Correlation of homologous recombination repair genes with clinical features in non-small cell lung cancer
Objective:To investigae the status of homologous recombination deficiency(HRD)in non-small cell lung cancer(NSCLC)patients by using genomic instability score(GIS)and the correlation of HRD status and homologous recombination repair(HRR)genes with the clinical features of NSCLC.Methods:A total of 335 patients with NSCLC who were treated in The First Affiliated Hospital of Chongqing Medical University from January 2020 to January 2022 were enrolled,and next-generation sequencing was used to measure GIS score and 35 HRR genes.GIS score was determined based on loss of heterozygosity,telomeric allelic imbalance,and large-scale state transition.The Mann-Whitney U test,the Kruskal-Wallis test,and the Dunn-Bonferroni test were used to investigate the correla-tion of GIS score and HRR genes with clinical features.The Spearman analysis was used to investigate the correlation between GIS score and tumor mutation burden(TMB).Results:Among the 335 patients,male sex,older age,advanced stage,smoking history,and squamous cell carcinoma all contributed to a higher GIS score,and the Md(P25,P75)values of GIS scores were 13(4,26.75),12(3,22.5),21.5(12,30),16(4,27),and 24(18,38.25),respectively(Z=-5.083,P＜0.001;Z=2.973,P=0.003;Z=8.225,P＜0.001;Z=4.655,P＜0.001;Z=-7.082,P＜0.001).The GIS score of the samples in the HRR somatic mutation group was significantly higher than that in the wild group,with a Md(P25,P75)value of 18.5(5.25,28.75)and 6(1,16),respectively(Z=5.012,P＜0.00 1).A total of 33 HRR-related gene mutations were found,which were mainly located in the ATM,RECQL4,ATR,FANCM,BRCA1,FANCA,BRIP1,NBN,and WRN genes,and among these genes,mutations in the BRCA2,FANCI,and FANCA genes could lead to the increase in GIS score,with a Md(P25,P75)value of 34(25.25,51),31.5(14.5,50),and 22(12,44),respectively(Z=-2.805,P=0.005;Z=-2.216,P=0.027;Z=-2.478,P=0.013).GIS score was positively correlated with TMB(rs=0.504,P＜0.001).Conclusion:This study reveals GIS score and the characteristics of HRR mutations in Chinese NSCLC patients,and these findings suggest that GIS score and HRR gene detection based on next-generation sequencing can become new bio-markers for targeted therapy and immunotherapy in NSCLC patients.
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