Construction of long non-coding RNA- and microRNA-mediated competing endogenous RNA networks in alcohol-related esophageal cancer.

The current study aimed to explore the lncRNA-miRNA-mRNA networks associated with alcohol-related esophageal cancer (EC). RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas and the differentially expressed genes (DEGs), long non-coding RNAs (lncRNAs, DELs), and miRNAs (DEMs) in patients with alcohol-related and non-alcohol-related EC were identified. Prognostic RNAs were identified by performing Kaplan-Meier survival analyses. Weighted gene co-expression network analysis was employed to build the gene modules. The lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks were constructed based on our in silico analyses using data from miRcode, starBase, and miRTarBase databases. Functional enrichment analysis was performed for the genes in the identified ceRNA networks. A total of 906 DEGs, 40 DELs, and 52 DEMs were identified. There were eight lncRNAs and miRNAs each, including ST7-AS2 and miR-1269, which were significantly associated with the survival rate of patients with EC. Of the seven gene modules, the blue and turquoise modules were closely related to disease progression; the genes in this module were selected to construct the ceRNA networks. SNHG12-miR-1-ST6GAL1, SNHG3-miR-1-ST6GAL1, SPAG5-AS1-miR-133a-ST6GAL1, and SNHG12-hsa-miR-33a-ST6GA interactions, associated with the N-glycan biosynthesis pathway, may have key roles in alcohol-related EC. Thus, the identified biomarkers provide a novel insight into the molecular mechanism of alcohol-related EC.

EGFR mutation status in non-small cell lung cancer receiving PD-1/PD-L1 inhibitors and its correlation with PD-L1 expression: a meta-analysis.

Meta-analysis was performed on the Web of Science, PubMed, Embase, and Cochrane databases to evaluate the effect of epidermal growth factor receptor (EGFR) mutation status on programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors, and the association between EGFR mutation status and PD-L1 expression in non-small cell lung cancer (NSCLC) patients. Pooled effect (hazard ratio/odds ratio, HR/OR) with 95% confidence interval (CI) was calculated, and the source of heterogeneity was explored by subgroup analysis and meta-regression using Stata/SE 15.0. Meta-analysis of the association between EGFR mutation status and overall survival (OS) in NSCLC with immunotherapy was calculated from four randomized controlled trials. We found that immune checkpoint inhibitors significantly prolonged OS over docetaxel overall (HR 0.71, 95% CI 0.64-0.79) and in the EGFR wild type (HR = 0.67, 95% CI = 0.60-0.75), but not in the EGFR mutant subgroup (HR = 1.11, 95% CI = 0.80-1.52). Meta-analysis of the association between EGFR mutation status and PD-L1 expression in NSCLC included 32 studies. The pooled OR and 95% CI were 0.60 (0.46-0.80), calculated by random effects model. No source of heterogeneity was found in subgroup analysis. Sensitivity analysis was carried out with a fixed model, and the influence of a single study on the pooled results showed no significant change with robust meta-analysis methods. Harbord's weighted linear regression test (P = 0.956) and Peters regression test (P = 0.489) indicated no significant publication bias. The limited benefit of single-agent PD-1/PD-L1 inhibitors in the second-line or later setting for EGFR-mutated NSCLC may be partly due to the lower expression of PD-L1.

Combined effects of lung disease history, environmental exposures, and family history of lung cancer to susceptibility of lung cancer in Chinese non-smokers.

