Dataset Information

Solute carrier family 2 members 1 and 2 as prognostic biomarkers in hepatocellular carcinoma associated with immune infiltration.

ABSTRACT:

Background

Metabolic reprogramming has been identified as a core hallmark of cancer. Solute carrier family 2 is a major glucose carrier family. It consists of 14 members, and we mainly study solute carrier family 2 member 1 (SLC2A1) and solute carrier family 2 member 2 (SLC2A2) here. SLC2A1, mainly existing in human erythrocytes, brain endothelial cells, and normal placenta, was found to be increased in hepatocellular carcinoma (HCC), while SLC2A2, the major transporter of the normal liver, was decreased in HCC.

Aim

To identify if SLC2A1 and SLC2A2 were associated with immune infiltration in addition to participating in the metabolic reprogramming in HCC.

Methods

The expression levels of SLC2A1 and SLC2A2 were tested in HepG2 cells, HepG215 cells, and multiple databases. The clinical characteristics and survival data of SLC2A1 and SLC2A2 were examined by multiple databases. The correlation between SLC2A1 and SLC2A2 was analyzed by multiple databases. The functions and pathways in which SLC2A1, SLC2A2, and frequently altered neighbor genes were involved were discussed in String. Immune infiltration levels and immune marker genes associated with SLC2A1 and SLC2A2 were discussed from multiple databases.

Results

The expression level of SLC2A1 was up-regulated, but the expression level of SLC2A2 was down-regulated in HepG2 cells, HepG215 cells, and liver cancer patients. The expression levels of SLC2A1 and SLC2A2 were related to tumor volume, grade, and stage in HCC. Interestingly, the expression levels of SLC2A1 and SLC2A2 were negatively correlated. Further, high SLC2A1 expression and low SLC2A2 expression were linked to poor overall survival and relapse-free survival. SLC2A1, SLC2A2, and frequently altered neighbor genes played a major role in the occurrence and development of tumors. Notably, SLC2A1 was positively correlated with tumor immune infiltration, while SLC2A2 was negatively correlated with tumor immune infiltration. Particularly, SLC2A2 methylation was positively correlated with lymphocytes.

Conclusion

SLC2A1 and SLC2A2 are independent therapeutic targets for HCC, and they are quintessential marker molecules for predicting and regulating the number and status of immune cells in HCC.

SUBMITTER: Peng Q

PROVIDER: S-EPMC9131213 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Solute carrier family 2 members 1 and 2 as prognostic biomarkers in hepatocellular carcinoma associated with immune infiltration.

Peng Qing Q Hao Li-Yuan LY Guo Ying-Lin YL Zhang Zhi-Qin ZQ Ji Jing-Min JM Xue Yu Y Liu Yi-Wei YW Lu Jun-Lan JL Li Cai-Ge CG Shi Xin-Li XL

World journal of clinical cases 20220501 13

<h4>Background</h4>Metabolic reprogramming has been identified as a core hallmark of cancer. Solute carrier family 2 is a major glucose carrier family. It consists of 14 members, and we mainly study solute carrier family 2 member 1 (SLC2A1) and solute carrier family 2 member 2 (SLC2A2) here. SLC2A1, mainly existing in human erythrocytes, brain endothelial cells, and normal placenta, was found to be increased in hepatocellular carcinoma (HCC), while SLC2A2, the major transporter of the normal liv ...[more]

