Hu Geng, Shen Shijun, Zhu Mingchao
Department of Laboratory, Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China.
Department of Hepatobiliary and Pancreatic Minimally Invasive Surgery, Lincang People's Hospital, Lincang, Yunnan 677099, P.R. China.
Mol Med Rep. 2025 Jul;32(1). doi: 10.3892/mmr.2025.13553. Epub 2025 May 9.
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.
结直肠癌(CRC)是全球第三大常见癌症,与疾病早期患者相比,其5年生存率较低,这凸显了识别早期诊断生物标志物的紧迫性。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发挥着重要作用。本研究构建了CRC中CXCL家族的预后模型,并对模型中的核心基因CXCL9进行了深入研究。CXCL9在CRC中高表达,而CRC患者中CXCL9的高表达水平通常表明预后改善。通过基因本体论、京都基因与基因组百科全书和基因集富集分析发现,CXCL9不仅与免疫调节有关,还与影响癌症发生和发展的途径密切相关。CXCL9与线粒体自噬密切相关,并通过改变自噬相关基因的表达来阻断自噬流。此外,发现CXCL9是由ALKBH5修饰的下游基因,并且可以部分恢复ALKBH5敲低诱导的肿瘤抑制作用。这些研究表明,CXCL9是CRC中的一种预后标志物,并且在癌症进展中发挥双重作用:一方面激活免疫反应,另一方面促进癌症的恶性特征。