Accumulating evidence has demonstrated that gene alterations play a crucial role in LUAD development, progression, and prognosis. The current study aimed to identify the hub genes associated with LUAD. In the present study, we used TCGA database to screen the hub genes. Then, we validated the results by GEO datasets. Finally, we used cBioPortal, UALCAN, qRT-PCR, HPA database, TCGA database, and Kaplan-Meier plotter database to estimate the gene mutation, gene transcription, protein expression, clinical features of hub genes in patients with LUAD. A total of 5,930 DEGs were screened out in TCGA database. Enrichment analysis revealed that DEGs were involved in the transcriptional misregulation in cancer, viral carcinogenesis, cAMP signaling pathway, calcium signaling pathway, and ECM-receptor interaction. The combining results of MCODE and CytoHubba showed that ADCY8, ADRB2, CALCA, GCG, GNGT1, and NPSR1 were hub genes. Then, we verified the above results by GSE118370, GSE136043, and GSE140797 datasets. Compared with normal lung tissues, the expression level of ADCY8 and ADRB2 were lower in LUAD tissues, but the expression level of CALCA, GCG, GNGT1, and NPSR1 were higher. In the prognosis analyses, the low expression of ADCY8 and ADRB2 and the high expression of CALCA, GCG, GNGT1, and NPSR1 were correlated with poor OS and poor PFS. The significant differences in the relationship of the expression of 6 hub genes and clinical features were observed. In conclusion, 6 hub genes will not only contribute to elucidating the pathogenesis of LUAD, and may be potential therapeutic targets for LUAD.

Background Concurrent chemoradiotherapy (CCRT) has become the cornerstone of treatment for patients with locally advanced non-small cell lung cancer (LA-NSCLC). The aim of this study was to compare the efficacies and toxicities of different CCRT regimens in the treatment of LA-NSCLC by adopting a network meta-analysis (NMA). Methods An exhaustive search of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted to identify relevant studies from inception to October 1, 2020. Direct and indirect evidence was combined to calculate the odds radios (ORs) and 95% confidence intervals (CIs), as well as to plot the surface under the cumulative ranking (SUCRA) curves. Cluster analyses were adopted to compare the efficacies and toxicities of different CCRT regimens according to the similarity of 2 variables. Publication bias was detected by comparison-adjusted funnel plots. Results Twenty-two studies were enrolled in this NMA, including 18 regimens: CCRT (cisplatin + etoposide), CCRT (carboplatin + paclitaxel), CCRT (pemetrexed + carboplatin), CCRT (pemetrexed + cisplatin), CCRT (docetaxel + cisplatin), CCRT (S-1 + cisplatin), CCRT (mitomycin + vindesine + cisplatin), CCRT (cisplatin + vinorelbine), CCRT (cisplatin), CCRT (etoposide + cisplatin + amifostine), RT, CCRT (5-FU), CCRT (paclitaxel + cisplatin), CCRT (irinotecan + carboplatin), CCRT (nedaplatin), CCRT (carboplatin + etoposide), CCRT (paclitaxel), and CCRT (carboplatin). The results indicated that the regimens with CCRT (cisplatin + etoposide), CCRT (carboplatin + paclitaxel), CCRT (pemetrexed + cisplatin), CCRT (S-1 + cisplatin), and CCRT (cisplatin + vinorelbine) had relatively better efficacies compared with other regimens. As for toxicities of different CCRT regimens, the CCRT (carboplatin + paclitaxel), CCRT (pemetrexed + cisplatin), and CCRT (docetaxel + cisplatin) were relatively lower. Conclusions Our study demonstrated that CCRT (pemetrexed + cisplatin) and CCRT (carboplatin + paclitaxel) might be the best options for the treatment of LA-NSCLC, and CCRT (pemetrexed + cisplatin) had the highest 3-year overall survival (OS) rate.

Background: There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung cancer (NSCLC). Thus, we conducted this meta-analysis to evaluate the clinicopathological features and prognostic significance of NM23 for NSCLC patients.Methods: Pubmed, Embase, and Web of Science were exhaustively searched to identify relevant studies published prior to March, 2020. Odds radios (ORs) and hazard radios with 95% confidence intervals (CIs) were calculated to summarize the statistics of clinicopathological and prognostic assessments. Q-test and I 2 -statistic were utilized to assess heterogeneity across the included studies. We also performed subgroup analyses and meta-regression analyses to identify the source of heterogeneity. Publication bias was detected by Begg and Egger tests. Sensitivity analysis was used to value the stability of our results. All the data were analyzed using statistical packages implemented in R version 4.0.5.Results: Data from a total of 3170 patients from 36 studies were extracted. The meta-analysis revealed that low expression of NM23 was correlated with higher risk of NSCLC (OR = 4.35; 95% CI: 2.76-6.85; P < .01), poorer tumor node metastasis (TNM) staging (OR = 1.39; 95% CI: 1.01-1.90; P = .04), poorer differentiation degree (OR = 1.37; 95% CI: 1.01-1.86; P = .04), positive lymph node metastasis (OR = 1.83; 95% CI: 1.22-2.74; P < .01), lung adenocarcinoma (OR = 1.45; 95% CI: 1.20-1.75; P < .01), and poorer 5-year overall survival (OS) rate (hazard radio = 2.33; 95%CI: 1.32-4.11; P < .01). The subgroup analyses and metaregression analyses suggested that the "Publication year", "Country", "Sample size", and "Cutoff value" might be the source of heterogeneity in TNM staging, differentiation degree, and lymph node metastasis. Both Begg test and Egger test verified that there were publication bias in 5-year OS rate. Sensitivity analysis supported the credibility of the results. Conclusion:The reduced NM23 expression is strongly associated with higher risk of NSCLC, higher TNM staging, poorer differentiation degree, positive lymph node metastasis, lung adenocarcinoma, and poorer 5-year OS rate in NSCLC patients, which indicated that NM23 could serve as a biomarker predicating the clinicopathological and prognostic significance of NSCLC. Abbreviations: CI = confidence interval, EMT = epithelial-mesenchymal transition, HR = hazard radio, IHC = immunohistochemistry, LOH = loss of heterozygosity, LUAD = lung adenocarcinoma, NDPK = nucleoside diphosphate kinase, NM23 = non-metastasis 23, NSCLC = non-small cell lung cancer, OR = odds radio, OS = overall survival, PEDro = Physiotherapy Evidence Database, RCT = randomized controlled trial, RoB = risk of bias.

