Background Lung adenocarcinomas (LUAD) remain the leading cause of death in many countries. In this study, we investigated the role of division cycle‐associated 4 (CDCA4) in the carcinogenesis of LUADs. Methods Real‐time fluorescent quantitative polymerase chain reaction and western blot were performed to detect the messenger RNA and protein levels of CDCA4 in cells. Cell counting kit 8, real‐time cell analysis, clone formation, EdU assays, and cell‐cycle assays were used to preliminarily investigate the proliferation and cell‐cycle–related functions of CDCA4 in lung adenocarcinoma. Immunoprecipitation assays were used to identify possible targets of CDCA4. A xenograft model was used to examine how CDCA4 knockdown affects LUAD cells growth in vivo. Results We found that the expression of CDCA4 was upregulated in LUAD cell lines. When CDCA4 was knocked out, the ability of LUAD cells to proliferate was dramatically reduced, and the cell cycle was stalled in the S phase. Meanwhile, boosting the CDCA4 expression had the opposite effect. The critical protein levels of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway were subsequently examined. The findings demonstrated that elevated CDCA4 lowered the phosphate and tensin homolog expression and increased the p‐PI3K and p‐AKT levels. Moreover, we demonstrated that CDCA4 favorably regulated IGF2BP1, a downstream target. The downregulation of the IGF2BP1 expression could reverse the proliferation promotion effect induced by the CDCA4 overexpression. Conclusions CDCA4 can operate as an oncogenic factor to control the growth of lung adenocarcinoma via the PI3K/AKT pathway.
Background: The National Comprehensive Cancer Network (NCCN) guidelines did not give an explicit comparison of the efficacy between surgery and radiotherapy in treating Stage-III N2 non–small cell lung cancer (NSCLC) patients, leaving a paucity for clinical reference. Through this study, we try to locate the optimum treatment strategy including surgical type for these patients. Methods: A systematic literature search was performed from PubMed, Cochrane Library, Embase, and Google Scholars. The endpoints were overall survival (OS), mean OS, and progression-free survival (PFS). The treatments comprised radiotherapy, lobectomy, and pneumonectomy. Network meta-analysis was carried out for calculating the odds ratio (OR) for binary variants. All the analyses implemented Stata 17.0 MP. Results: Eight clinical trials reporting 1756 patients met the inclusion criteria. Radiotherapy and surgery were equivalent in improving patients’ OS (OR = 0.842, 95% confidence interval [CI]: [0.645, 1.099]). The mean OS of patients were similar in terms of radiotherapy, lobectomy, and pneumonectomy. Besides, radiotherapy and surgery had equivalent effects in improving PFS (OR = 0.896, 95% CI: [0.718, 1.117]). Conclusions: Since lobectomy and pneumonectomy following neoadjuvant treatments had equivalent efficacy in prolonging OS for patients with stage-IIIA N2 NSCLC compared with definitive radiotherapy, young patients with favorable performance status (0) should try surgery to pursue better prognosis while elderly patients with unfavorable PS or radiosensitive pathology types should accept definitive radiotherapy. More high-quality clinical trials are needed to support our findings.
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