Coiled-coil domain-containing protein 58 (CCDC58) is a novel prognostic biomarker correlated with mitochondrial functions in hepatocellular carcinoma

Ling Chen; Jiaxin Zhang; Yulong Yang; Jin Shu; Jianming Zheng; Xianbao Zhan; Meng Guo

Coiled-coil domain-containing protein 58 (CCDC58) is a novel prognostic biomarker correlated with mitochondrial functions in hepatocellular carcinoma

Am J Transl Res. 2023 Apr 15;15(4):2568-2584. eCollection 2023.

Authors

Ling Chen¹, Jiaxin Zhang², Yulong Yang³, Jin Shu², Jianming Zheng³, Xianbao Zhan¹, Meng Guo⁴

Affiliations

¹ Department of Oncology, Changhai Hospital, Naval Medical University Shanghai 200433, The People's Republic of China.
² Department of Gerontology, Jing'an District Shibei Hospital Shanghai 200433, The People's Republic of China.
³ Department of Pathology, Changhai Hospital, Naval Medical University Shanghai 200433, The People's Republic of China.
⁴ National Key Laboratory of Medical Immunology, Institute of Immunology, Naval Medical University Shanghai 200433, The People's Republic of China.

PMID: 37193151
PMCID: PMC10182519

Abstract

Background: Recent researches found that mitochondrial functions were substantially involved in tumor progression, whereas the particular mechanism is unrecognized. Coiled-Coil Domain-Containing Protein 58 (CCDC58), one of the mitochondrial matrix import factors, acts as a novel regulator or stabilizer involved in mitochondrial protein import machinery. Whether and how an up-regulation of CCDC58 causes poor prognosis of patients in Hepatocellular Carcinoma (HCC) still required further researches.

Methods: Tumor immune estimation resource (TIMER), Hepatocellular Carcinoma Database (HCCDB) and UALCAN databases were utilized to explore the expression level in diverse types of tumors compared with normal tissues. The prognostic potential of CCDC58 mRNA was evaluated via the Kaplan-Meier plotter, Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas (HPA) databases. Corresponding clinicopathological factors were analyzed in Kaplan-Meier plotter. According to the median of mRNA expression levels of CCDC58, we divided The Cancer Genome Atlas (TCGA) data of HCC patients into two groups, highly expressed one and lowly expressed one, so as to perform the enrichment analyses of Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Protein-Protein Interaction (PPI) Network was constructed by STRING site and the co-expressed genes were functionally enriched. Immunohistochemistry was adopted to detect protein expression of CCDC58 in HCC patients.

Results: This study indicated that CCDC58 protein expression level was obviously higher in HCC than that in paired paracancerous tissues. The up-regulated CCDC58 mRNA is prone to poor prognosis of patients in HCC through various indexes, such as overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), relapse-free survival (RFS) and progression-free survival (PFS). Additionally, univariate and multivariate Cox regression analyses suggested that CCDC58 could be viewed as an independent risk factor for HCC patients. The expression of CCDC58 is associated with 28 GO terms related to mitochondria and 5 KEGG pathways including oxidative phosphorylation. The PPI network revealed 10 interactive proteins about constituent components of mitochondria.

Conclusions: These findings demonstrated CCDC58 to be a potential diagnostic and prognostic biomarker in HCC and correlated with mitochondria acting on tumor biosynthesis and energy production. It is reliable for CCDC58 to be targeted to design novel treatments for HCC patients.

Keywords: Coiled-coil domain-containing protein 58; hepatic cell carcinoma; mitochondria; prognosis.