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. 2022 Oct 21;101(42):e31336.
doi: 10.1097/MD.0000000000031336.

Expression profile and prognostic values of SMC family members in HCC

Wei Yan  1 , Dan-Dan Wang  1 , He-Da Zhang  1 , Jinny Huang  2 , Jun-Chen Hou  1 , Su-Jin Yang  1 , Jian Zhang  1 , Ling Lu  3   4   5 , Qian Zhang  1
Affiliations

Expression profile and prognostic values of SMC family members in HCC

Wei Yan et al. Medicine (Baltimore). .

Abstract

Objective: The structural maintenance of chromosome (SMC) gene family, including 6 proteins, is involved in a wide range of biological functions in different human cancers. Nevertheless, there is little research on the expression patterns, potential functions and prognostic value of SMC genes in hepatocellular carcinoma (HCC). Based on publicly available databases and integrative bioinformatics analysis, we tried to determine the value of SMC gene expression in predicting the risk of developing HCC.

Methods: The expression and copy number variations data of SMC family members were obtained from TCGA (The Cancer Genome Atlas). We identified the prognostic values of SMC family members and their clinical features. GSEA (Gene Set Enrichment Analysis) was conducted to detect the mechanism underlying the involvement of SMC family members in liver cancer. We used Tumor Immune Estimation Resource database to explore the associations between TIICs (Tumor Immune Infiltrating Cells) and the SMC family members.

Results: Our analysis proved that downregulation of SMC family members was common modification in HCC patients. In HCC, the expression of SMC1A, SMC2, SMC3, SMC4, SMC6 were upregulated. Upregulation of SMC2, SMC3, and SMC4, along with the clinical stage of HCC, were associated with a poor prognosis according to the results of univariate and multivariate Cox proportional hazards regression analysis. SMC2, SMC3, and SMC4 are also related to tumor purity and immune infiltration levels of HCC. The GSEA results proved that SMC family members take part in numerous biological processes underlying tumorigenesis.

Conclusion: In this study, we comprehensively analyzed the expression of SMC family members in patients with HCC. This can provide insights for further investigation of the SMC members as potential therapeutic targets in HCC and suggest that the use of SMC inhibitor targeting SMC2, SMC3, and SMC4 can be a practical strategy for the therapy of HCC.

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Conflict of interest statement

The authors have no funding and conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Associations between SMC family members. SMC = structural maintenance of chromosome.
Figure 2.
Figure 2.
Expression profile of SMC members in HCC represented by a heatmap (A), histograms (B), and immunohistochemistry (C). HCC = hepatocellular carcinoma, SMC = structural maintenance of chromosome.
Figure 3.
Figure 3.
The prognostic value of mRNA Level of SMC factors in HCC patients. (A) The prognostic value of mRNA level of SMC factors in overall survival (OS) of HCC patients, (B) The prognostic value of mRNA level of SMC factors in progression-free survival (PFS) of HCC patients. HCC = hepatocellular carcinoma, SMC = structural maintenance of chromosome.
Figure 4.
Figure 4.
Forest plots of the results of multivariate Cox regression analyses of significant prognostic factors: SMC2 (A), SMC3 (B), SMC4 (C), and SMC6 (D). *P < .05; **P < .01. SMC = structural maintenance of chromosome.
Figure 5.
Figure 5.
Correlations between tumor infiltrating immune cells (TIICs; B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells) and SMC members (including SMC2, SMC3 and SMC4) in HCC. Tumor purity is shown in the panels on the left. HCC = hepatocellular carcinoma, SMC = structural maintenance of chromosome.
Figure 6.
Figure 6.
Cancer-related Kyoto encyclopedia of genes and genomes (KEGG) pathways associated with SMC2 (A), SMC3 (B), and SMC4 (C) based on a gene set enrichment analysis (GSEA). SMC = structural maintenance of chromosome.
See this image and copyright information in PMC

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