Identification of a Novel Oxidative Stress- and Anoikis-Related Prognostic Signature and Its Immune Landscape Analysis in Non-Small Cell Lung Cancer.

The objective of this study was to identify a kind of prognostic signature based on oxidative stress- and anoikis-related genes (OARGs) for predicting the prognosis and immune landscape of NSCLC. Initially, We identified 47 differentially expressed OARGs that primarily regulate oxidative stress and epithelial cell infiltration through the PI3K-Akt pathway. Subsequently, 10 OARGs related to prognosis determined two potential clusters. A cluster was associated with a shorter survival level, lower immune infiltration, higher stemness index and tumor mutation burden. Next, The best risk score model constructed by prognostic OARGs was the Random Survival Forest model, and it included SLC2A1, LDHA and PLAU. The high-risk group was associated with cluster A and poor prognosis, with a higher tumor mutation burden, stemness index and proportion of M0-type macrophages, and a lower immune checkpoint expression level, immune function score and IPS score. The calibration curve and decision-making curve showed that the risk score combined with clinical pathological characteristics could be used to construct a nomogram for guiding the clinical treatment strategies. Finally, We found that all three hub genes were highly expressed in tumor tissues, and LDHA expression was mainly regulated by has-miR-338-3p, has-miR-330-5p and has-miR-34c-5p. Altogether, We constructed an OARG-related prognostic signature to reveal potential relationships between the signature and clinical characteristics, TME, stemness, tumor mutational burden, drug sensitivity and immune landscape in NSCLC patients.

In 18F-positron emission tomography/computed tomography-guided precision radiotherapy for centrally located non-small cell lung cancer, tumor related atelectasis is a prognostic factor of survival.

Purpose: Tumor related atelectasis(TRA) is an essential factor affecting survival that can cause chest pain, cough, hemoptysis, chest tightness, dyspnea, and even death. In the current study, we explored the possible impact of TRA on survival in cancer patients and the guiding significance of 18F-positron emission tomography/computed(PET/CT) in radiotherapy for patients with atelectasis tumors. Methods: In this retrospective study, we analyzed the treatment model and survival of patients with centrally located non-small cell lung cancer(NSCLC) treated with radiotherapy at two medical centers between May 2005 and August 2019. We identified 152 eligible patients and used propensity score matching (1:1) to process the data to reduce confounding factors, data bias, and mal-distribution. Results: We used propensity scores created well-matched groups of 57 patients overall with or without TRA. The one-year survival rate of all patients was 71.9%, and the two-year survival rate was 33.3%. Compared to the atelectasis group, the overall survival (OS) of patients in the non-atelectasis group was significantly prolonged (25 months vs. 17 months, p = 0.004), as well as in the atelectasis recovery group (28 months vs. 14 months, p = 0.008). In multivariate analysis, non-atelectasis was closely correlated with favorable OS (HR, 1.804 (-2.840); 95% CI, 1.145-2.840; p = 0.011). Conclusion: PET/CT can accurately stage NSCLC and better guide the treatment of NSCLC complicated with atelectasis. Tumor-associated atelectasis in patients with centrally located NSCLC can lead to is a poor prognostic marker.

Coexisting EGFR and TP53 Mutations in Lung Adenocarcinoma Patients Are Associated With COMP and ITGB8 Upregulation and Poor Prognosis.

The heterogeneity of lung adenocarcinoma is driven by key mutations in oncogenes. To determine the gene expression, single nucleotide polymorphisms, and co-mutations participating in the initiation and progression of lung adenocarcinoma, we comprehensively analyzed the data of 491 patients from The Cancer Genome Atlas. Using log-rank and Kruskal-Wallis analysis, Oncoprint, Kaplan-Meier survival plots, and a nomogram, we found that EGFRL858R with co-mutation TP53 was significant prognostic determinant versus that with co-wild TP53 (hazard ratio, 2.77, P = 0.012). Further gene co-expression network and functional enrichment analysis indicated that co-mutation of EGFRL858R/TP53 increases the expression of COMP and ITGB8, which are involved in extracellular matrix organization and cell surface receptor signaling pathways, thus contributing to poor prognosis in lung adenocarcinoma. Validation was performed using three GEO profiles along with colony formation and CCK-8 assays for proliferation, transwell and wound-healing for migration in transfected H1299 and A549 cell lines. To the best of our knowledge, these results are the first to indicate that patients harboring the co-mutation of EGFRL858R/TP53 show increased expression of COMP and ITGB8, which participate in extracellular matrix dysfunction and can be used as prognostic biomarkers in patients with lung adenocarcinoma.

