Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 6, 2022; 10(13): 3989-4019
Published online May 6, 2022. doi: 10.12998/wjcc.v10.i13.3989
Solute carrier family 2 members 1 and 2 as prognostic biomarkers in hepatocellular carcinoma associated with immune infiltration
Qing Peng, Li-Yuan Hao, Ying-Lin Guo, Zhi-Qin Zhang, Jing-Min Ji, Yu Xue, Yi-Wei Liu, Jun-Lan Lu, Cai-Ge Li, Xin-Li Shi
Qing Peng, Li-Yuan Hao, Ying-Lin Guo, Zhi-Qin Zhang, Jing-Min Ji, Yu Xue, Yi-Wei Liu, Jun-Lan Lu, Cai-Ge Li, Xin-Li Shi, Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China
Author contributions: Shi XL and Peng Q designed this research and wrote the main manuscript; Hao LY, Guo YL, Zhang ZQ, Ji JM, Xue Y, Liu YW, Lu JL, and Li CG contributed to the analysis and wrote the manuscript in detail; All authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81873112; Natural Science Foundation of Hebei Province, No. H2020423009; Hundred Outstanding Innovative Talents Support Program of Universities in Hebei Province, No. SLRC2019043; Basic Scientific Research Project of Hebei Provincial Colleges and Universities, No. JTZ2020005; and Scientific and Technological Capability Improvement Project of the Hebei University of Chinese Medicine, No. KTZ2019002.
Conflict-of-interest statement: The authors declare no competing interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xin-Li Shi, PhD, Professor, Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, No. 3 Xing Yuan Lu, Shijiazhuang 050200, Hebei Province, China. sxlsunshine@sina.com
Received: April 21, 2021
Peer-review started: April 21, 2021
First decision: August 8, 2021
Revised: August 17, 2021
Accepted: February 25, 2022
Article in press: February 25, 2022
Published online: May 6, 2022
Processing time: 373 Days and 17.8 Hours
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.

Keywords: Hepatocellular carcinoma; Solute carrier family 2 member 1; Solute carrier family 2 member 2; Prognostic; Immune infiltration

Core Tip: We performed an integrated bioinformatics analysis to assess the influence of solute carrier family 2 member 1 (SLC2A1) and solute carrier family 2 member 2 (SLC2A2) in hepatocellular carcinoma (HCC). This study revealed that SLC2A1 and SLC2A2 are independent therapeutic targets in HCC and that they are correlated with immune infiltration, in addition to being involved in the metabolic reprogramming in HCC.