SMC4 serves as a potential marker for the diagnosis and prognosis of colon adenocarcinoma.

Objective: We aimed to explore the role of structural maintenance of chromosomes 4 (SMC4) in malignant progression and immunology of colon adenocarcinoma (COAD).

Methods: The expression, genetic and protein features, and immune cell infiltration of SMC4 in pan-cancer were provided by public databases and websites. The protein expression of SMC4 in COAD tissues was screened by immunohistochemical assay. Si-RNA-mediated transfection was performed in COAD cells and the proliferation viability was measured using MTT, colony formation and EdU assays. Cell autophagy was detected by AO staining, western blots, and immunofluorescence staining. The migratory ability was determined using scratch and transwell assays. The expression of epithelial-to-mesenchymal transition (EMT) markers and transcriptional factors were detected using western blots.

Results: The expression of SMC4 was upregulated in pan-cancer and had relationships with prognosis, TMB, and MSI of cancer patients. Particularly, SMC4 protein was highly expressed in COAD tissues and correlated with poor prognosis of patients. Depletion of SMC4 inhibited cell proliferation, induced autophagy, and decreased migration through EMT progression in COAD cells. In addition, SMC4 was associated with infiltration of neutrophils, M2 macrophages, and CD4 + T cells in COAD, and had positive association with M2 macrophage markers and immune checkpoints.

Conclusion: SMC4 was correlated with patients' poor prognosis, proliferation, metastasis, and immune cell infiltrates, and might function as a potential diagnosis and prognostic biomarker in COAD.