Study on the Impact of Low Expression of C4orf19 on Reshaping the Immune Microenvironment and Metabolic Pathways to Regulate Chemotherapy Sensitivity and Prognosis in Colon Adenocarcinoma

HUANG Da; WANG Xinyu; ZHENG Zhuomeng; CHEN Guoqun; DENG Xiyun

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Journal of Hunan Normal University(Medical Science) ›› 2025, Vol. 22 ›› Issue (5) : 9-18.

Study on the Impact of Low Expression of C4orf19 on Reshaping the Immune Microenvironment and Metabolic Pathways to Regulate Chemotherapy Sensitivity and Prognosis in Colon Adenocarcinoma

HUANG Da^1,2, WANG Xinyu¹, ZHENG Zhuomeng¹, CHEN Guoqun², DENG Xiyun¹

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Abstract

Objective Chromosome 4 open reading frame 19 (C4orf19) is a protein with poorly understood functions. This study aims to explore the expression, biological functions, and impact of C4orf19 on the tumor microenvironment in colon adenocarcinoma (COAD). Additionally, through drug sensitivity analysis, we aim to screen potential effective therapeutic drugs for patients with different C4orf19 expression levels, thereby providing a new theoretical and experimental basis for precision therapy of COAD. Methods The expression of C4orf19 and its impact on patient prognosis were analyzed using the TCGA-COAD dataset and the Gene Expression Omnibus (GEO) dataset. The ESTIMATE algorithm and CIBERSORT algorithm were used to assess the influence of C4orf19 expression on the tumor microenvironment in COAD patients. Immunohistochemistry was conducted to detect the expression of C4orf19 and its correlation with immune cell infiltration. GO, KEGG, and GSEA pathway enrichment analyses were performed to identify the biological processes and signaling pathways regulated by C4orf19. The relationship between C4orf19 expression and drug sensitivity in COAD patients was analyzed using the oncoPredict algorithm. Results C4orf19 expression was downregulated in COAD and associated with poor patient prognosis. Tumor microenvironment analysis revealed that the low C4orf19 expression group had decreased infiltration of resting memory CD4⁺ T cells and increased infiltration of M0 macrophages in the tumor microenvironment. Pathway enrichment analysis indicated that C4orf19 is mainly involved in regulating cytochrome P450-mediated drug metabolism and xenobiotic metabolism. Drug sensitivity analysis showed that patients with low C4orf19 expression were more sensitive to dasatinib, SN-38, and navitoclax, while patients with high C4orf19 expression were more sensitive to gemcitabine, 5-fluorouracil, pelitinib, and cetuximab. Conclusion Low C4orf19 expression promotes the formation of a suppressive tumor immune microenvironment in COAD and reduces the sensitivity of tumor cells to certain chemotherapeutic drugs.

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colon adenocarcinoma / C4orf19 / tumor microenvironment / drug sensitivity

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HUANG Da, WANG Xinyu, ZHENG Zhuomeng, CHEN Guoqun, DENG Xiyun. Study on the Impact of Low Expression of C4orf19 on Reshaping the Immune Microenvironment and Metabolic Pathways to Regulate Chemotherapy Sensitivity and Prognosis in Colon Adenocarcinoma[J]. Journal of Hunan Normal University(Medical Science). 2025, 22(5): 9-18

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