CXCL9 is a dual‑role biomarker in colorectal cancer linked to mitophagy and modulated by ALKBH5.

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular medicine reports Pub Date : 2025-07-01 Epub Date: 2025-05-09 DOI:10.3892/mmr.2025.13553

Geng Hu, Shijun Shen, Mingchao Zhu

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引用次数: 0

Abstract

Colorectal cancer (CRC), the third most prevalent cancer globally, shows a diminished 5‑year survival rate compared with patients at early stages of the disease, underscoring the urgency for early diagnostic biomarker identification. The C‑X‑C motif chemokine ligand (CXCL) family plays a significant role in immune modulation and cancer progression. the present study constructed a prognostic model for CXCL family in CRC and conducted an in‑depth investigation of the hub gene CXCL9 within the model. CXCL9 is highly expressed in CRC while high expression levels of CXCL9 in patients with CRC often indicates an improved prognosis. Through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis enrichment analysis, it was discovered that CXCL9 is not only associated with immune modulation but also closely related to pathways that affect the occurrence and development of cancer. CXCL9 is closely related to mitophagy and blocks autophagy flow by altering the expression of autophagy‑related genes. Additionally, it was found that CXCL9 is a downstream gene modified by ALKBH5 and can partially restore the tumor‑suppressive effects induced by the knockdown of ALKBH5. These studies indicated that CXCL9 is a prognostic marker in CRC and plays a dual role in cancer progression: It activates immune responses on one hand and promotes the malignant characteristics of cancer on the other hand.

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CXCL9是结直肠癌中与线粒体自噬相关并受ALKBH5调节的双作用生物标志物。

结直肠癌（CRC）是全球第三大常见癌症，与处于该疾病早期阶段的患者相比，其5年生存率降低，这突显了早期诊断生物标志物鉴定的紧迫性。C - X - C基序趋化因子配体（CXCL）家族在免疫调节和癌症进展中起着重要作用。本研究构建了CXCL家族在结直肠癌中的预后模型，并对该模型中的枢纽基因CXCL9进行了深入的研究。CXCL9在结直肠癌中高表达，而CXCL9在结直肠癌患者中的高表达往往预示着预后的改善。通过基因本体、《京都基因与基因组百科全书》和基因集富集分析富集分析，发现CXCL9不仅与免疫调节有关，而且与影响癌症发生发展的通路密切相关。CXCL9与自噬密切相关，通过改变自噬相关基因的表达来阻断自噬流。此外，我们发现CXCL9是ALKBH5修饰的下游基因，可以部分恢复ALKBH5敲低诱导的肿瘤抑制作用。这些研究表明，CXCL9是结直肠癌的预后标志物，在癌症进展中起双重作用：一方面激活免疫反应，另一方面促进癌症的恶性特征。

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

Molecular medicine reports 医学-病理学

CiteScore

7.60

自引率

0.00%

发文量

321

审稿时长

1.5 months

期刊介绍： Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.