BACKGROUND: Although cigarette smoking is a major risk factor for lung cancer, the incidence rate of lung cancer among non-smokers is notable. The etiology and potential mechanism of non-smoker lung cancer are worthy of further research. This study was designed to explore the collective effects of environmental factors and the relationship between environmental exposure index (EEI) and lung cancer among non-smokers by evaluating the joint effects among lung disease history, environmental factors, and family history of lung cancer without smoking confounders. METHODS: A total of 767 never-smoked lung cancer cases and 767 sex- and age-matched controls were selected from the department of Thoracic Surgery and Respiratory Medicine of three hospitals in Fujian, China. We used two methods to develop the EEI according to 12 statistically significant environmental risk factors. Restricted cubic spline (RCS) was applied to analyze the non-linear relationship between EEI and lung cancer in non-smokers. Combined effects, additive interaction, and multiplicative interaction were assessed among lung disease history, EEI, and family history of lung cancer to estimate susceptibility to develop lung cancer. RESULTS: Lung disease history, especially asthma, was significantly associated with an increased risk of lung cancer with an odds ratio (OR) for asthma history of 14.720 (95% CI: 1.877-115.449). Family history of lung cancer was related to susceptibility of lung cancer (OR = 3.347, 95% CI: 1.930-5.806). According to type of relatives and cancer, a parental or children's history and a sibling's history of lung cancer were significantly associated with an increased risk of lung cancer. The positive association between EEI and lung cancer was apparently stronger in those with lung disease history or family lung cancer history. Furthermore, there was a addictive interaction between EEI and lung disease history, and a possibly addictive interaction between EEI and family lung cancer history on development of lung cancer. CONCLUSIONS: There were combined effects among lung disease history, environmental exposures, and family history of lung cancer toward susceptibility to lung cancer in Chinese non-smokers. Non-smokers who had a family history of lung cancer were at higher risk of lung cancer than non-smokers who had lung disease history. Non-smokers with family cancer history may obtain benefits from removal of environmental exposures and active treatment of lung disease.

POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1.

BACKGROUND: To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. METHODS: Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. RESULTS: We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients' prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. CONCLUSION: We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

Microarray profiling of differentially expressed lncRNAs and mRNAs in lung adenocarcinomas and bioinformatics analysis.

Long noncoding RNAs (lncRNAs) dysregulation leads to malignant progression of lung cancer. Our study profiled differentially expressed lncRNA and mRNA in tumor and normal tissues of lung adenocarcinoma (LUAD). Further, analysis of the gene expression profiles of LUAD tissues (n = 533) and normal tissues (n = 59) from The Cancer Genome Atlas (TCGA). A total of 138 lncRNAs were differentially expressed between LUAD tissues and normal tissues (false discovery rate [FDR] q < 0.05, fold change (FC) ≥ 2), a number of which are key regulators of multiple cancer and biological processes in humans. For example, lncRNA A2M-AS1 displayed the highest correlation with the co-expressed mRNAs, indicating that it might play a key role in regulating differential gene expression in LUAD. The data from the current study of the comprehensive lncRNA expression profile in LUAD tissues provided useful information to guide the identification of potential LUAD biomarkers.

Human papillomavirus infection maybe not associated with primary lung cancer in the Fujian population of China.

BACKGROUND: To investigate whether human papillomavirus (HPV) infection is associated with primary lung cancer among the Fujian population. METHODS: HPV infection was detected in 140 pairs of lung cancer tissues and matched paracancerous tissues by examining the 21 clinically relevant HPV types using a combination of viral highly conserved L1 region PCR amplification and specific probe reverse hybridization. Paired χ2 test was used to analyze differences in detection rates of HPV between lung cancer and paracancerous tissues. Differences in detection rates of HPV in lung cancer tissues were analyzed using χ2 test or the exact probability method. The rank sum test was used to analyze differences in the distributions of routine indices of blood and pulmonary function in lung cancer tissues between the HPV negative and positive groups. RESULTS: HPV infection was detected in 13 of the 140 tumor specimens and in 16 of the paired normal lung tissues. There was no significant correlation between HPV infection and lung cancer (P > 0.05). The diagnosed HPV infection rates did not differ significantly among lung cancer tissues with different stratification (P > 0.05). However, the platelet count, platelet pressure, residual gas volume, functional residual volume, and residual gas volume/lung total distribution may differ between HPV-negative and HPV-positive lung cancer tissues (0.000625 < P < 0.05). CONCLUSIONS: We concluded that HPV infection may not be associated with the risk of primary lung cancer in the Fujian population. However, HPV infection may affect platelet and residual lung function in primary lung cancer patients.

Genome-wide DNA methylation and RNA expression profiles identified RIPK3 as a differentially methylated gene in Chlamydia pneumoniae infection lung carcinoma patients in China.

