Genetic Determinants of Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer Identified by Whole Exome Sequencing.

IF 1.2 4区生物学 Q4 GENETICS & HEREDITY

Annals of Human Genetics Pub Date : 2025-07-31 DOI:10.1111/ahg.70019

Jelena Peric, Sandra Dragicevic, Marko Miladinov, Aleksandra Djikic Rom, Jasna Bjelanovic, Jelena Kovac, Jovana Despotovic, Tamara Babic, Jelena Ljubicic, Dunja Pavlovic, Jovana Rosic Stojkovic, Ivan Dimitrijevic, Goran Barisic, Velimir Markovic, Aleksandra Nikolic

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引用次数: 0

Abstract

Background: Neoadjuvant chemoradiotherapy (nCRT) is essential for treating locally advanced rectal cancer (LARC), however response to nCRT varies, and reliable predictors are lacking.

Methods: This study used whole exome sequencing analysis to investigate genetic differences between tumors highly responsive and non-responsive to nCRT. Five patients with good response and two patients without response to nCRT were used as a discovery set.

Results: The analysis identified 15 InDels and 202 non-synonymous SNVs exclusively present in tumors of non-responders, mainly in genes regulating the cell cycle, adhesion, and migration. In contrast, 9 InDels and 122 non-synonymous SNVs were exclusively present in tumors of good responders, primarily in extracellular matrix remodeling and immunity-related genes. Six variants in transmembrane transporter genes were selected as candidate biomarkers and validated in 33 LARC patients.

Conclusion: The results suggest that SLC16A6 rs7222013 and SLC25A2 rs3749780 may serve as potential predictors of poor nCRT response in LARC patients.

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全外显子组测序鉴定直肠癌对新辅助放化疗反应的遗传决定因素。

背景：新辅助放化疗（nCRT）对于治疗局部晚期直肠癌（LARC）至关重要，然而对nCRT的反应各不相同，缺乏可靠的预测指标。方法：本研究采用全外显子组测序分析，研究对nCRT高反应和无反应肿瘤的遗传差异。5例对nCRT反应良好的患者和2例无反应的患者作为发现组。结果：分析发现15个indel和202个非同义snv只存在于无应答的肿瘤中，主要存在于调节细胞周期、粘附和迁移的基因中。相比之下，9个InDels和122个非同义snv仅存在于良好应答的肿瘤中，主要存在于细胞外基质重塑和免疫相关基因中。选择跨膜转运蛋白基因的6个变异作为候选生物标志物，并在33例LARC患者中进行了验证。结论：SLC16A6 rs7222013和SLC25A2 rs3749780可能是LARC患者nCRT不良反应的潜在预测因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Human Genetics 生物-遗传学

CiteScore

4.20

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Annals of Human Genetics publishes material directly concerned with human genetics or the application of scientific principles and techniques to any aspect of human inheritance. Papers that describe work on other species that may be relevant to human genetics will also be considered. Mathematical models should include examples of application to data where possible. Authors are welcome to submit Supporting Information, such as data sets or additional figures or tables, that will not be published in the print edition of the journal, but which will be viewable via the online edition and stored on the website.