现代妇产科进展2025，Vol.34Issue(9)：655-663,9.DOI:10.13283/j.cnki.xdfckjz.2025.09.030
全基因组文库筛选鉴定PARP抑制剂敏感性基因的整合分析
Integrated analysis of whole-genome library screening to identify genes associated with PARP inhibitor sensitivity
摘要
Abstract
Objective:To integrate published data using CRISPR-Cas9 library screen-ing technology,develop a standardization and integration method,reveal genes associated with PARPi sensitivity on a genome-wide scale,and construct a transcriptome-based prediction mod-el.Methods:CRISPR-Cas9 whole-genome knockout library screening data based on human tumor cell models were included,and standardized Z-scores were obtained after reanalysis.The standard Z-scores were merged using a random effects model,and a PARPi sensitivity score(PSS)was constructed based on the integrated Z-scores.The PSS and tumor metabolism score were calculated using transcriptome data of pan-cancer tumor cell lines,and the homologous re-combination repair deficiency(HRD)score was used to evaluate the genomic stability of tumor cell lines.Results:A total of 21 library screening data from 9 studies were included.Correlation analysis showed that the consistency between different data sets was relatively low.Through inte-grated analysis,it was found that genes such as PARP1,E2F7,and TP53BP1 were positively correlated with PARPi sensitivity,while genes such as PSMC3IP,ATM,and RAD51B were asso-ciated with PARPi resistance.The relationship between the integrated Z-score and PARPi sensi-tivity was verified in PARPi-resistant cell lines.The enrichment analysis of the whole genome integrated Z-score showed that the ranking of PARPi-sensitive genes was significantly negatively correlated with the homologous recombination repair function.Based on the integrated Z-scores of significant genes,the PSS was constructed,which can effectively predict the activity of homol-ogous recombination repair and the stability of the tumor genome.In tumor cell lines and clini-cal samples,the PSS was significantly positively correlated with HRD.Conclusion:By integra-ting and analyzing the whole genome library screening data,this study identified genes associat-ed with PARPi sensitivity,providing potential biomarkers for future personalized medicine and drug development.The PSS prediction model constructed based on this data has similar clinical significance as the HRD score.关键词
PARP抑制剂/肿瘤细胞系/文库筛选/同源重组修复/预测模型Key words
PARP inhibitors/Tumor cell lines/Library screening/Homologous recom-bination repair/Predictive model分类
医药卫生引用本文复制引用
朱幼梅,林仲秋,卢淮武,李鸣浩,彭宣玮,程傲霜..全基因组文库筛选鉴定PARP抑制剂敏感性基因的整合分析[J].现代妇产科进展,2025,34(9):655-663,9.基金项目
北京康华中西医发展基金会,横向项目(No:KH-2021-LQJJ-010) （No:KH-2021-LQJJ-010）
