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溶质载体家族2成员1和2作为与免疫浸润相关的肝细胞癌的预后生物标志物。

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

作者信息

Peng Qing, Hao Li-Yuan, Guo Ying-Lin, Zhang Zhi-Qin, Ji Jing-Min, Xue Yu, Liu Yi-Wei, Lu Jun-Lan, Li Cai-Ge, Shi Xin-Li

机构信息

Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China.

出版信息

World J Clin Cases. 2022 May 6;10(13):3989-4019. doi: 10.12998/wjcc.v10.i13.3989.

DOI:10.12998/wjcc.v10.i13.3989
PMID:35665115
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9131213/
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.

摘要

背景

代谢重编程已被确定为癌症的一个核心特征。溶质载体家族2是主要的葡萄糖载体家族。它由14个成员组成,我们在此主要研究溶质载体家族2成员1(SLC2A1)和溶质载体家族2成员2(SLC2A2)。SLC2A1主要存在于人类红细胞、脑内皮细胞和正常胎盘中,在肝细胞癌(HCC)中发现其表达增加,而正常肝脏中的主要转运体SLC2A2在HCC中表达降低。

目的

确定SLC2A1和SLC2A2除了参与HCC的代谢重编程外,是否还与免疫浸润相关。

方法

在HepG2细胞、HepG215细胞和多个数据库中检测SLC2A1和SLC2A2的表达水平。通过多个数据库检查SLC2A1和SLC2A2的临床特征和生存数据。通过多个数据库分析SLC2A1和SLC2A2之间的相关性。在String中讨论SLC2A1、SLC2A2以及经常发生改变的邻近基因所涉及的功能和途径。从多个数据库讨论与SLC2A1和SLC2A2相关的免疫浸润水平和免疫标记基因。

结果

在HepG2细胞、HepG215细胞和肝癌患者中,SLC2A1的表达水平上调,但SLC2A2的表达水平下调。SLC2A1和SLC2A2的表达水平与HCC中的肿瘤体积、分级和分期相关。有趣的是,SLC2A1和SLC2A2的表达水平呈负相关。此外,高SLC2A1表达和低SLC2A2表达与较差的总生存期和无复发生存期相关。SLC2A1、SLC2A2以及经常发生改变的邻近基因在肿瘤的发生和发展中起主要作用。值得注意的是,SLC2A1与肿瘤免疫浸润呈正相关,而SLC2A2与肿瘤免疫浸润呈负相关。特别是,SLC2A2甲基化与淋巴细胞呈正相关。

结论

SLC2A1和SLC2A2是HCC的独立治疗靶点,它们是预测和调节HCC中免疫细胞数量和状态的典型标记分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8863/9131213/5b3af95f2aa7/WJCC-10-3989-g009.jpg
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