BackgroundLung adenocarcinoma is a heterogernous disease that creates challenges for classification and management. The purpose of this study is to identify specific miRNA markers closely associated with the survival of LUAD patients from a large dataset of significantly altered miRNAs, and to assess the prognostic value of this miRNA expression profile for OS in patients with LUAD.MethodsWe obtained miRNA expression profiles and corresponding clinical information for 372 LUAD patients from The Cancer Genome Atlas (TCGA), and identified the most significantly altered miRNAs between tumor and normal samples. Using survival analysis and supervised principal components method, we identified an eight-miRNA signature for the prediction of overall survival (OS) of LUAD patients. The relationship between OS and the identified miRNA signature was self-validated in the TCGA cohort (randomly classified into two subgroups: n = 186 for the training set and n = 186 for the testing set). Survival receiver operating characteristic (ROC) analysis was used to assess the performance of survival prediction. The biological relevance of putative miRNA targets was also analyzed using bioinformatics.ResultsSixteen of the 111 most significantly altered miRNAs were associated with OS across different clinical subclasses of the TCGA-derived LUAD cohort. A linear prognostic model of eight miRNAs (miR-31, miR-196b, miR-766, miR-519a-1, miR-375, miR-187, miR-331 and miR-101-1) was constructed and weighted by the importance scores from the supervised principal component method to divide patients into high- and low-risk groups. Patients assigned to the high-risk group exhibited poor OS compared with patients in the low-risk group (hazard ratio [HR] = 1.99, P <0.001). The eight-miRNA signature is an independent prognostic marker of OS of LUAD patients and demonstrates good performance for predicting 5-year OS (Area Under the respective ROC Curves [AUC] = 0.626, P = 0.003), especially for non-smokers (AUC = 0.686, P = 0.023).ConclusionsWe identified an eight-miRNA signature that is prognostic of LUAD. The miRNA signature, if validated in other prospective studies, may have important implications in clinical practice, in particular identifying a subgroup of patients with LUAD who are at high risk of mortality.

BackgroundExcision repair cross-complementing group 1 (ERCC1) and group 2 (ERCC2), and X-ray repair cross-complementing group 1 (XRCC1) proteins play important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence treatment effect and survival of cancer patients. This study aimed to investigate the relationship between polymorphisms in ERCC2, ERCC1 and XRCC1 genes and survival of non-smoking female patients with lung adenocarcinoma.MethodsWe used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to evaluate SNPs in ERCC2, ERCC1 and XRCC1 genes among 257 patients.ResultsThe overall median survival time (MST) was 13.07 months. Increasing numbers of either ERCC1 118 or XRCC1 399 variant alleles were associated with shorter survival of non-smoking female lung adenocarcinoma patients (Log-rank P < 0.001). The adjusted hazard ratios (HRs) for individuals with CT or TT genotype at ERCC1 Asn118Asn were 1.48 and 2.67 compared with those with CC genotype. For polymorphism of XRCC1 399, the HRs were 1.28 and 2.68 for GA and AA genotype. When variant alleles across both polymorphisms were combined to analysis, the increasing number of variant alleles was associated with decreasing overall survival. Using the stepwise Cox regression analysis, we found that the polymorphisms in ERCC1 and XRCC1, tumor stage and chemotherapy or radiotherapy status independently predicted overall survival of non-smoking female patients with lung adenocarcinoma.ConclusionsGenetic polymorphisms in ERCC1 and XRCC1 genes might be prognostic factors in non-smoking female patients with lung adenocarcinoma.

These data suggest that Notch3 activation cooperatively takes part in the LiCl-induced cell cycle changes, at least partially, associated with c-MYC, Skp2 and p21.

Short-term exposures to air pollution are associated with acute effects on respiratory health. This study aimed to describe 10-year temporal trends in respiratory mortality in the urban areas of Shenyang, China, according to gender and age and estimate the effects of air pollution on respiratory diseases (ICD-10J00-J99) and lung cancer (ICD-10 C33-C34) using a case-crossover design. During the study period 2013–2015, the exposure-response relationship between ambient air pollutants and mortality data was fitted by a quasi-Poisson model. Age-standardized mortality rates for a combined number of respiratory diseases and for lung cancer declined in Shenyang; however, death counts increased with aging. Deaths from respiratory diseases increased by 4.7% (95% CI, 0.00–9.9), and lung cancer mortality increased by 6.5% (95% CI, 1.2–12.0), both associated with a 10 μg/m3 increase in exposure to particulate matter < 2.5 μg in diameter (PM2.5). Moreover, males in Shenyang’s urban areas were more susceptible to the acute effects of PM2.5 and SO2 exposure; people aged ≥ 65 years had a high susceptibility to ozone, and those aged < 65 years were more susceptible to other air pollutants. These results provided an updated estimate of the short-term effects of air pollution in Shenyang. Since population aging is also associated with increasing mortality from respiratory diseases and lung cancer, reinforcing air quality control measures and health-promoting behaviors is urgent and necessary in Shenyang.Electronic supplementary materialThe online version of this article (10.1007/s11356-018-1270-5) contains supplementary material, which is available to authorized users.

No abstract