Alfahed Abdulaziz
Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Pharmaceuticals (Basel). 2025 Jun 17;18(6):905. doi: 10.3390/ph18060905.
: PARP inhibitors (PARPis) currently play frontline roles in the management of prostate, pancreatic, ovarian and breast cancers, but their roles in colorectal cancer (CRC) management have yet to be clarified. Importantly, the specific predictive biomarkers for PARPis in CRC are still matters of investigations. The aim of this study is to identify the potential predictive biomarkers of PARP inhibition in CRC. : Gene set enrichment analyses (GSEAs) and drug ontology enrichment analyses (DOEAs) of PARPi response gene sets were applied as the surrogates of PARPi response to two CRC cohorts in order to compare the predictive capacities of mutation status, MSI status, as well as and expression for PARP inhibition to those of a homologous repair deficiency surrogate, and large-scale state transition (LST). Differential enrichment score (ES) and ontology enrichment (OE) analyses were used to interrogate the differential correlation of the predictive biomarkers with PARPi response, relative to LST. : The results demonstrated that LST-low, rather than LST-high, CRC subsets exhibited an enrichment of the PARPi response, in contrast to what has been established for other cancers. Furthermore, CRC subsets with wild-type , positive MSI, as well as high and expression exhibited an enrichment of the PARPi response gene sets. Moreover, there was no differential enrichment of the PARPi response between LST and each of the MSI statuses, expression and expression. Furthermore, the preliminary differential enrichment observed between the LST-based and mutation status-based PARPi responses could not be validated with further testing. : MSI status, mutation status as well as and expression may be substitutes for low LST as predictive biomarkers of PARPi response in CRC.
聚（ADP - 核糖）聚合酶抑制剂（PARPis）目前在前列腺癌、胰腺癌、卵巢癌和乳腺癌的治疗中发挥着一线作用，但其在结直肠癌（CRC）治疗中的作用尚未阐明。重要的是，CRC中PARPis的特异性预测生物标志物仍是研究的课题。本研究的目的是确定CRC中PARP抑制的潜在预测生物标志物。对PARPi反应基因集进行基因集富集分析（GSEAs）和药物本体富集分析（DOEAs），作为PARPi对两个CRC队列反应的替代指标，以比较突变状态、微卫星不稳定性（MSI）状态以及[基因名称1]和[基因名称2]表达对PARP抑制的预测能力与同源修复缺陷替代指标和大规模状态转变（LST）的预测能力。使用差异富集分数（ES）和本体富集（OE）分析来探究预测生物标志物与PARPi反应相对于LST的差异相关性。结果表明，与其他癌症的情况相反，LST低而非LST高的CRC亚组表现出PARPi反应的富集。此外，具有野生型[基因名称3]、MSI阳性以及[基因名称1]和[基因名称2]高表达的CRC亚组表现出PARPi反应基因集的富集。此外，LST与MSI状态、[基因名称1]表达和[基因名称2]表达中的每一个之间在PARPi反应上均无差异富集。此外，基于LST和基于[基因名称3]突变状态的PARPi反应之间初步观察到的差异富集在进一步测试中无法得到验证。MSI状态、[基因名称3]突变状态以及[基因名称]和[基因名称2]表达可能作为低LST的替代指标，作为CRC中PARPi反应的预测生物标志物。