Treatment patterns and survival after 18F-fluorodeoxyglucose positron emission tomography/computed tomography-guided local consolidation therapy for oligometastatic non-small cell lung cancer: a two-center propensity score-matched analysis.

PURPOSE: In this retrospective study, we evaluated the treatment patterns and survival after positron emission tomography-computed tomography (PET/CT)-guided local consolidation therapy (LCT) for oligometastatic non-small cell lung cancer (NSCLC). METHODS: We reviewed the medical records of Chinese patients with oligometastatic stage IV non-small cell lung cancer (≤ 5 metastases) who had undergone PET/CT and were eligible for systemic therapy at two centers between May 2005 and August 2019. Propensity score matching (1:1) was used to reduce selection bias and imbalanced distribution of confounding factors. RESULTS: We identified 84 eligible patients and used propensity scores to create well-matched groups of 35 patients who did or did not undergo LCT. Among all patients, the 1-year overall survival (OS) rate was 47.6% and the 2-year OS rate was 22.6%. Relative to the group that did not receive LCT, the LCT group had a significantly higher OS rate (13 months vs. 7 months, p = 0.002). The two groups had similar incidences and classifications of LCT-related side effects. In multivariable analysis, LCT was found to be strongly associated with a favorable OS (hazard ratio: 0.508, 95% confidence interval: 0.311-0.828, p = 0.001). CONCLUSION: We concluded that LCT was significantly associated with improved clinical outcomes among the Chinese patients with oligometastatic NSCLC who were eligible for systemic treatment and could undergo PET/CT evaluation.

p53/miR-30a-5p/ SOX4 feedback loop mediates cellular proliferation, apoptosis, and migration of non-small-cell lung cancer.

Many microRNAs (miRNAs) play vital roles in the tumorigenesis and development of cancers. In this study, we aimed to identify the differentially expressed miRNAs and their specific mechanisms in non-small-cell lung cancer (NSCLC). Based on data from the GSE56036 database, miR-30a-5p expression was identified to be downregulated in NSCLC. Further investigations showed that overexpression of miR-30a-5p inhibited cell proliferation, migration, and promoted apoptosis in NSCLC. Increase of miR-30a-5p level could induce the increase of Bax protein level and decrease of Bcl-2 protein level. In addition, chromatin immunoprecipitation assays showed that miR-30a-5p expression was induced by binding of p53 to the promoter of MIR30A. Bioinformatics prediction indicated that miR-30a-5p targets SOX4, and western blot analysis indicated that overexpression of the miRNA decreases the SOX4 protein expression level, which in turn regulated the level of p53. Thus, this study provides evidence for the existence of a p53/miR-30a-5p/SOX4 feedback loop, which likely plays a key role in the regulation of proliferation, apoptosis, and migration in NSCLC, highlighting a new therapeutic target.

Long Noncoding RNA RAET1K Enhances CCNE1 Expression and Cell Cycle Arrest of Lung Adenocarcinoma Cell by Sponging miRNA-135a-5p.

