Carcinogenesis, Teratogenesis & Mutagenesis ›› 2024, Vol. 36 ›› Issue (3): 187-194.doi: 10.3969/j.issn.1004-616x.2024.03.004

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The expression and clinical significance of MFSD2A in hepatocellular carcinoma

MA Sheng1, WANG Xijun1, LIU Zhenrong1, WANG Yaru1, HU Nan2, RONG Weiqi2, XIAO Ting1   

  1. 1. State Key Laboratory of Molecular Oncology, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021;
    2. Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
  • Received:2024-02-25 Revised:2024-03-15 Online:2024-05-30 Published:2024-06-05

Abstract: OBJECTIVE:To investigate expression of the major facilitator superfamily domain-containing protein 2a (MFSD2A) in hepatocellular carcinoma (HCC) tissues,and its correlation with clinical characteristics and prognosis of HCC patients. METHODS:The transcriptome data from 424 cases of HCC and 50 adjacent non-cancerous tissues,along with relevant clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Using a bioinformatics platform,expression of MFSD2A across various cancer types were compared. Association between MFSD2A expression and prognosis in HCC patients were evaluated using the Kaplan-Meier Plotter database. Additionally,a protein-protein interaction network of MFSD2A was constructed using the STRING database,related genes were retrieved using the GEPIA2 database,and pathway enrichment was analyzed to explore the molecular function of MFSD2A. Immunohistochemistry was performed to validate the expression of MFSD2A protein in HCC tumor tissues. RESULTS:Analysis of the TCGA data revealed significant differences in MFSD2A gene expression levels across various tissues. Specifically,MFSD2A was significantly under expressed in HCC tissues compared to adjacent tissues (P<0.01). Moreover,the expression increased in the over 60 age group (P=0.014),in the G1 pathological grade group (P<0.01),and in the group with AFP blood levels ≤400 ng/mL (P<0.01). High expression of MFSD2A was associated with significantly prolonged overall survival (P=0.008),progression-free survival (P=0.008),and recurrence-free survival (P=0.016) in patients. MFSD2A and its interacting proteins primarily participated in lipid metabolism-related PPAR signaling pathways. Immunohistochemistry analyses indicated that patients with high MFSD2A expression had better prognosis (P=0.016) compared to those with low expression,and serum AFP levels decreased with increasing MFSD2A scores. CONCLUSION:Low expression of MFSD2A was observed in HCC tissues and was associated with poor prognosis in patients. The results indicate that MFSD2A inhibited the progression of HCC by regulating hepatic lipid metabolism,and suggest that it may be a therapeutic target for hepatocellular carcinoma.

Key words: MFSD2A, hepatocellular carcinoma, prognosis, AFP, lipid metabolism

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