DataSheet1_Genetic Liability to Insomnia and Lung Cancer Risk: A Mendelian Randomization Analysis.PDF

Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer death worldwide, making its prevention an urgent issue. Meanwhile, the estimated prevalence of insomnia was as high as 30% globally. Research on the causal effect of insomnia on lung cancer incidence is still lacking. In this study, we aimed to assess the causality between the genetic liability to insomnia and lung cancer. We performed a two-sample Mendelian randomization analysis (inverse variance weighted) to determine the causality between the genetic liability to insomnia and lung cancer. Subgroup analysis was conducted, which included lung adenocarcinoma and lung squamous cell carcinoma. In the sensitivity analysis, we conducted heterogeneity test, MR Egger, single SNP analysis, leave-one-out analysis, and MR PRESSO. There were causalities between the genetic susceptibility to insomnia and increased incidence of lung cancer [odds ratio (95% confidence interval), 1.35 (1.14–1.59); P, < 0.001], lung adenocarcinoma [odds ratio (95% confidence interval), 1.35 (1.07–1.70); P, 0.01], and lung squamous cell carcinoma [odds ratio (95% confidence interval), 1.35 (1.06–1.72), P, 0.02]. No violation of Mendelian randomization assumptions was observed in the sensitivity analysis. There was a causal relationship between the genetic susceptibility to insomnia and the lung cancer, which was also observed in lung adenocarcinoma and lung squamous cell carcinoma. The underlying mechanism remains unknown. Effective intervention and management for insomnia were recommended to improve the sleep quality and to prevent lung cancer. Moreover, regular screening for lung cancer may be beneficial for patients with insomnia.</p

MOESM3 of Preferable background filtering for next-generation sequencing analysis in non-small cell lung cancer: pericarcinomatous tissues or peripheral blood lymphocytes?

Additional file 3: Figure S1. The distributions of variant allele fraction and number of variant reads for patients with tumor-derived mutations detected in pericarcinomatous tissues. Box plot elements: center line, median; box limits, upper and lower quartiles; whiskers, 1.5 × interquartile range; points, outliers

MOESM2 of Preferable background filtering for next-generation sequencing analysis in non-small cell lung cancer: pericarcinomatous tissues or peripheral blood lymphocytes?

Additional file 2. Additional Methods

Multi-Targeted Antiangiogenic Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer: Meta-Analyses of 20 Randomized Controlled Trials and Subgroup Analyses

<div><p>Background</p><p>Multi-targeted antiangiogenic tyrosine kinase inhibitors (MATKIs) have been studied in many randomized controlled trials (RCTs) for treatment of advanced non-small cell lung cancer (NSCLC). We seek to summarize the most up-to-date evidences and perform a timely meta-analysis.</p><p>Methods</p><p>Electronic databases were searched for eligible studies. We defined the experimental arm as MATKI-containing group and the control arm as MATKI-free group. The extracted data on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) were pooled. Subgroup and sensitivity analyses were conducted.</p><p>Results</p><p>Twenty phase II/III RCTs that involved a total of 10834 participants were included. Overall, MATKI-containing group was associated with significant superior ORR (OR 1.29, 95% CI 1.08 to 1.55, <i>P</i> = 0.006) and prolonged PFS (HR 0.83, 0.78 to 0.90, <i>P</i> = 0.005) compared to the MATKI-free group. However, no significant improvements in DCR (OR 1.08, 1.00 to 1.17, <i>P</i> = 0.054) or OS (HR 0.97, 0.93 to 1.01, P = 0.106) were observed. Subgroup analyses showed that the benefits were predominantly presented in pooled results of studies enrolling previously-treated patients, studies not limiting to enroll non-squamous NSCLC, and studies using MATKIs in combination with the control regimens as experimental therapies.</p><p>Conclusions</p><p>This up-to-date meta-analysis showed that MATKIs did increase ORR and prolong PFS, with no significant improvement in DCR and OS. The advantages of MATKIs were most prominent in patients who received a MATKI in combination with standard treatments and in patients who had previously experienced chemotherapy. We suggest further discussion as to the inclusion criteria of future studies on MATKIs regarding histology.</p></div

MOESM1 of Preferable background filtering for next-generation sequencing analysis in non-small cell lung cancer: pericarcinomatous tissues or peripheral blood lymphocytes?

Additional file 1: Table S1. List of genes in the pan-cancer 1021-gene panel listed according to their target regions. Table S2. Clinical characteristics of tumor-derived mutation detection in pericarcinomatous tissues from 32 enrolled patients with NSCLC

Flow chart of study selection.

<p>Flow chart of study selection.</p

DataSheet2_Genetic Liability to Insomnia and Lung Cancer Risk: A Mendelian Randomization Analysis.xlsx

Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer death worldwide, making its prevention an urgent issue. Meanwhile, the estimated prevalence of insomnia was as high as 30% globally. Research on the causal effect of insomnia on lung cancer incidence is still lacking. In this study, we aimed to assess the causality between the genetic liability to insomnia and lung cancer. We performed a two-sample Mendelian randomization analysis (inverse variance weighted) to determine the causality between the genetic liability to insomnia and lung cancer. Subgroup analysis was conducted, which included lung adenocarcinoma and lung squamous cell carcinoma. In the sensitivity analysis, we conducted heterogeneity test, MR Egger, single SNP analysis, leave-one-out analysis, and MR PRESSO. There were causalities between the genetic susceptibility to insomnia and increased incidence of lung cancer [odds ratio (95% confidence interval), 1.35 (1.14–1.59); P, < 0.001], lung adenocarcinoma [odds ratio (95% confidence interval), 1.35 (1.07–1.70); P, 0.01], and lung squamous cell carcinoma [odds ratio (95% confidence interval), 1.35 (1.06–1.72), P, 0.02]. No violation of Mendelian randomization assumptions was observed in the sensitivity analysis. There was a causal relationship between the genetic susceptibility to insomnia and the lung cancer, which was also observed in lung adenocarcinoma and lung squamous cell carcinoma. The underlying mechanism remains unknown. Effective intervention and management for insomnia were recommended to improve the sleep quality and to prevent lung cancer. Moreover, regular screening for lung cancer may be beneficial for patients with insomnia.</p

Meta-analyses of MATKIs-containing regimens versus MATKIs-free regimens.

<p>A, ORR; B, DCR; C, PFS; D, OS.</p

Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

<div><p>Backgrounds</p><p>It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered.</p><p>Methods</p><p>Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively.</p><p>Results</p><p>A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation  = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation  = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies.</p><p>Conclusions</p><p>For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs.</p></div

Direct comparison of EGFR exon 19 deletions versus EGFR exon 21 L858R mutations in TKI therapy cohort in terms of HR for PFS. CI = confidence interval; EGFR = epidermal growth factor receptor; HR = Hazard ratio; PFS = progression-free survival; TKI = tyrosine kinase inhibitor.

<p>Direct comparison of EGFR exon 19 deletions versus EGFR exon 21 L858R mutations in TKI therapy cohort in terms of HR for PFS. CI  =  confidence interval; EGFR  =  epidermal growth factor receptor; HR  =  Hazard ratio; PFS  =  progression-free survival; TKI  =  tyrosine kinase inhibitor.</p