Molecular dysregulation is believed to participate in the onset and progression of lung adenocarcinoma (LUAD). This study aimed to identify and evaluate the potential key long noncoding RNAs (lncRNAs) involved in the significant dysfunctional process of LUAD. We found that lncRNA retinoic acid early transcript 1K (RAET1K) was upregulated in tumor tissues and were correlated with a poor prognosis of patients with LUAD; further, for the first time, we detected the biological roles of RAET1K. Weighted gene correlation network and gene set enrichment analysis revealed that high RAET1K expression is related to cell cycle dysfunction through upregulated cyclin E1 (CCNE1) by targeting miR-135. The dual-luciferase reporter gene assay was performed to clarify the binding relationship between RAET1K and miR-135a-5p in transgenic A549 and H1299 cells. Real-time PCR and Western blot analyses showed that RAET1K overexpression and miR-135a-5p inhibition exerted a strong synergistic effect on CCNE1 expression, and cell cycle flow cytometry analysis was used to confirm the arrest of A549 and H1299 cells at the G1/S phase. The lncRNA RAET1K/miR-135a-5p axis might participate in the regulation of LUAD progression by influencing CCNE1 expression and the accumulation of cells arrested at the G1/S phase boundary.

CHL1 gene polymorphisms increase lung cancer susceptibility.

Lung cancer represents a complex and malignant cancer. Close Homologue of L1 (CHL1) gene plays a crucial role in the progress of cancer. The aim of this study is to explore the association between CHL1 rs425366 polymorphism and lung cancer susceptibility in northeast of China. A hospital-based case-control study was carried out to collect relative characteristics. Logistic regression analysis was conducted to analyze the relationship between single nucleotide polymorphisms and lung cancer susceptibility. The results suggested that there was statistically significant difference between GT genotype and TT genotype of rs425366 and lung cancer susceptibility. In stratified analysis, TT genotype of rs425366 may increase the risk of lung adenocarcinoma. We also found that non-smoking individuals carrying T allele were more likely to develop lung cancer. Overall, our study may indicate that CHL1 gene may increase lung cancer susceptibility in northeast of China.

Dual-specificity phosphatase 6 genetic variants associated with risk of lung squamous cell carcinoma in Han Chinese.

BACKGROUND: Nonsmall cell lung cancer (NSCLC) mainly contains adenocarcinoma (AC) and squamous cell carcinoma (SqCC). This study investigated single nucleotide polymorphism (SNP) of topoisomerase II alpha (TOP2A) and dual-specificity phosphatase 6 (DUSP6) in a hospital-based case and control cohort of individuals for association with risk of different histological subtypes of NSCLC. MATERIALS AND METHODS: A total of 454 (237 SqCC and 217 AC) NSCLC patients, and 454 healthy controls were recruited for analysis of TOP2A rs471692 and DUSP6 rs2279574 genotypes using the TaqMan polymerase chain reaction technique. RESULTS: TOP2A rs471692 and DUSP6 rs2279574 SNPs were in complete linkage disequilibrium; however, frequency of DUSP6 rs2279574 genotype was significantly different between the case and control, that is, DUSP6 rs2279574a/A and A/C genotypes might contribute to an increased risk of lung squamous carcinoma compared with the C/C genotype. Moreover, DUSP6 rs2279574 AA genotype was also significantly associated with advanced stages of lung cancer. In contrast, frequency of the TOP2A rs471692 genotype had no association between cases and controls (P = 0.906). Genotype frequency of DUSP6 rs2279574 was 11.9% for C/C, 43.6% for C/A, and 44.5% for A/A in the case versus 16.7% C/C, 43.4% C/A, and 39.9% A/A in the control population (χ2 = 3.136, P= 0.077 by Hardy-Weinberg equilibrium test [HWE]). The genotype frequency of TOP2A rs471692 was 50.0% for C/C, 41.6% for C/T, and 8.4% for T/T in the case versus 50.2% C/C, 43.0% C/T, and 6.8% T/T in the control populations (χ2 = 0.023, P= 0.879 by HWE test). CONCLUSION: Individuals are carrying DUSP6 rs2279574 AA and AC genotypes associated with an increased risk in developing lung squamous carcinoma in Han Chinese and with advanced NSCLC stages.

Associations of miR-605 rs2043556 polymorphism with the susceptibility and overall survival of lung cancer in Chinese non-smoking females.

