higher neoantigen load (NAL) was associated with improved disease-free survival (DFS) in squamous cell lung carcinoma (SCC) patients, but not in lung adenocarcinoma (ADC) patients. A benefit from adjuvant chemotherapy was correlated with lower NAL. Other genomic factors did not show prognostic or predictive value for DFS in SCC or ADC patients.
Background The prognosis for patients with stage II/III non-small cell lung cancer (NSCLC) is unsatisfactory, even after complete tumor resection and adjuvant chemotherapy. Here, we assessed the prognostic and predictive value of immunogenomic signatures for stage II/III NSCLC in Chinese patients. Methods A total of 91 paired resected stage II/III NSCLC and normal tissues, including 47 squamous cell lung carcinomas (SCC) and 44 lung adenocarcinomas (ADC), were collected and analyzed using whole exome sequencing (WES) to identify immunogenomic signatures for association with clinicopathological variables and disease-free survival (DFS). Results Higher neoantigen load (NAL, >2 neoantigens/Mb) exhibited better DFS for SCC patients (p = 0.021) but not ADC patients. A benefit from adjuvant chemotherapy was correlated with lower NAL (<= 2 neoantigens/Mb) (p = 0.009). However, tumor mutation burden (TMB), mutations of individual gene, oncogene pathways, and antigen presentation machinery genes, and human leukocyte antigen (HLA)-I number and HLA-I loss of heterozygosity (LOH) had no prognostic or predictive value for DFS of SCC or ADC patients. Conclusions NAL is a useful biomarker for lung SCC prognosis and prediction of chemotherapy responses in Chinese patients. The predictive value of NAL for adjuvant immunotherapy should be further explored in patients with resected NSCLC.
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