CDCA2 triggers in vivo and in vitro proliferation of hepatocellular carcinoma by activating the AKT/CCND1 signaling.

PURPOSE: This study aims to elucidate the biological functions of CDCA2 (cell division cycle associated 2) in hepatocellular carcinoma (HCC) progression and the potential mechanism. METHODS: CDCA2 levels in HCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between CDCA2 and clinical characteristics in HCC patients was analyzed. Cox proportional-hazards model was applied for assessing the potential factors influencing overall survival in HCC. Three CDCA2 siRNAs were generated and the most effective one was used in the following experiments. After knockdown of CDCA2 in HCC-LM3 cells, clonality and viability were examined. Meanwhile, cell cycle progression was detected by flow cytometry. Relative levels of CDCA2, p21, p27, CDK2, CCND1, CCNE1 and CCNB1 in HCC-LM3 cells were determined by qRT-PCR. The activation of the protein kinase B (Akt) signaling was examined by Western blot. Subsequently, we constructed HCC xenograft model in nude mice. Tumor volume and tumor weight of xenografted HCC were recorded. RESULTS: CDCA2 was upregulated in HCC tissues than that of para-tumor ones, especially HCC tissues with larger than 5 cm in tumor size or vascular invasion. CDCA2 level was related to tumor size, vascular invasion and tumor differentiation in HCC. Knockdown of CDCA2 inhibited clonality and viability in HCC-LM3 cells, and arrested cell cycle progression in G1 phase via downregulating CCND1. The phosphatidilinositol 3-kinase (PI3K)/Akt was activated by CDCA2 during the progression of HCC. Tumor volume and tumor weight of xenografted HCC decreased in nude mice with in vivo knockdown of CDCA2. CONCLUSIONS: CDCA2 triggers proliferative potential in HCC by targeting CCND1 via activating the PI3K/Akt signaling.

The value of combined detection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the differential diagnosis of lung cancer.

BACKGROUND: To investigate the value of carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC-Ag), and gastrin-releasing peptide (pro-GRP) in the differential diagnosis of lung cancer. METHODS: We enrolled 120 patients with malignant lung cancer who were treated at our hospital between June 2018 to June 2020. A further 58 patients with benign lung tumors and 60 healthy volunteers were also enrolled. Serum levels of CEA, CYFRA21-1, SCC-Ag, and pro-GRP were determined and compared across different populations, different pathological types, and different TNM stages. An ROC curve was drawn to evaluate the value of the four indicators when combined for the diagnosis of lung cancer. RESULTS: The levels of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the malignant group were significantly higher than those in the benign and healthy groups (P<0.05). CEA in adenocarcinoma was significantly higher than that in squamous cell carcinoma (SCC) and small cell carcinoma (P>0.05), and CYFRA21-1 in non-small cell carcinoma was significantly higher than that in small cell carcinoma (P<0.05). Pro-GRP in small cell carcinoma was significantly higher than that in non-small cell carcinoma (P<0.05), and the SCC-Ag level in SCC was significantly higher than that in small cell carcinoma and adenocarcinoma (P<0.05). There was no statistically significant difference in CEA among various pathological types (P>0.05). However, there were significant differences in the levels of CEA and pro-GRP in different TMN stages (P<0.05), and in the levels of CEA and pro-GRP in different TMN stages (P<0.05) where from stage I to stage IV CEA, pro -GRP levels increased. There was a significant difference in CYFRA21-1 levels in stages I-III (P<0.05), and in stages III and IV, although there was no statistically significant difference in SCC-Ag in different stages (P>0.05). The area under the curve (AUC) for the combined diagnosis of lung cancer with the four markers was 0.9250 (95% CI: 0.8866-0.9634), the sensitivity was 93.29%, and the specificity was 84.32%. CONCLUSIONS: Joint inspection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP levels has certain clinical value for the differential diagnosis of lung cancer.