The effects of miR-605 rs2043556 single nucleotide polymorphism (SNP) on the risk and prognosis of lung cancer are unclear. This study investigated the relationships between miR-605 rs2043556 and the susceptibility and overall survival (OS) of lung cancer in Chinese non-smoking females. This hospital-based case-control study included 450 cases and 450 controls. Also, a prospective cohort study was carried out, and the patients were followed up until February 29th, 2016. There were 334 patients with prognostic information. Odds ratio and hazard ratio (HR) and their 95% confidence intervals (CIs) were calculated, respectively. In squamous cell carcinomas (SqCC) patients, homozygous GG genotype carriers had a 2.157-fold elevated risk of lung cancer compared with homozygous AA genotype carriers after adjusting age (95% CI = 1.029-4.524, P = 0.042). After adjusting age, pathological type, clinical stage, chemotherapy and surgery, only a marginal significance was observed among the patients with GG genotype, who had a longer OS than those with AA genotype (HR = 0.632, 95% CI = 0.398-1.003, P = 0.051). For patients younger than 60 years, those containing GG genotype was independently associated with OS (HR = 0.511, 95% CI = 0.268-0.977, P = 0.042). Patients with adenocarcinomas containing GG genotype was independently associated with OS (HR = 0.530, 95% CI = 0.312-0.898, P = 0.018). MiR-605 rs2043556 polymorphism could be associated with the susceptibility of SqCC in northeast Chinese non-smoking females. Age and pathological type might have the potential to modify the association between miR-605 rs2043556 and the OS of non-smoking female lung cancer patients.

Polymorphisms of rs1347093 and rs1397529 are associated with lung cancer risk in northeast Chinese population.

Lung cancer is one of the malignant tumors with the highest morbidity and mortality all over the world. Here we researched the association between two SNPs (rs1347093 in MIR217HG and rs1397529 in Gab1) and the risk of lung cancer in northeast Chinese population, including 825 cases and 766 controls. We carried out χ2 test, unconditional logistic regression analysis and crossover analysis to estimate the relationship between SNPs and lung cancer risk and the interaction between SNPs and smoking on susceptibility to lung cancer. The results indicated that rs1347093, rs1397529 polymorphisms were associated with lung cancer risk, especially with adenocarcinoma risk. Dominant genetic model of the rs1347093 was associated with reduced risk of lung cancer compared to CC genotype (AC+AA vs. CC: adjusted OR = 0.599, 95%CI = 0.418-0.858, P=0.005). For rs1347093, the similar result was found. Dominant genetic model of the rs1397529 was associated with reduced risk of lung cancer compared to AA genotype (AC+CC vs. AA: adjusted OR = 0.664, 95%CI = 0.491-0.897, P=0.008). There is no significant interaction between rs1347093, rs1397529 polymorphism and smoking on susceptibility to lung cancer. Our study might demonstrate that rs1347093 in MIR217HG and rs1397529 in Gab1 could be meaningful as the novel biomarker for lung cancer risk.

Association of PPP1R13L and CD3EAP polymorphisms with risk and survival of non-small cell lung cancer in Chinese non-smoking females.

PPP1R13L and CD3EAP were confirmed to play important roles in transcription and apoptosis. SNPs in PPP1R13L and CD3EAP may be associated with lung cancer risk and survival. This study investigated the association of PPP1R13L rs1005165 and CD3EAP rs967591 with non-small cell lung cancer (NSCLC) risk and survival in Chinese non-smoking females. 442 NSCLC cases and 480 cancer-free controls were conducted in the case-control study, and 283 cases were in cohort study. Genotype was determined by Taqman real-time PCR. The statistical analyses were performed by SPSS 22.0 software. We found that rs1005165 and rs967591 were significantly associated with NSCLC risk in Chinese non-smoking females. For rs1005165, compared with homozygous wild CC genotype, carriers of CT or TT genotype had lower risk of NSCLC (adjusted ORs were 0.675 and 0.713, 95% CI were 0.461-0.988 and 0.525-0.968, respectively), adjusted OR for dominant model was 0.702, 95% CI was 0.526-0.937. For rs967591, AA genotype (adjusted OR = 0.721, 95% CI = 0.532-0.978) and at least one A allele (GA+AA) (adjusted OR = 0.716, 95% CI = 0.536-0.956) were significantly correlated with lower risk of NSCLC, compared with GG genotype. But we didn't find correlation between the two SNPs and survival time in Chinese non-smoking NSCLC females. In general, we found PPP1R13L rs1005165 and CD3EAP rs967591 might be associated with lower NSCLC risk in Chinese non-smoking females, but no significant relationship was found with NSCLC survival.

