FUNDC1 在肝细胞癌中的预后和免疫意义：TCGA 挖掘研究。

Prognostic and Immunological Significance of FUNDC1 in Hepatocellular Carcinoma: A Study on TCGA Mining.

机构信息

Department of Oncology Medicine, Fuzhou Pulmonary Hospital of Fujian Province, The Teaching Hospital of Fujian Medical University, Fuzhou City, China.

Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, China.

出版信息

Comput Math Methods Med. 2022 Aug 16;2022:8371885. doi: 10.1155/2022/8371885. eCollection 2022.

DOI:10.1155/2022/8371885

PMID:36017155

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9398860/

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is an inflammation-related malignancy influenced by the immune microenvironment, such as immune tolerance and evasion. HFUN14 domain-with protein 1 (FUNDC1) is a necessary mitochondrial outer membrane protein, functioning as a receptor for hypoxia-caused mitophagy, which is related to human immunity. The relationship between HCC and FUNDC1 in terms of prognosis and immunology was demonstrated in the current investigation. Even so, the function of FUNDC1 in liver cancer is yet unknown.

METHODS

The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were utilized for examining if FUNDC1 expression is associated with clinicopathological characteristics and prognosis. Genetic changes (mutation), DNA methylation, and their relationship with patient prognosis were identified by cBioPortal and MethSurv. Utilizing the Tumor Immune Estimation Resource (TIMER), immune checkpoints, infiltration, and immune cell biomarkers were analyzed. Utilizing the STRING database, the network of protein-protein interactions was created. Using Gene Set Enrichment Analysis, the FUNDC1 biological roles were determined (GSEA).

RESULTS

FUNDC1 elevation was significantly linked with gender ( < 0.001), tumor stage ( = 0.01349), tumor grade ( < 0.001), and alpha-fetoprotein (AFP) ( < 0.001) levels in HCC. It was illustrated by ROC curve analysis that FUNDC1 had a significant diagnostic and prognostic value. The FUNDC1 genetic change rate was 0.6%. Four out of 6 DNA methylation CpG sites were associated with the HCC prognosis. FUNDC1 is associated strongly with immune cell infiltration in HCC. Moreover, FUNDC1 was positively related to immune checkpoints such as mutant-allele tumor heterogeneity (MATH) ( < 0.001), ploidy ( < 0.05), homologous recombination defect (HRD) ( < 0.001), and loss of heterozygosity (LOH). GSEA revealed significant FUNDC1 enrichment in the cell cycle, hedgehog, and MAPK signaling pathways.

CONCLUSION

FUNDC1 is a mitophagy regulator that could be a therapeutic, prognostic, and putative diagnostic biomarker for HCC.

摘要

背景

肝细胞癌（HCC）是一种受免疫微环境影响的炎症相关恶性肿瘤，如免疫耐受和逃逸。FUN14 结构域结合蛋白 1（FUNDC1）是一种必需的线粒体外膜蛋白，作为缺氧诱导的线粒体自噬的受体，与人类免疫有关。本研究表明 HCC 与 FUNDC1 之间在预后和免疫学方面存在关联。尽管如此，FUNDC1 在肝癌中的功能尚不清楚。

方法

利用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据集，研究 FUNDC1 表达与临床病理特征和预后的关系。利用 cBioPortal 和 MethSurv 识别遗传改变（突变）、DNA 甲基化及其与患者预后的关系。利用肿瘤免疫估计资源（TIMER）分析免疫检查点、浸润和免疫细胞生物标志物。利用 STRING 数据库构建蛋白质-蛋白质相互作用网络。通过基因集富集分析（GSEA）确定 FUNDC1 的生物学作用。

结果

FUNDC1 升高与 HCC 患者的性别（<0.001）、肿瘤分期（=0.01349）、肿瘤分级（<0.001）和甲胎蛋白（AFP）（<0.001）水平显著相关。ROC 曲线分析表明，FUNDC1 具有显著的诊断和预后价值。FUNDC1 的遗传改变率为 0.6%。6 个 DNA 甲基化 CpG 位点中的 4 个与 HCC 预后相关。FUNDC1 与 HCC 中的免疫细胞浸润密切相关。此外，FUNDC1 与免疫检查点如突变等位基因肿瘤异质性（MATH）（<0.001）、倍性（<0.05）、同源重组缺陷（HRD）（<0.001）和杂合性丢失（LOH）呈正相关。GSEA 显示 FUNDC1 在细胞周期、 hedgehog 和 MAPK 信号通路中显著富集。