Background: Lots of studies have shown that cyclin disorders can promote tumor development. This study aims to investigate the biological function and molecular mechanism of CCNB2 in lung adenocarcinoma (LUAD). Methods: LUAD data were downloaded from GEO database and TCGA-LUAD database. Differential analysis was conducted to find the differentially expressed miRNAs and mRNAs, while targeted prediction was done for the access of potential target mRNAs. Gene expression level was detected by qRT-PCR and Western blot in human LUAD cell lines A-427, A549, Calu-3, PC-9 and human bronchial epithelial cell line BEAS-2B. MTT, colony formation, Transwell and flow cytometry assays were used to detect cell proliferation, metastasis, and cell cycle changes of PC-9 cell line. The dual-luciferase reporter gene was used to detect the targeted binding relationship of the target miRNA and mRNA. Results: CCNB2 was highly expressed and served as a biomarker indicating poor prognosis in LUAD patients. Cell function experiments confirmed the inhibitory effects of silencing CCNB2 on the proliferation, migration and invasion of LUAD cells and cell cycle was blocked in the G0/G1 phase. In addition, with regard to the regulatory mechanism, we demonstrated that miR-335-5p had binding sites with 3ʹ-UTR of CCNB2, indicating that miR-335-5p could target the regulation expression of CCNB2. In subsequent cell function tests, overexpression of miR-335-5p inhibited the proliferation and metastasis of cancer cells, and the rescue experiments also verified that miR-335-5p could reverse the promotion of CCNB2 overexpression on the progress of cancer cells. Conclusion: In summary, our results revealed that miR-335-5p could target the downregulation of CCNB2 to inhibit the occurrence and development of LUAD.

PurposeTo assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC) through a trial-level meta-analysis.MethodsTrials published between 1990 and 2015 were identified by an electronic search of public databases (Medline, Embase, and Cochrane Library). All clinical studies were independently identified by two authors. Demographic data, treatment regimens, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were extracted and analyzed using comprehensive meta-analysis software (version 2.0).ResultsA total of 2,551 patients with advanced nonsquamous NSCLC from ten trials were included for analysis: 1,565 patients were treated with pemetrexed plus platinum doublet chemotherapy and 986 with platinum plus other first-line chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95% confidence interval [CI]: 31.7%–44.3%), with median PFS and OS of 5.7 and 16.05 months, respectively. When compared to other platinum-based doublet chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77–0.97, P=0.01) but not PFS (HR =0.90, 95% CI: 0.80–1.01, P=0.084) in advanced nonsquamous NSCLC patients.ConclusionPemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients. Our findings support the use of pemetrexed plus platinum doublet regimen as first-line treatment in advanced nonsquamous NSCLC patients because of its potential survival benefits.

Object. This study is aimed at evaluating the efficacy and safety of pemetrexed and gefitinib in the treatment of non-small-cell lung cancer (NSCLC). Methods. Databases, including PubMed, the Cochrane Library, Embase, CNKI, and Web of Science, were applied to search for randomized controlled trials (RCTs) about the use of pemetrexed and gefitinib in the second-line treatment of locally advanced and metastatic NSCLC from database foundation to April 2020. Meta-analysis was conducted using the RevMan 5.3 software. Primary outcomes included progression-free survival (PFS) and overall survival (OS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and all grades of drug-related adverse events (AEs). Results. Totally, 14 RCTs and 1,334 patients were involved in the study. The results of meta-analysis showed that compared with pemetrexed, gefitinib was not superior in improving ORR ( P = 0.21 ), DCR ( P = 0.52 ), PFS ( P = 0.41 ), and OS ( P = 0.79 ). Subgroup analysis showed that in patients with mutant EGFR ( P = 0.08 ) and wild-type EGFR ( P = 0.80 ), both pemetrexed and gefitinib produced a similar effect on PFS. In terms of safety, the incidence of rash ( P < 0.00001 ) and diarrhea ( P = 0.0005 ) in the gefitinib group was significantly higher than those in the pemetrexed group, while the occurrence of neutropenia ( P = 0.01 ) and fatigue ( P = 0.02 ) was significantly lower. Conclusion. Gefitinib and pemetrexed showed similar efficacy and safety, regardless of the type of EGFR. Both gefitinib and pemetrexed can be used as conventional drugs for the second-line treatment of locally advanced and metastatic NSCLC.