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

Abstract

ObjectiveHepatocellular 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. Cell division cycle associated 2 (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.MethodsThe differentially expressed genes that were significantly upregulated in multiple RNA sequencing datasets of HCC were screened. Receiver operating characteristic (ROC) curve 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 bioinformatic analysis and in vitro experiments.ResultsThe 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 upregulation 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.ConclusionsCDCA2 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.

A pan-cancer analysis reveals the diagnostic and prognostic role of CDCA2 in low-grade glioma

“…CDCA2 promotes the pathogenesis of HCC by inhibiting the p53-PUMA/NOXA signaling pathway. And overexpression of CDCA2 is related to poor stage, pathological grade, and clinical outcome [ 18 ].…”

Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma

“…The bisulphite-converted methylated sequence (Bs-M) and bisulphite-converted unmethylated sequence (Bs-UM) corresponding to the differential methylation regions of GNB4, and Riplet and ACTB genes were constructed on vector pUC57 (Wuhan GeneCreate Biological Engineering Co., Ltd. Wuhan, China). The constructed plasmids were serially diluted to 10 [ 3 ], 200, 40 copies/μl, and 8 copies/μl.…”

“…First, the amplification efficiency of the primers should be between 90.0% and 110.0%. The standard curves included 8 copies/μl to 10 [ 3 ] copies/μl of Bs-M of GNB4 plasmids for GNB4 primers and 8 copies/μl to 10 [ 3 ] copies/μl of Bs-M of Riplet plasmids for Riplet primers. Second, the primers and probes should only amplify the methylated templates tested in the methylated cell line (HepG2) and non-methylated cell line (A549) (Supplemental Figure S1, Supplemental Figure S2).…”

“…As a high-risk country for HCC, new cases of HCC in China account for 45.3% of all new HCC cases worldwide in 2022 [ 2 ]. The high-risk population for HCC mainly includes those with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, excessive alcohol consumption, non-alcoholic fatty liver disease (NAFLD), cirrhosis caused by other reasons, and a family history of HCC [ 3 , 4 ]. Liver cirrhosis is the most critical factor in the development of HCC, with approximately 80–90% of HCC cases arising in the setting of background cirrhosis [ 5 ].…”

“…The quality of ultrasound imaging results can also be affected by patients, such as obese patients or NAFLD patients, which can lead to an increase in false positives or indeterminate results [ 13 , 14 ]. While serum AFP is the most cost-effective biomarker for HCC screening, its sensitivity is suboptimal, with up to 40% of HCC patients testing AFP-negative [ 3 ]. To overcome the limitations of both ultrasound and AFP, high-performance biomarkers need to be developed.…”