主要促进因子超家族成员2a在肝细胞癌组织中的表达及其临床意义

The expression and clinical significance of MFSD2A in hepatocellular carcinoma

目的:探讨主要促进因子超家族成员2a(MFSD2A)在肝细胞癌组织中的表达及其与肝细胞癌临床病理指标之间的相关性,评估其对肝癌患者预后的预测价值。方法:从癌症基因组图谱(TCGA)数据库下载424例肝细胞癌和50例癌旁转录组数据以及相关临床信息。利用生物信息平台,在泛癌组织中比较MFSD2A的表达情况。使用Kaplan-Meier Plotter数据库,探索MFSD2A表达与肝癌患者预后的相关性。利用STRING数据库构建MFSD2A蛋白相互作用网络,使用GEPIA2数据库检索相关基因,进一步进行通路富集分析,探索MFSD2A的分子功能。采用免疫组织化学验证肝细胞癌肿瘤组织中MFSD2A蛋白的表达情况。结果:TCGA数据分析显示,MFSD2A基因在不同肿瘤和癌旁组织中表达水平普遍存在差异,与癌旁组织相比,在肝细胞癌组织中低表达(P<0.01)。MFSD2A在>60岁组(P=0.014)、病理分级G1组(P<0.01)、血液中AFP含量≤400 ng/mL组(P<0.01)表达量升高。MFSD2A高表达组肿瘤患者的总生存期(P=0.008)、无进展生存期(P=0.008)和无复发生存期(P=0.016)均显著延长。MFSD2A及其相互作用蛋白主要涉及脂质代谢相关的PPAR信号通路。免疫组织化学验证结果显示,相对于MFSD2A低表达组患者,MFSD2A高表达组患者预后更好(P=0.016),且随着患者MFSD2A评分升高,血清AFP水平下降。结论:MFSD2A在肝细胞癌组织中低表达,且与患者不良预后相关。MFSD2A可能通过调控肝脏脂质代谢抑制肝细胞癌的进展,提示其可能是肝细胞癌的潜在治疗靶点。

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.