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Open Access 01-12-2023 | Hepatocellular Carcinoma | Research

Analysis of the expression and prognostic significance of DDK complex in Hepatocarcinoma

Authors: Min Wang, Zu-Hua Qiu, Yu-Zhuo Wang, Bo Lian, Jing-Kun Bai, Yong-Jie Zhou, Hong-Jie Ji

Published in: BMC Cancer | Issue 1/2023

Abstract

Background

Hepatocellular carcinoma (HCC) remains one of the most common and lethal malignancies worldwide. Although DBF4-dependent kinase (DDK) complex composed of CDC7 kinase and its regulatory subunit DBF4 has been shown to be overexpressed in primary tumors and promotes tumor development, while its role and prognostic value in HCC remain largely unknown. In the present study, the expression of DBF4 and CDC7 and their relationship with clinical characteristics were comprehensively analyzed.

Methods

The mRNA expression profiles of HCC and the corresponding clinical data of HCC patients were downloaded from TCGA and GEO databases, respectively. The differences in DBF4 and CDC7 expression in tumor tissues and adjacent normal tissues were analyzed. HCC-derived tissue microarray (TMA) was used to evaluate and score the expression of CDC7 by immunohistochemistry (IHC) staining. The Kaplan–Meier method and the Cox regression method were used to analyze the relationship between overall survival and clinical characteristics of the patients. Gene set enrichment analysis (GSEA) was used to analyze the pathway enrichment of DBF4 and CDC7.

Results

DBF4 and CDC7 had similar expression patterns in HCC patients. Detailly, compared with adjacent tissues, both mRNA and protein of DBF4 and CDC7 were significantly higher in HCC, and their expression was positively correlated with AJCC_T stage, clinical stage and G stage (grade) of liver cancer patients, and higher DBF4 or CDC7 expression predicted a worse prognosis in HCC patients with shorter overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS) and progress-free survival (PFS). Cox regression analysis suggested that both DBF4 and CDC7 were independent risk factors for the prognosis of HCC patients in TCGA dataset. GSEA suggested that both DBF4 and CDC7 were positively correlated with cell cycle and DNA replication. Finally, the prognostic value of CDC7 was furtherly confirmed by TMA-based IHC staining results.

Conclusions

Our study showed that DDK complex was significantly increased in HCC. Both DBF4 and CDC7 may be potential diagnostic and prognostic markers for HCC, and high expression of DDK members predicts a worse prognosis in patients with HCC, which may be associated with high tumor cell proliferation rate.

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Title: Analysis of the expression and prognostic significance of DDK complex in Hepatocarcinoma
Authors: Min Wang
Zu-Hua Qiu
Yu-Zhuo Wang
Bo Lian
Jing-Kun Bai
Yong-Jie Zhou
Hong-Jie Ji
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-022-10475-w

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