Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

作者全名："Wang, Yi-Ying; Shen, Mei-Mei; Gao, Jian"

作者地址："[Wang, Yi-Ying; Shen, Mei-Mei] Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Gao, Jian] Chongqing Med Univ, Dept Gastroenterol & Hepatol, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Gao, Jian] Chongqing Med Univ, Dept Gastroenterol & Hepatol, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Gao, J (通讯作者)，Chongqing Med Univ, Dept Gastroenterol & Hepatol, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：WORLD JOURNAL OF GASTROENTEROLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001189690400003

JCR分区：Q1

影响因子：4.3

年份：2024

卷号：30

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：Metadherin; Hepatocellular carcinoma; Cancer stem cells; Immune infiltration

摘要："BACKGROUND Metadherin (MTDH) is a key oncogene in most cancer types, including hepatocellular carcinoma (HCC). Notably, MTDH does not affect the stemness pheno-type or immune infiltration of HCC. AIM To explore the role of MTDH on stemness and immune infiltration in HCC. METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases. Immunohistochemistry was used to analyze the tissue samples. MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines. The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays. Next, we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium. Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR. Flow cytometry, immunofluorescence, and tumor sphere formation assays were used to characterize stem-like cells. The effects of MTDH inhibition on tumor growth were evaluated in vivo. The correlation of MTDH with immune cells, immunomodulators, and chemokines was analyzed using ssGSEA and TISIDB databases. RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues. High MTDH expression was associated with a poor prognosis. HCC cells overexpressing MTDH exhibited stronger invasion and migration abilities, exhibited a stem cell-like phenotype, and formed spheres; however, MTDH inhibition attenuated these effects. MTDH inhibition suppressed HCC progression and CD133 expression in vivo. MTDH was positively correlated with immature dendritic, T helper 2 cells, central memory CD8(+) T, memory B, activated dendritic, natural killer (NK) T, NK, activated CD4(+) T, and central memory CD4(+) T cells. MTDH was negatively correlated with activated CD8(+) T cells, eosinophils, activated B cells, monocytes, macrophages, and mast cells. A positive correlation was observed between the MTDH level and CXCL2 expression, whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression. CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis, promoting tumor stemness, immune infiltration, and HCC progression."

基金机构：National Natural Science Foundation of China [82173359]; Basic Research and Frontier Exploration Project of Chongqing and Technology Commission [cstc2018jcyjAX0181]; Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University

基金资助正文："Supported by National Natural Science Foundation of China, No. 82173359; Basic Research and Frontier Exploration Project of Chongqing and Technology Commission, No. cstc2018jcyjAX0181; and Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University."