RUNX1启动子rs2071029多态性对辅助化疗诱导的结直肠癌中性粒细胞减少的易感性

IF 1.9 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Biomarkers in medicine Pub Date : 2025-06-01 Epub Date: 2025-06-10 DOI:10.1080/17520363.2025.2516996
Xikai Luo, Hao Wang, Zhe Huang, Zhuocheng Lin, Chunpeng Li, Qiwen Wang, Yisheng Wei
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引用次数: 0

摘要

目的:探讨RUNX1启动子多态性与辅助化疗诱导的结直肠癌(CRC)中性粒细胞减少症(CIN)的易感性。方法:采用SnaPshot基因分型和Sanger测序对RUNX1启动子多态性rs2071029和rs12626613进行基因分型。采用卡方检验和多因素logistic回归模型分析204例结直肠癌患者rs2071029与CIN的相关性。荧光素酶法分析rs2071029多态性对RUNX1启动子活性的影响。结果:Rs2071029和rs12626613位点存在强连锁不平衡(D ' = 0.957);r2 = 0.878)。与rs2071029 CC基因型相比,TT (OR = 0.250, 95% CI: 0.101 ~ 0.617)发生严重CIN的风险降低。与mFOLFOX6和基线中性粒细胞计数2-4 × 109/L相比,Xelox (OR = 0.169, 95% CI: 0.054 ~ 0.531)和>4 × 109/L(OR = 0.446 95% CI: 0.209 ~ 0.952)分别降低了严重CIN的风险。Rs2071029T启动子活性显著高于rs2071029C启动子(p = 0.014)。分层分析显示,rs2071029 TT的保护作用在60岁以上患者(OR = 0.139, 95% CI: 0.031-0.622)和II期患者(OR = 0.117, 95% CI: 0.018-0.745)中更为明显。结论:RUNX1启动子rs2071029多态性可作为CRC CIN的独立生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Susceptibility of RUNX1 promoter rs2071029 polymorphism to adjuvant chemotherapy-induced neutropenia in CRC.

Aim: To investigate the susceptibility of Runt-related transcription factor 1 (RUNX1) promoter polymorphism to adjuvant chemotherapy-induced neutropenia (CIN) of colorectal cancer (CRC).

Methods: RUNX1 promoter polymorphisms rs2071029 and rs12626613 were genotyped by SnaPshot genotyping and Sanger sequencing. The association of rs2071029 and CIN in 204 CRC patients was analyzed using chi-square test and multivariate logistic regression model. The impact of rs2071029 polymorphism on RUNX1 promoter activity was analyzed by luciferase assay.

Results: Rs2071029 and rs12626613 loci were in strong linkage disequilibrium (D ' = 0.957. r2 = 0.878). Compared with rs2071029 CC genotype, TT (OR = 0.250, 95% CI: 0.101∼0.617) had a decreased risk of severe CIN. Compared with mFOLFOX6,and baseline neutrophil counts 2-4 × 109/L, Xelox (OR = 0.169, 95% CI: 0.054∼0.531) and >4 × 109/L(OR = 0.446 95% CI: 0.209∼0.952) had a decreased risk of severe CIN, respectively. Rs2071029T promoter activity was significantly higher than that of rs2071029C promoter (p = 0.014). Stratified analyses revealed that the protective effect of the rs2071029 TT was more pronounced in patients over 60 years (OR = 0.139, 95% CI: 0.031-0.622) and stage II cases (OR = 0.117, 95% CI: 0.018-0.745).

Conclusion: RUNX1 promoter rs2071029 polymorphism could be useful as an independent biomarker for CIN in CRC.

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来源期刊
Biomarkers in medicine
Biomarkers in medicine 医学-医学:研究与实验
CiteScore
3.80
自引率
4.50%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Biomarkers are physical, functional or biochemical indicators of physiological or disease processes. These key indicators can provide vital information in determining disease prognosis, in predicting of response to therapies, adverse events and drug interactions, and in establishing baseline risk. The explosion of interest in biomarker research is driving the development of new predictive, diagnostic and prognostic products in modern medical practice, and biomarkers are also playing an increasingly important role in the discovery and development of new drugs. For the full utility of biomarkers to be realized, we require greater understanding of disease mechanisms, and the interplay between disease mechanisms, therapeutic interventions and the proposed biomarkers. However, in attempting to evaluate the pros and cons of biomarkers systematically, we are moving into new, challenging territory. Biomarkers in Medicine (ISSN 1752-0363) is a peer-reviewed, rapid publication journal delivering commentary and analysis on the advances in our understanding of biomarkers and their potential and actual applications in medicine. The journal facilitates translation of our research knowledge into the clinic to increase the effectiveness of medical practice. As the scientific rationale and regulatory acceptance for biomarkers in medicine and in drug development become more fully established, Biomarkers in Medicine provides the platform for all players in this increasingly vital area to communicate and debate all issues relating to the potential utility and applications. Each issue includes a diversity of content to provide rounded coverage for the research professional. Articles include Guest Editorials, Interviews, Reviews, Research Articles, Perspectives, Priority Paper Evaluations, Special Reports, Case Reports, Conference Reports and Company Profiles. Review coverage is divided into themed sections according to area of therapeutic utility with some issues including themed sections on an area of topical interest. Biomarkers in Medicine provides a platform for commentary and debate for all professionals with an interest in the identification of biomarkers, elucidation of their role and formalization and approval of their application in modern medicine. The audience for Biomarkers in Medicine includes academic and industrial researchers, clinicians, pathologists, clinical chemists and regulatory professionals.
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