文章：

结直肠癌中ABCC4与ABCG2高表达亚群的特征——预测治疗反应的新机遇

Characteristics of ABCC4 and ABCG2 High Expression Subpopulations in CRC—A New Opportunity to Predict Therapy Response

原文发布日期：28 November 2023

DOI: 10.3390/cancers15235623

类型: Article

开放获取: 是

英文摘要：

Background: Our previous findings proved that ABCC4 and ABCG2 proteins present much more complex roles in colorectal cancer (CRC) than typically cancer-associated functions as drug exporters. Our objective was to evaluate their predictive/diagnostic potential. Methods: CRC patients’ transcriptomic data from the Gene Expression Omnibus database (GSE18105, GSE21510 and GSE41568) were discriminated into two subpopulations presenting either high expression levels of ABCC4 (ABCC4 High) or ABCG2 (ABCG2 High). Subpopulations were analysed using various bioinformatical tools and platforms (KEEG, Gene Ontology, FunRich v3.1.3, TIMER2.0 and STRING 12.0). Results: The analysed subpopulations present different gene expression patterns. The protein–protein interaction network of subpopulation-specific genes revealed the top hub proteins in ABCC4 High: RPS27A, SRSF1, DDX3X, BPTF, RBBP7, POLR1B, HNRNPA2B1, PSMD14, NOP58 and EIF2S3 and in ABCG2 High: MAPK3, HIST2H2BE, LMNA, HIST1H2BD, HIST1H2BK, HIST1H2AC, FYN, TLR4, FLNA and HIST1H2AJ. Additionally, our multi-omics analysis proved that the ABCC4 expression correlates with substantially increased tumour-associated macrophage infiltration and sensitivity to FOLFOX treatment. Conclusions: ABCC4 and ABCG2 may be used to distinguish CRC subpopulations that present different molecular and physiological functions. The ABCC4 High subpopulation demonstrates significant EMT reprogramming, RNA metabolism and high response to DNA damage stimuli. The ABCG2 High subpopulation may resist the anti-EGFR therapy, presenting higher proteolytical activity.

摘要翻译： 

背景：我们先前的研究证实，ABCC4与ABCG2蛋白在结直肠癌（CRC）中的作用远比其作为药物外排蛋白的典型癌症相关功能更为复杂。本研究旨在评估其预测与诊断潜力。方法：从基因表达综合数据库（GSE18105、GSE21510和GSE41568）获取结直肠癌患者转录组数据，根据ABCC4高表达（ABCC4 High）或ABCG2高表达（ABCG2 High）分为两个亚群。运用多种生物信息学工具与平台（KEGG、基因本体论、FunRich v3.1.3、TIMER2.0及STRING 12.0）对亚群进行分析。结果：分析显示两个亚群具有不同的基因表达模式。亚群特异性基因的蛋白质相互作用网络揭示：ABCC4 High亚群的核心枢纽蛋白包括RPS27A、SRSF1、DDX3X、BPTF、RBBP7、POLR1B、HNRNPA2B1、PSMD14、NOP58和EIF2S3；ABCG2 High亚群则包括MAPK3、HIST2H2BE、LMNA、HIST1H2BD、HIST1H2BK、HIST1H2AC、FYN、TLR4、FLNA和HIST1H2AJ。此外，多组学分析证实ABCC4表达与肿瘤相关巨噬细胞浸润显著增加及对FOLFOX方案敏感性增强相关。结论：ABCC4与ABCG2可用于区分具有不同分子与生理功能的结直肠癌亚群。ABCC4 High亚群表现出显著的上皮间质转化重编程、RNA代谢活跃及对DNA损伤刺激的高反应性；ABCG2 High亚群则可能通过更高的蛋白水解活性抵抗抗EGFR治疗。

原文链接：

Characteristics of ABCC4 and ABCG2 High Expression Subpopulations in CRC—A New Opportunity to Predict Therapy Response