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新型生物标志物FATP5在结直肠癌中的过表达及预后意义

Over-Expression and Prognostic Significance of FATP5, as a New Biomarker, in Colorectal Carcinoma.

作者信息

Geng Qi-Shun, Yang Mei-Jia, Li Li-Feng, Shen Zhi-Bo, Wang Long-Hao, Zheng Yuan-Yuan, Xue Wen-Hua, Zhao Jie

机构信息

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Internet Medical and System Applications of National Engineering Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Mol Biosci. 2022 Jan 27;8:770624. doi: 10.3389/fmolb.2021.770624. eCollection 2021.

Abstract

Fatty acid transporters (FATPs) family play an important role in the uptake and metabolism regulation of long-chain fatty acids, which influence the occurrence and developing of multiple tumors. Fatty acid transporter 5(FATP5), a member of FATPs family, participates in fatty acid transport and lipid metabolism and is related to tumor development, whose mechanism in colorectal cancer (CRC) remains unclear. In this study, we comprehensively utilized a range of relevant bioinformatic tools along with multiple databases to analyze the expression of FATPs family and investigate the biological function and prognostic value of FATP5 in CRC. Besides, cell proliferation and cell cycle distribution analysis, western blotting and immunohistochemistry (IHC) further validated the conclusion of bioinformatics analysis. FATP5 is the only member of FATPs family which was overexpressed in CRC. In the survival analysis based on the GSE39582 databases, the low expression of FATP5 predicts poor prognosis in CRC. Similar results were also observed in GSE17536, GSE28814 and TCGA colon cohorts. The potential function of DNA methylation regulated the abnormal expression of FATP5 in CRC. In addition, enrichment analysis indicated that FATP5 also participates in the regulation of cell cycle. Furthermore, Gene Set Enrichment Analysis (GSEA) showed a strong negative correlation between FATP5 and cell growth, implying that it may participate in regulating cancer cell proliferation by the regulation of cell cycle G2/M transition. At last, we identified that FATP5 was overexpressed in colorectal carcinoma tissues through immunohistochemistry staining, and played an important role in cell cycle by cell proliferation and cell cycle distribution analysis. This study suggested that FATP5 was overexpression in colorectal carcinoma and predicted favorable prognosis, indicating it as a novel appealing prognostic marker for CRC.

摘要

脂肪酸转运蛋白(FATPs)家族在长链脂肪酸的摄取和代谢调节中发挥着重要作用,这会影响多种肿瘤的发生和发展。脂肪酸转运蛋白5(FATP5)是FATPs家族的成员之一,参与脂肪酸转运和脂质代谢,与肿瘤发展相关,其在结直肠癌(CRC)中的作用机制尚不清楚。在本研究中,我们综合利用了一系列相关生物信息学工具以及多个数据库来分析FATPs家族的表达,并研究FATP5在CRC中的生物学功能和预后价值。此外,细胞增殖和细胞周期分布分析、蛋白质免疫印迹法和免疫组织化学(IHC)进一步验证了生物信息学分析的结论。FATP5是FATPs家族中唯一在CRC中过表达的成员。在基于GSE39582数据库的生存分析中,FATP5的低表达预示着CRC的预后不良。在GSE17536、GSE28814和TCGA结肠队列中也观察到了类似结果。DNA甲基化的潜在功能调节了CRC中FATP5的异常表达。此外,富集分析表明FATP5也参与细胞周期的调节。此外,基因集富集分析(GSEA)显示FATP5与细胞生长之间存在强烈的负相关,这意味着它可能通过调节细胞周期G2/M期转换来参与调节癌细胞增殖。最后,我们通过免疫组织化学染色确定FATP5在结直肠癌组织中过表达,并通过细胞增殖和细胞周期分布分析在细胞周期中发挥重要作用。本研究表明,FATP5在结直肠癌中过表达并预示着良好的预后,表明它是一种新型且有吸引力的CRC预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ce/8829069/2a635222c7ea/fmolb-08-770624-g001.jpg

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