Clinicopathological and Demographical Characteristics of Non-Small Cell Lung Cancer Patients with ALK Rearrangements: A Systematic Review and Meta-Analysis

<div><p>Objective</p><p>This meta-analysis aimed to comprehensively examine the relationship between the clinicopathological and demographical characteristics and ALK rearrangements in patients with non-small cell lung cancer (NSCLC).</p><p>Methods and Main Findings</p><p>In total, 62 qualified articles including 1178 ALK rearranged cases from 20541 NSCLC patients were analyzed, and the data were extracted independently by two investigators. NSCLC patients with ALK rearrangements tended to be younger than those without (mean difference: −7.16 years; 95% confidence interval (95% CI): −9.35 to −4.96; P<0.00001), even across subgroups by race. Compared with female NSCLC patients, the odds ratio (OR) of carrying ALK rearrangements was reduced by 28% (95% CI: 0.58–0.90; P = 0.004) in males, and this reduction was potentiated in Asians, yet in opposite direction in Caucasians. Likewise, smokers were less likely to have ALK rearrangements than never-smokers (OR = 0.33; 95% CI: 0.25–0.44; P<0.00001), even in race-stratified subgroups. Moreover, compared with NSCLC patients with tumor stage IV, ALK rearrangements were underrepresented in those with tumor stage I–III (OR = 0.58; 95% CI: 0.44–0.78; P = 0.0002). Patients with lung adenocarcinomas had a significantly higher rate of ALK rearrangements (7.2%) than patients with non-adenocarcinoma (2.0%) (OR = 2.25; 95% CI: 1.54–3.27; P<0.0001).</p><p>Conclusion</p><p>Our findings demonstrate that ALK rearrangements tended to be present in NSCLC patients with no smoking habit, younger age and tumor stage IV. Moreover, race, age, gender, smoking status, tumor stage and histology might be potential sources of heterogeneity.</p></div

Forest plots of gender difference between NSCLC patients with and without ALK rearrangements by race.

<p>Forest plots of gender difference between NSCLC patients with and without ALK rearrangements by race.</p

Clinicopathological and demographical characteristics of NSCLC patients with ALK rearrangements.

<p><i>Abbreviations:</i> NSCLC, non-small-cell lung cancer; Ad, adenocarcinoma; SCC, squamous cell carcinoma; OR, odds ratio; WMD, weighted mean difference; CI, confidence interval.</p

Forest plots of the mean difference of age between NSCLC patients with and without ALK rearrangements by race.

<p>Forest plots of the mean difference of age between NSCLC patients with and without ALK rearrangements by race.</p

Flow diagram of search strategy and study selection.

<p>Flow diagram of search strategy and study selection.</p

Association of Six Well-Characterized Polymorphisms in TNF-α and TNF-β Genes with Sarcoidosis: A Meta-Analysis

<div><p>Backgrounds</p><p>In this study, we aimed to investigate the association of six well-characterized polymorphisms in tumor necrosis factor alpha and beta (TNF-α and TNF-β) genes with the risk for sarcoidosis via a comprehensive meta-analysis.</p> <p>Methods And Findings</p><p>The electronic MEDLINE (Ovid) and PubMed databases covering the period from the earliest possible year to June 2013 were searched. Total 13 qualified articles including 1584 patients with sarcoidosis and 2636 controls were recruited. The data were analyzed by RevMan software, and risk estimates were expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses of the full data set failed to identify any significant association of TNF-α gene -307A (OR=1.25; 95% CI: 0.98-1.59), -1031C (OR=0.88; 95% CI: 0.71-1.1), -863A (OR=0.89; 95% CI: 0.72-1.11), -238A (OR=0.97; 95% CI: 0.71-1.32), and -857T (OR=1.14; 95% CI: 0.74-1.77) alleles, but a significant association for TNF-β 252A allele (OR=1.65; 95%CI = 1.33-2.04; P<0.00001). Under a random-effects allelic model, there was marginally significant increased risk of sarcoidosis for -307A allele among Caucasians (OR=1.25; 95% CI: 0.96-1.62; P=0.09) but not among Asians (OR=2.12; 95% CI: 0.31-14.27; P=0.44). There was a low probability of publication bias as reflected by the fail-safe number.</p> <p>Conclusions</p><p>This meta-analysis extended previous findings on the association between the TNF-α and TNF-β genetic polymorphisms and sarcoidosis, by showing that the TNF-β gene A252G polymorphism might be a potential risk factor for the development of sarcoidosis.</p> </div

Flow diagram of search strategy and study selection.

<p>Flow diagram of search strategy and study selection.</p

Pooled risk estimates of TNF-α gene G-307A, T-1031C, C-863A, G-238A, C-857T polymorphisms, and TNF-β gene A252G polymorphism in association with sarcoidosis under allelic model.

<p>Pooled risk estimates of TNF-α gene G-307A, T-1031C, C-863A, G-238A, C-857T polymorphisms, and TNF-β gene A252G polymorphism in association with sarcoidosis under allelic model.</p

Pooled risk estimates of TNF-α gene G-307A polymorphism in association with sarcoidosis under allelic model by ethnicity.

<p>Pooled risk estimates of TNF-α gene G-307A polymorphism in association with sarcoidosis under allelic model by ethnicity.</p

Data Summary of qLAMP and culture assays.

<p>Note: The Abbreviations are: Ab, <i>A. baumannii</i>; Ec, <i>E. coli</i>; Hi, <i>H. influenzae</i>; Kp, <i>K. pneumoniae</i>; Pa, <i>P. aeruginosa</i>; Sa, <i>S. aureus</i>; Sm, <i>S. maltophilia</i>; and Sp, <i>S. pneumonia</i>.</p>*<p>indicates the number of patients whose positive culture was confirmed by one of the 4 culture-based tests.</p>**<p>indicate confirmation rate of the positive cultures by one of the 4 culture-based tests.</p>***<p>indicate the bacterial mortality due to refrigeration, storage, and transportation.</p