Genetic polymorphisms in pre-miRNAs predict the survival of non-small-cell lung cancer in Chinese population: a cohort study and a meta-analysis.

BACKGROUND: To explore the association of genetic polymorphisms in pre-miRNA 30c-1 rs928508 and pre-miRNA 27a rs895819 with non-small-cell lung cancer prognosis. MATERIALS AND METHODS: 480 patients from five hospitals were enrolled in this prospective cohort study. They were followed up for five years. The association between genotypes and overall survival was assessed by Cox proportional hazards regression models. A meta-analysis was conducted to provide evidence for the effect of microRNA 27a rs895819 on cancer survival. RESULTS: G-allele containing genotypes of microRNA 30c-1 polymorphisms and C-allele containing genotypes of microRNA 27a were significantly associated with poorer overall survival. Multivariate Cox regression models indicated that these genetic polymorhpisms were independently predictive factors of poorer overall survival. In stratified analysis, the effect was observed in many strata. The significant joint effect was also observed in our study. Patients with G allele of microRNA 30c-1 rs928508 and C allele of microRNA 27a rs895819 had the poorer overall survival than patients with C allele of rs928508 and T allele of rs895819. The effect of the microRNA 27a rs895819 on non-small cell lung cancer overall survival was supported by the meta-analysis results. CONCLUSIONS: The two single nucleotide polymorphisms in microRNA 30c-1 and microRNA 27a can predict the outcome of non-small cell lung cancer patients and they may decrease the sensitivity to anti-cancer drugs.

MiR-196a2 and lung cancer in Chinese non-smoking females: a genetic association study and expression analysis.

BACKGROUND: The common polymorphism rs11614913 in miR-196a2 might be associated with lung cancer risk for non-smoking females in northeast China. METHODS: The genotypes of rs11614913 in miR-196a2 were determined by a case-control study including 1003 patients with lung cancer and 1003 healthy controls. The tissues were detected to assess the miRNA expression. Secondary structures of miR-196a2 were predicted. RESULTS: There was a significant association between miR-196a2 rs11614913 and lung cancer risk in Chinese non-smoking females. Individuals carrying TC or CC genotype had increased risk of lung cancer compared with TT genotype (adjusted risks were 1.63 and 1.67). The C allele was associated with a higher risk of lung cancer with a significant risk of 1.27. The similar significant results were also found in lung adenocarcinoma. There was a significant association between miR-196a2 expression and lung cancer risk (t=2.594, P=0.012). The relative expression of miR-196a2 was significantly higher for CC genotype comparing with the CT or TT genotype in tumor tissues (P values were all 0.003). The optimal free energies were different for T allele and C allele. CONCLUSIONS: The polymorphism rs11614913 in miR-196a2 may be associated with lung cancer risks in Chinese non-smoking females through affecting miR-196a2 expression and secondary structure.

Association of Topoisomerase II (TOP2A) and Dual-Specificity Phosphatase 6 (DUSP6) Single Nucleotide Polymorphisms with Radiation Treatment Response and Prognosis of Lung Cancer in Han Chinese.

