AUTHOR=Yu Zhenjun , Zhang Yu , Shao Shuai , Liu Qi , Li Yuhan , Du Xiaoxiao , Zhang Kun , Zhang Mengxia , Yuan Haixia , Yuan Qiang , Liu Tong , Gao Yingtang , Wang Yijun , Hong Wei , Han Tao 

TITLE=Identification of CDCA2 as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.755814

DOI=10.3389/fonc.2021.755814

ISSN=2234-943X

ABSTRACT=Objective: Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors with an insidious onset, difficult early diagnosis and limited therapy options, resulting in a poor prognosis. CDCA2, also known as Repo-Man, plays an important role in regulating mitosis and DNA repair, but the involvement of CDCA2 in HCC remains unclear.
Methods: The differentially expressed genes that were significantly up-regulated in multiple RNA sequencing datasets of HCC were screened. ROC analysis was performed to identify diagnostic markers for HCC. Least absolute shrinkage and selection operator COX regression analysis was performed to screen the prognosis-related genes. The screening and analyses identified CDCA2 as the target gene in this study. The expression of CDCA2 was analyzed in public databases and clinical specimens, and CDCA2 involvement in HCC was explored by both the bioinformatic analysis and in vitro experiments.
Results: The level of CDCA2 was enhanced in HCC compared with healthy livers. Overexpression of CDCA2 positively correlated with the pathological grade and TNM stage of the diseases. Furthermore, CDCA2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with CDCA2 in combination with TNM stage. Bioinformatic analysis revealed that CDCA2 was closely associated with the cell cycle, apoptosis and p53 signaling pathway. Silencing CDCA2 in Huh7 cells resulted in significant up-regulation of p53 and the downstream PUMA and NOXA, and a subsequently increased apoptosis. Inhibition of p53 signaling and apoptosis was found after overexpression of CDCA2 in L02 cells. Strikingly, the proliferation of cells was not affected by CDCA2.
Conclusions: CDCA2 was a novel diagnostic marker for HCC, and overexpression of this gene reflected poor pathological grade, stage and clinical prognosis. CDCA2 promoted the pathogenesis of HCC by suppressing the p53-PUMA/NOXA signaling and the subsequent apoptosis.