Department of General Surgery, Siping Central People's Hospital, Siping, Jilin, China.
Department of Surgery, Chinese Medical Sciences University, Shenyang, Liaoning, China.
Int J Immunopathol Pharmacol. 2024 Jan-Dec;38:3946320241286565. doi: 10.1177/03946320241286565.
We aimed to explore the role of structural maintenance of chromosomes 4 (SMC4) in malignant progression and immunology of colon adenocarcinoma (COAD).
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.
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.
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.
我们旨在探索染色体结构维持蛋白 4（SMC4）在结肠腺癌（COAD）恶性进展和免疫学中的作用。
通过公共数据库和网站提供 SMC4 在泛癌症中的表达、遗传和蛋白质特征以及免疫细胞浸润情况。免疫组织化学检测 COAD 组织中 SMC4 的蛋白表达。在 COAD 细胞中进行 Si-RNA 介导的转染，并通过 MTT、集落形成和 EdU 测定测量细胞增殖活力。通过 AO 染色、western blot 和免疫荧光染色检测细胞自噬。通过划痕和 Transwell 测定测定迁移能力。通过 western blot 检测上皮间质转化（EMT）标志物和转录因子的表达。
SMC4 在泛癌症中表达上调，与癌症患者的预后、TMB 和 MSI 相关。特别是，SMC4 蛋白在 COAD 组织中高表达，与患者的不良预后相关。SMC4 耗竭通过 EMT 进展抑制 COAD 细胞的增殖、诱导自噬并降低迁移能力。此外，SMC4 与 COAD 中的中性粒细胞、M2 巨噬细胞和 CD4+T 细胞浸润有关，并与 M2 巨噬细胞标志物和免疫检查点呈正相关。
SMC4 与患者的不良预后、增殖、转移和免疫细胞浸润有关，可能是 COAD 的潜在诊断和预后生物标志物。