Aim: To explore the relationship between Chlamydia pneumonia (Cpn) infection and lung cancer using integrative methylome and transcriptome analyses. Methods: Twelve primary lung cancer patients who were positive for Cpn and twelve patients who were negative were selected for demographic, clinicopathological, and lifestyle matching. Genomic DNA and RNA were extracted and DNA methylation and mRNA levels were detected using the Infinium Human Methylation 450 Beadchip array and mRNA + lncRNA Human Gene Expression Microarray. We identified differentially expressed methylation and genes profiles. Results: Integrative analysis revealed an inverse correlation between differentially expressed genes and DNA methylation. Cpn-related lung cancer methylated genes (target genes) were introduced into the gene ontology and KEGG, PID, BioCarta, Reactome, BioCyc and PANTHER enrichment analyses using a q-value cutoff of 0.05 to identify potentially functional methylation of abnormal genes associated with Cpn infection. Gene sets enrichment analysis was evaluated according to MsigDB. Levels of differentially expressed methylated sites were quantitatively verified. The promoter methylation sites of 62 genes were inversely related to expression levels. According to the quantitative analysis of DNA methylation, the methylation level of the RIPK3 promoter region was significantly different between Cpn-positive cancerous and adjacent tissues, but not between Cpn-negative cancerous and adjacent tissues. Conclusion:  Hypomethylation of the RIPK3 promoter region increases RIPK3 expression, leading to regulated programmed necrosis and activation of NF-κB transcription factors, which may contribute to the development and progression of Cpn-related lung cancer.

Association between single nucleotide polymorphisms of NOTCH signaling pathway-related genes and the prognosis of NSCLC.

OBJECTIVE: In this study, we analyzed the association between genetic variants of genes in the NOTCH signaling pathway and the prognosis of non-small-cell lung cancer (NSCLC) in the Chinese population. We also explored the interaction between genetic and epidemiological factors for the test group. METHODS: We performed genotyping of 987 NSCLC patients. Then, we used Cox proportional hazard models to analyze the associations between single-nucleotide polymorphisms (SNPs) and the prognosis of NSCLC. We employed Stata software to test the heterogeneity of associations between subgroups, and we analyzed the additive and multiplicative interactions between SNPs and epidemiologic factors. RESULTS: This work revealed the important prognostic and predictive value of rs915894 in the NOTCH4 gene, which may be regarded as a promising prognosis biomarker of NSCLC. Cox regression analysis indicated that the C allele of rs915894 is associated with longer survival and decreased risk of death in NSCLC (codominant model: adjusted HR =0.83, 95% CI =0.70-0.99; dominant model: adjusted HR =0.83, 95% CI =0.71-0.98). Additional stepwise regression analysis suggested that this SNP is an independently favorable factor for the prognosis of NSCLC (dominant model: adjusted HR =0.85, 95% CI =0.72-0.99). This protective effect is more pronounced for patients who are not smokers, have a history of other lung diseases, or have a family history of cancer. We also detected statistically significant additive and multiplicative interactions between rs915894 and smoking, rs915894 and history of lung diseases, and rs915894 and family history of cancer, which all affect NSCLC survival. CONCLUSION: This study demonstrated that rs915894 in NOTCH 4 may be a genetic marker for NSCLC prognosis in the Chinese population and that rs915894 may have an interactive relationship with epidemiologic factors.

Dietary patterns, BCMO1 polymorphisms, and primary lung cancer risk in a Han Chinese population: a case-control study in Southeast China.

