Prognostic implications of cell division cycle protein 45 expression in hepatocellular carcinoma

Chen Yang; Shufang Xie; Yi Wu; Guoqing Ru; Xianglei He; Hong-Yin Pan; Shibing Wang; Xiangmin Tong

doi:10.7717/peerj.10824

Prognostic implications of cell division cycle protein 45 expression in hepatocellular carcinoma

PeerJ. 2021 Feb 12:9:e10824. doi: 10.7717/peerj.10824. eCollection 2021.

Authors

Chen Yang^#^{1

2}, Shufang Xie^#^{2

3}, Yi Wu⁴, Guoqing Ru⁵, Xianglei He⁵, Hong-Yin Pan⁶, Shibing Wang^{2

7}, Xiangmin Tong^{2

7}

Affiliations

¹ Department of Clinical Medicine, Qingdao University, Qingdao, China.
² Molecular Diagnosis Laboratory, Zhejiang Provincial People's Hospital, Hangzhou, China.
³ The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
⁴ Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, Hangzhou, China.
⁵ Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, China.
⁶ Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Hangzhou, China.
⁷ The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, China.

^# Contributed equally.

Abstract

Background: The overall prognosis of hepatocellular carcinoma (HCC) is poor and novel prognostic biomarkers might better monitor the progression of HCC. Cell division cycle protein 45 (CDC45) plays a key role in DNA replication and considered to be involved in tumorigenesis. This study investigated CDC45 expression in tumour tissues and defined its prognostic value in HCC patients.

Methods: We used immunohistochemistry (IHC) staining to examine the expression of CDC45 in tumour tissue specimens and compare them with adjacent normal tissue specimens using a constructed tissue microarray (TMA) and analyzed how clinical features are related to HCC prognosis. Functional enrichment analyses were used to describe significantly involved hallmark pathways of differentially expressed genes (DEGs, which were screened out according to the high or low expression of CDC45 in tumour tissues).

Results: Our findings showed that the proteome expression of CDC45 was evidently downregulated in HCC tissues compared with matched normal tissues (P < 0.0001). Although we did not find any differences in terms of vascular invasion, metastasis, lymphatic infiltration, or Edmondson grade between patients with high and low CDC45 expression, low CDC45 expression was significantly correlated with microvascular invasion (P = 0.046). Multivariate analysis indicated that CDC45 expression (P = 0.035) was an independent prognostic factor for the overall survival (OS) rate of HCC patients. Patients with CDC45 expression was positively correlated with OS rates among HCC patients (P < 0.05). Functional annotations indicated that CDC45 is involved in the most significant pathways, including the cell cycle, DNA replication, chemical carcinogenesis and drug metabolism-cytochrome P450 pathways.

Discussion: Our findings showed that low proteomic level of CDC45 was associated with a poor prognosis in HCC patients, indicating that CDC45 might be a novel prognostic marker.

Keywords: Bioinformatics; Biomarker; Cell division cycle protein 45; Hepatocellular carcinoma.

Grants and funding

This study was supported by the Zhejiang Medical Technology Plan Project (No. WKJ-ZJ-1709, 2020KY052) and the Zhejiang Provincial Natural Science Foundation of China (No. LY19H160037, LGF18H160025, LY17H160062, 2017C33116). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.