关键词: 细胞分裂周期蛋白20, 肺腺癌, 细胞增殖, 细胞周期, 细胞运动

Abstract:

Background and purpose: Lung adenocarcinoma has the characteristics of difficult early detection, rapid tumor progression and low surgical resection rate. Although studies on immunotherapy alone and immunotherapy combined with chemotherapy have shown initial success in improving prognosis and overcoming drug resistance, the majority of lung adenocarcinoma patients still receive limited benefits. Therefore, there is an urgent need to identify novel biomarkers with relatively high sensitivity and specificity to improve the prognosis of lung adenocarcinoma. Cell division cycle protein 20 (CDC20) is involved in the occurrence and development of various tumors, but its biological role and mechanism in lung adenocarcinoma remain unclear. The aim of this study was to investigate the expression of CDC20 in lung adenocarcinoma and its predictive value for the prognosis of patients with lung adenocarcinoma, and to further explore the effects of CDC20 on the proliferation and invasion capabilities of lung adenocarcinoma cells. Methods: Utilizing immunohistochemistry (IHC) to detect the expression of CDC20 in lung adenocarcinoma tissues, we analyzed its correlation with poor prognosis in combination with bioinformatics and clinicopathological parameters. Kaplan-Meier survival curves were employed to illustrate the impact of CDC20 on postoperative survival rates in lung adenocarcinoma patients. COX multivariate regression analysis was conducted to identify independent prognostic factors influencing postoperative survival rates. Additionally, receiver operating characteristic (ROC) curves were applied to assess the diagnostic value of CDC20 expression in lung adenocarcinoma patients. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot were used to measure the expression levels of CDC20 in normal human lung epithelial cells (BEAS-2B) and human lung adenocarcinoma cells (A549 and H1299). In cellular experiments, CDC20 was knocked down in lung adenocarcinoma cells, which were divided into three groups: si-NC (control group), si-CDC20#1 (knockdown group 1) and si-CDC20#2 (knockdown group 2). Cell counting kit-8 (CCK-8), colony formation, transwell and wound healing assays were conducted to assess cell proliferation, migration and invasion capabilities. Functional enrichment analysis using Geng Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was conducted to explore the biological roles of CDC20 in lung adenocarcinoma. Finally, gene set enrichment analysis (GSEA) was employed to investigate potential regulatory pathways of CDC20 in lung adenocarcinoma. This study was approved by the Ethics Committee of Hebei Chest Hospital (Number: 2022051). Results: The results of both bioinformatics analysis and IHC demonstrated a significantly high expression of CDC20 in lung adenocarcinoma tissues (P<0.05). Both bioinformatics analysis and clinical parameter evaluation revealed a correlation between high CDC20 expression and poor patient prognosis. Kaplan-Meier survival analysis and COX regression analysis consistently indicated a significant negative correlation between CDC20 expression and postoperative survival rates in patients (P<0.05). Additionally, the expression levels of CDC20 were higher in human lung adenocarcinoma cell lines A549 and H1299 compared with BEAS-2B (P<0.05). Knockdown of CDC20 effectively inhibited the proliferation, migration and invasion of lung adenocarcinoma cells (P<0.05). The results of GO, KEGG pathways and GSEA consistently pointed to a relationship between CDC20 and cell cycle regulation. Conclusion: CDC20 is highly expressed in lung adenocarcinoma. High expression of CDC20 is an independent risk factor for poor prognosis of lung adenocarcinoma patient. CDC20 can promote the proliferation, migration and invasion of lung adenocarcinoma cells.

Key words: Cell division cycle protein 20, Adenocarcinoma of the lung, Cell proliferation, Cell cycle, Cell movement