BACKGROUND: We investigated whether BCMO1 variants and dietary patterns are associated with lung cancer risk. METHODS: Case-control study including 1166 lung cancer cases and 1179 frequency matched controls was conducted for three BCMO1 variants (rs6564851, rs12934922, and rs7501331) and four dietary patterns were investigated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: The rs6564851, rs12934922, and rs7501331 were not found to be associated with lung cancer risk (P > 0.05). In multivariable-adjusted models, compared to the lowest quartile of the score on the "fruits and vegetables" pattern, the highest quintile was associated with a 78.4% decreased risk (OR Q4 vs. Q1 = 0.216; 95% CI, 0.164-0.284; P for trend < 0.001). Other patterns were not found the association. The "fruits and vegetables" pattern was associated with a reduced risk of lung cancer with all 3 SNPs irrespective of genotypes (all P for trend< 0.001). The association for the "Frugal" pattern was associated with increased risk of lung cancer among smokers (P for interaction = 0.005). The protective effects of the "cereals/wheat and meat" pattern was more evident for squamous cell carcinoma and other histological type. CONCLUSIONS: We did not observe associations of BCMO1 variants and lung cancer. Diets rich in fruits and vegetables may be protective against lung cancer.

The association between human papillomavirus infection and lung cancer: a system review and meta-analysis.

To estimate the global attributable fraction of human papillomavirus (HPV) in lung cancer, we provided updated information through a system review and meta-analysis. We did a literature search on PubMed, Ovid and Web of Science to identify case-control studies and cohort studies that detected HPV in lung carcinomas. We included studies that tested 30 or more cases and were published before Feb 28, 2017. We collected information about gender, smoking status, HPV detection methods, HPV types, materials and clinical features. If it was not possible to abstract the required information directly from the papers, we contacted the authors. A meta-analysis was performed to calculate the pooled effect sizes (OR/RR) with 95% confidence intervals (CI) including subgroup analysis and meta-regression to explore sources of heterogeneity, by Stata 13.0 software. 36 case-control studies, contributing data for 6,980 cases of lung cancer and 7,474 controls from 17 countries and one cohort study with 24,162 exposed and 1,026,986 unexposed from China were included. HPV infection was associated with cancer of lung, pooled OR was 3.64 (95% CI: 2.60-5.08), calculated with the random-effects model. Pooled OR for allogeneic case-control studies, self-matched case-control studies and nested case-control studies were 6.71 (95% CI: 4.07-11.07), 2.59 (95% CI: 1.43-4.69) and 0.92 (95% CI: 0.63-1.36), respectively. Pooled OR for HPV 16 and HPV 18 infection, were 3.14 (95% CI: 2.07-4.76) and 2.25 (95% CI: 1.49-3.40), respectively. We also found that HPV infection may be associated with squamous cell carcinoma, adenocarcinoma and small cell carcinoma. There is evidence that HPV infection, especially HPV 16 and HPV 18 infection, significantly increase the risk of lung cancer. Future research needs to focus attention toward whether an HPV vaccine can effectively reduce the incidence of lung cancer.

The relationship of lung cancer with menstrual and reproductive factors may be influenced by passive smoking, cooking oil fumes, and tea intake: A case-control study in Chinese women.

The aim of this study was to investigate the association of menstrual and reproductive factors with risk of lung cancer in women. Potential etiological clues related to lung cancer in women are identified to inform preventive strategies.Case-control study of 477 newly diagnosed women with lung cancer and 479 age-matched (±2 years) controls. Data on menstrual and reproductive factors and history of oral contraceptive use were obtained on personal interviews using a structured questionnaire. Risk factors were analyzed by unconditional logistic regression analysis.Maternal age ≥25 years at first birth appeared to protect against female lung cancer [odds ratios (ORs): 0.511, 95% confidence interval (CI), 0.376-0.693]. Age at menopause > 50 years and use of contraceptives was associated with an increased risk of lung cancer in women (OR: 1.471, 95% CI, 1.021-2.119 and OR: 1.844, 95% CI: 1.111-3.061, respectively). Age ≥13 years at menarche was associated with a decreased risk of lung adenocarcinoma (OR: 0.563, 95% CI, 0.317-0.997). There was significant heterogeneity in the levels of cooking oil fume (COF) exposure (Pheterogeneity = .015). Higher levels of exposure to passive smoking, COF, and lack of tea intake were associated with an increased risk of lung cancer.Menstrual and reproductive factors are considered to play a role in the development of lung cancer in women. Exposure to passive smoking, COF, and lack of tea intake appeared to significantly modify the relationship.

A case-control study of the association between self-reported occupational and recreational physical activity and lung cancer.