BACKGROUND Mutations of DNA topoisomerase II (TOP2A) are associated with chemotherapy resistance, whereas dual-specificity phosphatase 6 (DUSP6) negatively regulates members of the mitogen-activated protein (MAP) kinase superfamily to control cell proliferation. This study assessed TOP2A and DUSP6 single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) patients for association with chemoradiotherapy responses and prognosis. MATERIAL AND METHODS A total of 140 Chinese patients with histologically confirmed NSCLC were enrolled and subjected to genotyping of TOP2A rs471692 and DUSP6 rs2279574 using Taqman PCR. An independent sample t test was used to analyze differences in tumor regression after radiotherapy versus SNP risk factors. Kaplan-Meier curves analyzed overall survival, followed by the log-rank test and Cox proportional hazard models. RESULTS There were no significant associations of TOP2A rs471692 and DUSP6 rs2279574 polymorphisms or clinicopathological variables with response to chemoradiotherapy (p>0.05). Comparing overall survival of 87 patients with stage I-III NSCLC treated with radiotherapy or chemoradiotherapy to clinicopathological variables, the data showed that tumor regression, weight loss, clinical stage, and cigarette smoking were independent prognostic predictors (p=0.009, 0.043, 0.004, and 0.025, respectively). Tumor regression rate >0.34 was associated with patent survival versus tumor regression rate ≤0.34 (p=0.007). CONCLUSIONS TOP2A rs471692 and DUSP6 rs2279574 SNPs were not associated with chemoradiotherapy response, whereas tumor regression, weight loss, clinical stage, and cigarette smoking were independent prognostic predictors for these Chinese patients with NSCLC.

MiR-146a polymorphism correlates with lung cancer risk in Chinese nonsmoking females.

This study provides evidence that the common rs2910164 polymorphism in miR-146a strongly correlates with lung cancer risk in nonsmoking females in northeast China. The genotypes of miR-146a rs2910164 were determined in 1131 patients with lung cancer and 1003 healthy control subjects. Tissue samples were used to evaluate the association between miRNA expression and lung cancer risk as well as the correlation between rs2910164 genotypes and miR-146a expression. The secondary structures of the wild-type and variant miR-146a sequences were predicted, and luciferase-based target assays were used to test whether miR-146a bound to tumor necrosis factor receptor associated factor 6 (TRAF6) mRNA. Individuals carrying heterozygous CG genotype of miR-146a rs2910164 had less risk of lung cancer than those carrying homozygous wild CC genotype (OR = 0.76, 95% CI = 0.60-0.98, P = 0.032). We found no significant association between miR-146a expression and lung cancer risk. MiR-146a expression differed in those carrying the CC genotype as compared with the CG or the GG genotype (P = 0.032 and 0.001), and the secondary structure of the C allele differed slightly from the G allele. Significantly lower levels of luciferase activity were observed when the TRAF6 3'UTR was cotransfected with miR-146a-3p carrying the rs2910164 C allele (P = 0.001). Thus, miR-146a rs2910164 polymorphism may influence susceptibility to lung cancer in Chinese nonsmoking females through targeting TRAF6.

Polymorphisms in miR-135a-2, miR-219-2 and miR-211 as well as their interaction with cooking oil fume exposure on the risk of lung cancer in Chinese nonsmoking females: a case-control study.

BACKGROUND: The associations between microRNAs and lung cancer have received increasing attention. This study assess the association between polymorphisms in miR-135a-2, miR-219-2 and miR-211 genes and the risk of lung cancer, as well as the gene-environment interaction between these polymorphisms and cooking oil fume exposure. METHODS: A case-control study featuring 268 cases and 266 controls was conducted. The associations of miR-135a-2 rs10459194, miR-219-2 rs10988341 and miR-211 rs1514035 polymorphisms with the risk of lung cancer were analyzed. The gene-environment interactions were also reported on both additive and multiplicative scales. RESULTS: There were no statistically significant associations between the single-nucleotide polymorphisms (SNPs) and lung cancer or lung adenocarcinoma. The individuals with both a risk genotype of miRNA SNPs and exposure to a risk factor (cooking oil fumes) were at higher risk of lung cancer than those with only one of these two risk factors (odd ratios of 2.208, 1.285 and 1.813 for miR-135a-2 rs10459194; 2.164, 1.209 and 1.806 for miR-219-2 rs10988341; and 2.122, 1.146 and 1.725 for miR-211 rs1514035, respectively). However, the measures of biological interaction indicate that there was no such interaction between the three SNPs and exposure to cooking oil fumes on an additive scale. Logistic regression models also suggested that the gene-environment interactions were not statistically significant on a multiplicative scale. CONCLUSIONS: There were no significant associations between the polymorphisms in miRNAs (miR-26a-1 rs7372209, miR-605 rs2043556 and miR-16-1 rs1022960) and the risk of lung cancer in the Chinese nonsmoking female population. The interactions between these polymorphisms in miRNAs and cooking oil fume exposure were also not statistically significant.

