Dataset Information

Clinical Significance and Integrative Analysis of the SMC Family in Hepatocellular Carcinoma.

ABSTRACT: Worldwide, hepatocellular carcinoma (HCC) is one of the most malignant cancers with poor prognosis. The structural maintenance of chromosomes (SMC) gene family has been shown to play important roles in human cancers. Nevertheless, the role of SMC members in HCC is not well-understood. In this study, we comprehensively explored the role of the SMC family in HCC using a series of bioinformatic analysis tools. Studies have demonstrated that the mRNA expression levels of SMC1A, SMC1B, SMC2, SMC4, and SMC6 are significantly overexpressed in HCC, and the protein levels of SMC1A, SMC2, SMC3, SMC4, SMC5, and SMC6 are similarly elevated. Moreover, HCC patients with high SMC2 and SMC4 expression levels exhibit poor survival. Using KEGG and GO analyses, we analyzed the enrichment of gene expression in the biological functions and pathways of the SMC family in HCC. Immune infiltration analysis revealed that the expression of the SMC family is closely associated with B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and DCs. In conclusion, our findings will enhance a more thorough understanding of the SMC family in HCC progression and provide new directions for the diagnosis and treatment of HCC in the future.

SUBMITTER: Nie H

PROVIDER: S-EPMC8437102 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical Significance and Integrative Analysis of the SMC Family in Hepatocellular Carcinoma.

Nie Hui H Wang Yutong Y Yang Xuejie X Liao Zhiming Z He Xiaoyun X Zhou Jianhua J Ou Chunlin C

Frontiers in medicine 20210830

Worldwide, hepatocellular carcinoma (HCC) is one of the most malignant cancers with poor prognosis. The structural maintenance of chromosomes (SMC) gene family has been shown to play important roles in human cancers. Nevertheless, the role of SMC members in HCC is not well-understood. In this study, we comprehensively explored the role of the SMC family in HCC using a series of bioinformatic analysis tools. Studies have demonstrated that the mRNA expression levels of <i>SMC1A, SMC1B, SMC2, SMC4< ...[more]

PMID: 34527684

Similar Datasets

Project description:BACKGROUND:Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Intrahepatic metastasis, such as portal vein tumor thrombosis (PVTT), strongly indicates poor prognosis of HCC. But now, there are limited understandings of the molecular features and mechanisms of those metastatic HCCs. METHODS:To characterize the molecular alterations of the metastatic HCCs, we implemented an integrative analysis of the copy number variations (CNVs), DNA methylations and transcriptomes of matched adjacent normal, primary tumor and PVTT samples from 19 HCC patients. RESULTS:CNV analysis identified a frequently amplified focal region chr11q13.3 and a novel deletion peak chr19q13.41 containing three miRNAs. The integrative analysis with RNA-seq data suggests that CNVs and differential promoter methylations regulate distinct oncogenic processes. Then, we used individualized differential analysis to identify the differentially expressed genes between matched primary tumor and PVTT of each patient. Results show that 5 out of 19 studied patients acquire evidential progressive alterations of gene expressions (more than 1000 differentially expressed genes were identified in each patient). While, another subset of eight patients have nearly identical gene expressions between the corresponding matched primary tumor and PVTT. Twenty genes were found to be recurrently and progressively differentially expressed in multiple patients. These genes are mainly associated with focal adhesion, xenobiotics metabolism by cytochrome P450 and amino acid metabolism. For several differentially expressed genes in metabolic pathways, their expressions are significantly associated with overall survivals and vascular invasions of HCC patients. The following transwell assay experiments validate that they can regulate invasive phenotypes of HCC cells. CONCLUSIONS:The metastatic HCCs with PVTTs have significant molecular alterations comparing with adjacent normal tissues. The recurrent alteration patterns are similar to several previously published general HCC cohorts, but usually with higher severity. By an individualized differential analysis strategy, the progressively differentially expressed genes between the primary tumor and PVTT were identified for each patient. A few patients aquire evidential progressive alterations of gene expressions. And, experiments show that several recurrently differentially expressed genes can strongly regulate HCC cell invasions.

Project description:NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03-3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.

Dataset Information

Clinical Significance and Integrative Analysis of the SMC Family in Hepatocellular Carcinoma.

Publications

Clinical Significance and Integrative Analysis of the SMC Family in Hepatocellular Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets