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

Abstract

Colorectal cancer (CRC), the third most preva‑ lent 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 iden‑ tification. 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 inves‑ tigation 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 down‑ stream 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.