Keratins (KRTs), a family of genes that encode a series of intermediate flament proteins, which expressed in epithelial cells of various tissues and had been identified as being involved in various tumors. Previous evidences indicated that KRTs were implicated in tumorigenesis and development of lung cancer. However, a comprehensive analysis of KRTs in lung squamous cell carcinoma (LUSC) and their roles in the tumorigenesis and progression of this disease is lacking. Therefore, we investigated the transcriptional level, proteomic level, and prognosis of KRTs in patients with LUSC from TCGA, Gene Expression Profifiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA), Kaplan-Meier Plotter, and cBioPortal databases. We confirmed that the expression levels of KRT5, KRT6A, KRT6B, KRT6C, KRT13, KRT14, KRT15, KRT16, KRT17, KRT19, and KRT23 were higher in LUSC tissues than in adjacent normal lung tissues. Survival analyses using Kaplan-Meier Plotter database and TCGA database revealed that the high expression levels of KRT5, KRT6A, KRT6B, KRT6C, KRT13, KRT14, KRT15, KRT16, KRT17, KRT19, and KRT23 were associated with poor prognosis in patients with LUSC. ROC curves indicated that KRTs had poor roles in predicting the overall survival (OS) of LUSC patients. KRTs and their 50 most frequently altered neighbor genes were mainly enriched in epidermis development, keratinization, keratinocyte differentiation, Rap1 signaling pathway, and transcriptional misregulation in cancer. The results of clinical data analyses indicated that the expression levels of KRT13, KRT16, KRT17, and KRT19 were positively correlated with nodal metastasis, the expression level of KRT15 and KRT17 were positively correlated with primary tumor, and the high expression level of KRT15 was positively correlated with TNM stage. Our study may provide new theoretical basis and research direction for the discovery of potential therapeutic targets and new prognostic biomarkers in patients with LUSC.

Background: Concurrent chemoradiotherapy (CCRT) is the cornerstone treatment for patients with locally advanced non-small cell lung cancer (LA-NSCLC). The aim of this study was to compare the efficacy and toxicity of different CCRT regimens in the treatment of LA-NSCLC by adopting a network meta-analysis.Methods: PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) were exhaustively searched to identify relevant studies from inception up to October 1, 2020. Direct and indirect evidence were combined to calculate the odds radio (OR) and its 95% confidence interval (CI), as well as to draw the surface under the cumulative ranking (SUCRA) curves. Cluster analyses were adopted to compare efficacy and toxicity of different CCRT regimens according to the similarity of 2 variables. Publication bias was detected by comparison-adjusted funnel plot.Results: Twenty-two studies were enrolled in this network meta-analysis, including 18 CCRT regimens: CCRT (cisplatin+etoposide), CCRT (carboplatin+paclitaxel), CCRT (pemetrexed+carboplatin), CCRT (pemetrexed+cisplatin), CCRT (docetaxel+cisplatin), CCRT (S-1+cisplatin), CCRT (mitomycin+vindesine+cisplatin), CCRT (cisplatin+vinorelbine), CCRT (cisplatin), CCRT (etoposide+cisplatin+amifostine), RT, CCRT (5-FU), CCRT (paclitaxel+cisplatin), CCRT (irinotecan+carboplatin), CCRT (nedaplatin), CCRT (carboplatin+etoposide), CCRT (paclitaxel), and CCRT (carboplatin). The results indicated that the regimens with CCRT (cisplatin+etoposide), CCRT (carboplatin+paclitaxel), CCRT (pemetrexed+cisplatin), CCRT (S-1+cisplatin), and CCRT (cisplatin+vinorelbine) had relatively better efficacy compared with other regimens. As for toxicity of different CCRT regimens, the CCRT (carboplatin+paclitaxel), CCRT (pemetrexed+cisplatin), and CCRT (docetaxel+cisplatin) were relatively lower.Conclusions: Our study demonstrated that CCRT (pemetrexed+cisplatin) and CCRT (carboplatin+paclitaxel) might be the best choice of CCRT regimens in the treatment of LA-NSCLC, and the 3-year overall survival (OS) rate of CCRT (pemetrexed+cisplatin) was the highest among these regimens.