Association of MicroRNA-149 Polymorphism with Lung Cancer Risk in Chinese Non-Smoking Female: A Case-Control Study.

INTRODUCTION: Rs2292832 is a single nucleotide polymorphism located in the precursor of mir-149 and was reported to be associated with varieties of malignancies. So far, the effect of miR-149 rs2292832 polymorphism on lung cancer risk was unclear. In addition, cooking oil fume exposure was demonstrated to be an important environmental risk factor in Chinese female. The aim of the present study was to evaluate the associations of rs2292832 polymorphism, cooking oil fume exposure and multiplicative interaction of cooking oil fume exposure and rs2292832 polymorphism with lung cancer risk in Chinese non-smoking female population. METHODS: The present study was a hospital-based case-control study conducted in Chinese non-smoking females. 555 lung cancer patients and 395 cancer-free controls were interviewed to collect demographic data and exposure status of environmental risk factors, and then donate 10 ml venous blood which was used to be genotyped by Taqman allelic discrimination method. The statistical analyses were performed on SPSS 13.0 software. RESULTS: The association between miR-149 rs2292832 polymorphism and risk of lung cancer(TC vs. TT: OR = 1.006, 95%CI = 0.767-1.321, P = 0.963; CC vs. TT: OR = 0.41, 95%CI = 0.532-1.329, P = 0.458; Dominant model: OR = 0.965, 95%CI = 0.745-1.251, P = 0.788; Recessive model: OR = 0.816, 95%CI = 0.528-1.259, P = 0.357, adjusted for age), non-small cell lung cancer(TC vs. TT: OR = 1.006, 95%CI = 0.767-1.321, P = 0.963; CC vs. TT: OR = 0.841, 95%CI = 0.532-1.329, P = 0.458, adjusted for age), lung adenocarcinoma(TC vs. TT: OR = 0.944, 95%CI = 0.700-1.273, P = 0.707; CC vs. TT: OR = 0.801, 95%CI = 0.485-1.323, P = 0.386, adjusted for age) and squamous cell carcinoma(TC vs. TT: OR = 1.025, 95%CI = 0.641-1.638, P = 0.919; CC vs. TT: OR = 0.792, 95%CI = 0.346-1.813, P = 0.581, adjusted for age) were all not statistically significant. Result of Logistic regression showed that the multiplicative interaction of cooking oil fume exposure and rs2292832 polymorphism was not statistically significant (P = 0.063 for lung cancer and P = 0.064 for lung adenocarcinoma). CONCLUSION: MicroRNA-149 rs2292832 polymorphism may not be associated with lung cancer risk in Chinese non-smoking female.

Dual Specificity Phosphatase 6 (DUSP6) Polymorphism Predicts Prognosis of Inoperable Non-Small Cell Lung Cancer after Chemoradiotherapy.

BACKGROUND: Dual-specificity phosphatase 6 (DUSP6) inactivates different target kinases to regulate cell proliferation and differentiation. Altered DUSP6 expressions or gene polymorphisms are associated with human cancer development including non-small cell lung cancer (NSCLC). DNA topoisomerase II alpha (TOP2A) regulates chromosome condensation and chromatid separation, and altered TOP2A expressions are associated with drug resistance development. This study assessed DUSP6 and TOP2A single nucleotide polymorphisms (SNPs) associated with NSCLC patient survival. METHODS: This study included 152 surgically resected NSCLC patients and 277 chemoradiotherapy treated inoperable cases. DNA samples from each patient were genotyped for DUSP6 and TOP2A SNPs. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model were used to evaluate the association between these variants and NSCLC overall survival. RESULTS: DUSP6 rs2279574 A/A genotype was associated with significantly poor inoperable NSCLC patient overall survival (A/A vs. C/C, adjusted HR = 1.549, 95% CI = 1.019-2.355). Stratification analysis against clinical stage, histology, weight loss, and ECOG performance status revealed that the DUSP6 rs2279574 A/A variant homozygous genotype is associated with a decrease in survival of stage IV NSCLC patients compared to those with the C/C genotype (log-rank, p = 0.003). No association was found among histology, weight loss, and ECOG performance status. Moreover, there was no association of TOP2A SNPs between clinicopathological and survival data. CONCLUSIONS: Data obtained from the current study demonstrated that functional DUSP6 rs2279574 polymorphism was able to predict inoperable NSCLC patient survival after chemoradiotherapy.

