Correlation of homologous recombination repair genes with clinical features in non-small cell lung cancer

Yang Xi, Zhao Jie, Tang Haitao, Liao Xin, Mou Kang, Li Xiaosong, Shen Yifan

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Journal of Chongqing Medical University ›› 2024, Vol. 49 ›› Issue (07) : 871-876. DOI: 10.13406/j.cnki.cyxb.003508
Clinical research

Correlation of homologous recombination repair genes with clinical features in non-small cell lung cancer

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Abstract

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 correlation 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<0.001）. 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 biomarkers for targeted therapy and immunotherapy in NSCLC patients.

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non-small cell lung cancer / homologous recombination deficiency / genomic instability score / homologous recombination repair

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Yang Xi , Zhao Jie , Tang Haitao , et al . Correlation of homologous recombination repair genes with clinical features in non-small cell lung cancer. Journal of Chongqing Medical University. 2024, 49(07): 871-876 https://doi.org/10.13406/j.cnki.cyxb.003508

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