PMID: 35665115

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Project description:Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies. It is not easy to be diagnosed in the early stage and is prone to relapse, with a very poor prognosis. And immune cell infiltration and tumor microenvironment play important roles in predicting therapeutic response and prognosis of HCC. Machado-Joseph domain-containing proteases (MJDs), as a gene family extensively involved in tumor progression, has pro-cancer and anti-cancer effects. However, the relationship between MJDs family members and immune cell infiltration and tumor microenvironment in HCC remains unclear. Therefore, cBio Cancer Genomics Portal (cBioPortal), The Cancer Genome Atlas (TCGA), UALCAN, Human Protein Atlas (HPA), MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were performed to investigate the mRNA expression, DNA methylation, clinicopathologic features, immune cell infiltration and other related functions of MJDs family members in HCC. The results indicated that the expression of ATXN3, JOSD1, and JOSD2 was dramatically increased in HCC tissues and cell lines, and was correlated with histological grade, specimen type, TP53 mutation, lymph node metastatic, gender, and age of patients with HCC. Meanwhile, these genes also showed clinical value in improving the overall survival (OS), disease-specific survival (DSS), progression free survival (PFS), and relapse-free survival (RFS) in patients with HCC. The prognostic model indicated that the worse survival was associated with overall high expression of MJDs members. Next, the results suggested that promotor methylation levels of the MJDs family were closely related to these family mRNA expression levels, clinicopathologic features, and prognostic values in HCC. Moreover, the MJDs family were significantly correlated with CD4+ T cells, CD8+ T cells, B cells, neutrophils, macrophages, and DCs. And MJDs family members' expression were substantially associated with the levels of several lymphocytes, immunomoinhibitors, immunomostimulators, chemokine ligands, and chemokine receptors. In addition, the expression levels of MJDs family were significantly correlated with cancer-related signaling pathways. Taken together, our results indicated that the aberrant expression of MJDs family in HCC played a critical role in clinical feature, prognosis, tumor microenvironment, immune-related molecules, mutation, gene copy number, and promoter methylation level. And MJDs family may be effective immunotherapeutic targets for patients with HCC and have the potential to be prognostic biomarkers.

Project description:Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality rates. The inhibitors of apoptosis (IAP) family act as oncogenes in various tumor types; however, their functions in HCC remain unclear. Here, we used integrated bioinformatics analysis and experimental verification to assess the expression and the prognostic and clinical value of the IAP family in HCC. Using the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) and the Tumor Immune Estimation Resource (TIMER), we analyzed the expression profiles of IAP family members in HCC tissue, normal tissues, and in patients with different stages and grades of HCC. We further verified the expression level of BIRC2 in 25 HCC samples and matched adjacent normal tissues using quantitative real-time PCR (qRT-PCR), and analyzed its correlation with the marker gene of T-helper type 1 cells (Th1)-STAT1. Meanwhile, the association between BIRC2 and the immunotherapeutic response or immunomodulators was confirmed using the Biomarker Exploration of Solid Tumors (BEST) database. The results showed that NAIP, BIRC2, BIRC3, XIAP, BIRC5, and BIRC6 mRNAs were overexpressed in HCC. The clinical stages, pathological grades, and other clinicopathological features of HCC were closely related to the expression levels of the IAP family members, especially the BIRC2 and BIRC5, which were found to be potential prognostic biomarkers for HCC. Expression of the IAPs was strongly associated with immune cell infiltration. Based on the infiltrative status of various immune cells, HCC patients with high BIRC2 and BIRC5 expression demonstrated poor overall survival (OS) rates. In patients with HCC, BIRC2 expression was noticeably elevated. Concurrently, the expression levels of BIRC2 and STAT1 showed a favorable correlation. BEST database analysis revealed that BIRC2 was a negative predictor of responsiveness to anti-programmed cell death ligand 1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitor treatment in HCC, and BIRC2 mRNA expression levels were positively correlated with the expression levels of the immune checkpoint genes programmed cell death protein 1 (PD-1), PD-L1, and CTLA-4 in HCC. Consequently, the IAP family may play a role in carcinogenesis and cancer-immune system interactions in HCC. Our results demonstrate that IAP family members may be viable predictive biomarkers and therapeutic targets for HCC.

Dataset Information

Solute carrier family 2 members 1 and 2 as prognostic biomarkers in hepatocellular carcinoma associated with immune infiltration.

Background

Aim

Methods

Results

Conclusion

Publications

Solute carrier family 2 members 1 and 2 as prognostic biomarkers in hepatocellular carcinoma associated with immune infiltration.

Similar Datasets

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