Association between polymorphisms in pre-miRNA genes and risk of lung cancer in a Chinese non-smoking female population.

BACKGROUND: MicroRNAs play important roles in the development of human chronic diseases including lung cancer. This is the first case-control study of lung cancer in a non-smoking female population in northeast China, to evaluate the roles of the polymorphisms in pre-miRNAs on risk of lung cancer. METHODS: The genotypes of six polymorphisms in miRNAs were determined in 575 patients with lung cancer and 608 healthy controls who were frequency matched for age. RESULTS: For miR-146a rs2910164, individuals carrying heterozygous CG or homozygous GG genotype had decreased risks of lung cancer compared with those carrying homozygous wild CC genotype (adjusted odds ratios were 0.76 and 0.64, 95% confidence intervals were 0.59-0.99 and 0.46-0.90, P values were 0.039 and 0.010, respectively). G allele of rs2910164 was associated with a lower risk of lung cancer with a significant odds ratio of 0.80. MiR-423 rs6505162CA or AA genotype was associated with significantly decreased risk for lung cancer compared to CC genotype (adjusted odds ratios were 0.77 and 0.54). The significant result was also found in the allele model with odds ratio of 0.75. However, miR-196a2 rs11614913, miR-30c-1 rs928508, miR-608 rs4919510 and miR-27a rs895819 polymorphisms were not significantly associated with lung cancer risks in any models. The similar results were also found in lung adenocarcinoma patients. CONCLUSIONS: These findings suggest that miR-146a rs2910164C>G and miR-423 rs6505162C>A polymorphisms may contribute to genetic susceptibility to lung cancer and lung adenocarcinoma in Chinese non-smoking females.

Polymorphisms in pre-miRNA genes and cooking oil fume exposure as well as their interaction on the risk of lung cancer in a Chinese nonsmoking female population.

BACKGROUND: MicroRNAs (miRNAs) are suggested to be very important in the development of lung cancer. This study assesses the association between polymorphisms in miRNA-related (miR)-26a-1, miR-605, and miR-16-1 genes and risk of lung cancer, as well as the effect of gene-environment interaction between miRNA polymorphisms and cooking fume exposure on lung cancer. METHODS: A case-control study including 268 diagnosed nonsmoking female lung cancer patients and 266 nonsmoking female controls was carried out. Three miRNA polymorphisms (miR-26a-1 rs7372209, miR-605 rs2043556, and miR-16-1 rs1022960) were analyzed. Both additive and multiplicative interactions were assessed. RESULTS: MiR-16-1 rs1022960 may be associated with the risk of lung cancer. Carriers with TT genotype of miR-16-1 rs1022960 were observed to have a decreased risk of lung cancer compared with CC and CT genotype carriers (odds ratio =0.550, 95% confidence interval =0.308-0.983, P=0.044). MiR-26a-1 rs7372209 and miR-605 rs2043556 showed no statistically significant associations with lung cancer risk. There were no significant associations between the three single nucleotide polymorphisms and lung adenocarcinoma. People with exposure to both risk genotypes of miR-26a-1 rs7372209 and cooking oil fumes were more likely to develop lung cancer than those with only genetic risk factor or cooking oil fumes (odds ratios were 2.136, 1.255, and 1.730, respectively). The measures of biological interaction and logistic models indicate that gene-environment interactions were not statistically significant on additive scale or multiplicative scale. CONCLUSION: MiR-16-1 rs1022960 may be associated with the risk of lung cancer in a Chinese nonsmoking female population. The interactions between miRNA polymorphisms (miR-26a-1 rs7372209, miR-605 rs2043556, and miR-16-1 rs1022960) and cooking oil fumes were not statistically significant.