This case-control study with a Fujian population investigated whether self-reported occupational and recreational physical activity may be associated with lung cancer.The population comprised 1622 patients with newly diagnosed primary lung cancer and 1622 age- and gender-matched healthy controls.High-intensity occupational physical activity was associated with significantly higher risk of lung cancer (OR = 1.354, 95% CI: 1.068-1.717), especially nonsmall cell lung carcinoma (OR = 1.384, 95% CI: 1.087-1.762). Moderate or low intensity recreational physical activity was associated with reduced risk of lung cancer. The protective effect of recreational physical activity was observed in current or former smokers, but not never-smokers, and in subjects with normal or high BMI, but not low BMI, as well as people without a history of chronic lung disease. The frequency of recreational physical activity was associated with a linear reduction in the risk of lung cancer (P < .001), and also specifically nonsmall cell lung cancer (P < .001).Occupational and recreational physical activity was associated with different effects on the risk of lung cancer in a Fujian population. While recreational physical activity was associated with decreased risk of lung cancer, occupational physical activity was associated with increased risk of lung cancer.

[Association of Indoor Air Pollution, Single Nucleotide Polymorphism of HIF-1α Gene with Susceptibility to Lung Cancer in Han Population in Fujian Province].

BACKGROUND: Hypoxia inducible factor-1α (HIF-1α) is associated with the progression and metastasis of lung cancer. There are, however, few studies on the relationship between the single nucleotide polymorphisms of HIF-1α and susceptibility to lung cancer. Therefore, we aimed to investigate the relationship between indoor air pollution, HIF-1α rs2057482, and the susceptibility to primary lung cancer of the Fujian Han population. METHODS: The present study is a hospital-based case-control study. We recruited 1,096 lung cancer and 1,110 controls that were admitted to the Department of Thoracic Surgery of the First Affiliated Hospital and Union Hospital of Fujian Medical University and Fuzhou General Hospital of Nanjing Military Region from January 2006 to December 2012. The primary lung cancer cases were identified via pathological methods. Both case and control groups received questionnaires. Genotyping of HIF-1α gene rs2057482 locus polymorphism in all subjects were analyzed by MALDI-TOF-MS technique. RESULTS: Individuals who carried the T-genotype of HIF-1α rs2057482 were more susceptible to small cell carcinoma (odds ratio of 1.725, 95%CI: 1.047-2.842). After adjusting for general and lung cancer-related factors, we found that in the co-dominant genetic model, rs2057482 TT carriers were 2.195 times more likely to develop lung cancer than CC carriers (95%CI: 1.038-4.463) in the population that were exposed to passive smoking. In the dominant genetic model, the risk of lung cancer was 1.911 times (95%CI: 1.121-3.258) that in the carriers of the rs2057482 T allele with a family history of cancer. In the recessive genetic model, rs2057482 TT carriers had a 0.159-fold increased risk of lung cancer (95%CI: 0.028-0.920) than TC+CC carriers in people with a history of lung disease. In the additive genetic model, the risk of lung cancer in rs2057482 TC+TT carriers was 1.542 times (95%CI: 1.107-2.340) that in the CC family of people with a family history of cancer. CONCLUSIONS: HIF-1α rs2057482 may be associated with lung cancer susceptibility.
.

[Explore the influence factors on primary lung cancer in Fujian province Han population under the use of generalized linear model].

The purpose of this study was to use the data on lung cancer in Han Chinese in Fujian province to explore the value of a generalized, linear model and to investigate the impact related to environment factors on lung cancer as well as the independent and interaction effects on the development of lung cancer. SAS 9.2 was used to build a generalized linear model to evaluate the influence factors and interaction of lung cancer on both smokers and non-smokers. Results showed that the relationship of the factors was multiplied. Under the logistic regression analysis, seven risk factors and nine risk factors were noticed in smokers or in non-smokers, respectively. Heavy smokers and lung diseases appeared a positive multiplying effect on smokers while passive smoking and fresh fruits showed positive multiplying effects on non-smokers. The generalized linear models could filter suitable models thus facilitating further research on the interaction between the two. It seemed easy to carry on the comprehensive and rational analysis on related epidemiological data.