Comutations in DDR related pathways may serve as potential predictors for Immune checkpoint blockades (ICB) therapy, providing a potentially convenient approach for future clinical practice.
Genomic alterations were determined by OncoDrug-SeqTM603-gene panel assay through next generation sequencing (NGS). Patients who harbored mutations in both homologous recombination repair (HRR) and mismatch repair (MMR) pathways were enrolled in group A. Patients who harbored mutations in only HRR pathway were enrolled in group B. Patients who harbored mutations in only MMR pathway were enrolled in group C.
Totally, samples from 1309 patients were collected for NGS assay, 691patients (52.7%) were found to harbor at least one variant in DDR related pathways. The top 10 genes with high frequency were EGFR (42.2%), TP53(41.6%), FAT3 (28.2%), KMT2C (25.5%), PDE4DIP (25.6%), FAT1 (21.5%), KMT2D (25.5%), OBSL1 (20.8%), SYNE1 (16.3), and ROS1 (5.5%). Complete data were obtained from 687 patients, including 462 tissue samples and 225 blood samples. Correlated results were obtained in both blood samples and tissue samples. Comutation status was associated with both higher TMB and TNB. Among the three groups, group A had the highest TMB (mean value: 8 mut/Mb). In the other two groups, TMB was 6 mut/Mb in group B, and 5.3 mut/Mb in group C (p=0.000016), respectively. TNB in group A (mean value: 5.9 mut/Mb) was the highest among the three groups with significantly statistical difference (p=0.00026) detected in tissue samples. TNB in group A (mean value: 2.7mut/Mb) was the highest among the three groups detected in blood samples, but with no statistical difference. Table: 172MO
|TMB sorting||A vs B vs C||(p=0.000016)||TMB sorting||A vs B vs C||(p=0.000012)|
|TNB sorting||A vs B vs C||(p=0.00026)||TNB sorting||B vs C vs A||(p=0.19)|
|PDL1 sorting||C vs B vs A||(p=0.003)|
We found that pathogenic DDR changes occurred frequently in lung cancer. Patients who harbored comutation in both MMR and HRR had higher levels of TMB and TNB. Our study suggested that mutations in DDR related pathways were worth for further study in its potential for lung cancer.
Legal entity responsible for the study
Shanghai Topgen Biomedical Technology Co., Ltd.
Has not received any funding.
J. Xu: Other, Personal and Institutional, Full or part-time Employment: Shanghai Topgen Biomedical Technology Co., Ltd. C.R. Xia, S. Ding: Other, Personal, Full or part-time Employment: Shanghai Topgen Biomedical Technology Co., Ltd. P. Luo: Other, Personal, Member of the Board of Directors: Shanghai Topgen Biomedical Technology Co., Ltd. All other authors have declared no conflicts of interest.