Significance of Gastrokine-1 Polymorphism Rs4254535 as a Prognostic Marker and its Association with Clinical Characteristics in Chinese Lung Cancer Patients.

Background: The single nucleotide polymorphism (SNP) of Gastrokine-1 (GKN1) is associated with lung cancer but its association with prognosis is not clear. Methods: Genomic DNA was extracted from the blood samples of 888 patients with lung cancer. The association between GKN1 polymorphism rs4254535 and prognostic was analyzed by the Kaplan-Meier (KM) method, Log-rank test, and Cox proportional hazards model. Results: In females and patients diagnosed with late-stage lung cancer, the CC genotype (CC vs TT, adjusted odds ratio [HR] = 0.57, 95% Confidence Interval [CI]: 0.33-0.99, P = 0.045; HR = 0.66, 95% CI: 0.48-0.92, P = 0.014) and recessive CC genotype (CC vs TT + TC, HR = 0.55, 95% CI: 0.32-0.94, P = 0.028; HR = 0.64, 95% CI: 0.47-0.89, P = 0.006) of rs4254535 conferred a better prognosis, compared with the TT and TT + TC genotype. Rs4254535 dominate TC + CC genotype, recessive CC genotype, and C allele who were adenocarcinoma patients had a significantly better prognosis. The recessive CC genotype of non-smoking patients has a better prognosis, compared to the TT + TC genotype. Additionally, in the dominant TT + TC genotype and C allele, no family history patients had a significantly better prognosis, compared to the TT genotype. Conclusion: For lung cancer patients, GKN1 polymorphism rs4254535 may be a protective genetic marker and predicts the prognosis of lung cancer patients.

Whole-exome and targeted gene sequencing of large-cell lung carcinoma reveals recurrent mutations in the PI3K pathway.

BACKGROUND: Large cell lung carcinoma (LCLC) is an exceptionally aggressive disease with a poor prognosis. At present, little is known about the molecular pathology of LCLC. METHODS: Ultra-deep sequencing of cancer-related genes and exome sequencing were used to detect the LCLC mutational in 118 tumor-normal pairs. The cell function test was employed to confirm the potential carcinogenic mutation of PI3K pathway. RESULTS: The mutation pattern is determined by the predominance of A > C mutations. Genes with a significant non-silent mutation frequency (FDR) < 0.05) include TP53 (47.5%), EGFR (13.6%) and PTEN (12.1%). Moreover, PI3K signaling (including EGFR, FGRG4, ITGA1, ITGA5, and ITGA2B) is the most mutated pathway, influencing 61.9% (73/118) of the LCLC samples. The cell function test confirmed that the potential carcinogenic mutation of PI3K pathway had a more malignant cell function phenotype. Multivariate analysis further revealed that patients with the PI3K signaling pathway mutations have a poor prognosis (P = 0.007). CONCLUSIONS: These results initially identified frequent mutation of PI3K signaling pathways in LCLC and indicate potential targets for the treatment of this fatal type of LCLC.

Research Progress in Elucidating the Mechanisms Underlying Resveratrol Action on Lung Cancer.

Resveratrol has several functions, including protection of the heart and nervous system and exerts antidiabetic, anti-inflammatory, anti-aging, and antitumor effects. It is reported to impede the occurrence and development of tumors in cancer cell lines, animal models, and clinical studies. In vitro and in vivo experiments show that it exerts preventive or adjuvant therapeutic effects in pancreatic, colorectal, prostate, liver, and lung cancers. Mechanistic research reports show that resveratrol can induce tumor cell apoptosis and autophagy, inhibit cell cycle and angiogenesis, regulate nuclear factors and cyclooxygenase signal transduction pathways, and inhibit carcinogens' metabolic activation and alter tumor-related expression patterns; anti-oxidation affects tumor cell proliferation, metastasis, and apoptosis. However, the exact mechanism underlying its action remains unclear. This review highlights multiple aspects of the biological impacts and mechanisms underlying resveratrol action on the occurrence and development of lung cancer.

Prognostic value of GPC5 polymorphism rs2352028 and clinical characteristics in Chinese lung cancer patients.

Background: GPC5 rs2352028 is associated with the risk of lung cancer, but its relationship with lung cancer prognosis is unclear. Materials & methods: The authors collected blood samples from 888 patients with lung cancer and used a Cox proportional hazards model to analyze the association between prognosis and GPC5 polymorphism rs2352028. Results: GPC5 rs2352028 C > T was associated with a better prognosis. Patients with CT genotype had longer overall survival than those with CC genotype. Additionally, older and early-stage patients with CT + TT genotype had a lower risk of death than those with CC genotype. Conclusion: GPC5 rs2352028 C > T may play a protective role in patients with lung cancer and GPC5 rs2352028 may be a potential genetic marker for lung cancer prognosis.

Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most prevalent forms of lung cancer. Competitive endogenous RNA (ceRNA) plays an important role in the pathogenesis of lung cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumour suppressor genes in LUAD. The present study aimed to identify a novel PTEN-associated-ceRNA regulatory network and identify potential prognostic markers associated with LUAD. Transcriptome sequencing profiles of 533 patients with LUAD were obtained from TCGA database, and differentially expressed genes (DEGs) were screened in LUAD samples with PTEN high- (PTENhigh) and low- (PTENlow) expression. Eventually, an important PTEN-related marker was identified, namely, the LINC00460/miR-150-3p axis. Furthermore, the predicted target genes (EME1/HNRNPAB/PLAUR/SEMA3A) were closely related to overall survival and prognosis. The LINC00460/miR-150-3p axis was identified as a clinical prognostic factor through Cox regression analysis. Methylation analyses suggested that abnormal regulation of the predicted target genes might be caused by hypomethylation. Furthermore, immune infiltration analysis showed that the LINC00460/miR-150-3p axis could alter the levels of immune infiltration in the tumour immune microenvironment, and promote the clinical progression of LUAD. To specifically induce PTEN deletion in the lungs, we constructed an STP mouse model (SFTPC-rtTA/tetO-cre/Ptenflox/+). Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy.

Prediction of lung cancer risk in Chinese population with genetic-environment factor using extreme gradient boosting.

BACKGROUND: Detecting early-stage lung cancer is critical to reduce the lung cancer mortality rate; however, existing models based on germline variants perform poorly, and new models are needed. This study aimed to use extreme gradient boosting to develop a predictive model for the early diagnosis of lung cancer in a multicenter case-control study. MATERIALS AND METHODS: A total of 974 cases and 1005 controls in Shanghai and Taizhou were recruited, and 61 single nucleotide polymorphisms (SNPs) were genotyped. Multivariate logistic regression was used to calculate the association between signal SNPs and lung cancer risk. Logistic regression (LR) and extreme gradient boosting (XGBoost) algorithms, a large-scale machine learning algorithm, were adopted to build the lung cancer risk model. In both models, 10-fold cross-validation was performed, and model predictive performance was evaluated by the area under the curve (AUC). RESULTS: After FDR adjustment, TYMS rs3819102 and BAG6 rs1077393 were significantly associated with lung cancer risk (p < 0.05). For lung cancer risk prediction, the model predicted only with epidemiology attained an AUC of 0.703 for LR and 0.744 for XGBoost. Compared with the LR model predicted only with epidemiology, further adding SNPs and applying XGBoost increased the AUC to 0.759 (p < 0.001) in the XGBoost model. BAG6 rs1077393 was the most important predictor among all SNPs in the lung cancer prediction XGBoost model, followed by TERT rs2735845 and CAMKK1 rs7214723. Further stratification in lung adenocarcinoma (ADC) showed a significantly elevated performance from 0.639 to 0.699 (p = 0.009) when applying XGBoost and adding SNPs to the model, while the best model for lung squamous cell carcinoma (SCC) prediction was the LR model predicted with epidemiology and SNPs (AUC = 0.833), compared with the XGBoost model (AUC = 0.816). CONCLUSION: Our lung cancer risk prediction models in the Chinese population have a strong predictive ability, especially for SCC. Adding SNPs and applying the XGBoost algorithm to the epidemiologic-based logistic regression risk prediction model significantly improves model performance.

Prognosis of lung cancer with simple brain metastasis patients and establishment of survival prediction models: a study based on real events.

OBJECTIVES: The aim of this study was to explore risk factors for the prognosis of lung cancer with simple brain metastasis (LCSBM) patients and to establish a prognostic predictive nomogram for LCSBM patients. MATERIALS AND METHODS: Three thousand eight hundred and six cases of LCSBM were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 using SEER Stat 8.3.5. Lung cancer patients only had brain metastasis with no other organ metastasis were defined as LCSBM patients. Prognostic factors of LCSBM were analyzed with log-rank method and Cox proportional hazards model. Independent risk and protective prognostic factors were used to construct nomogram with accelerated failure time model. C-index was used to evaluate the prediction effect of nomogram. RESULTS AND CONCLUSION: The younger patients (18-65 years old) accounted for 54.41%, while patients aged over 65 accounted for 45.59%.The ratio of male: female was 1:1. Lung cancer in the main bronchus, upper lobe, middle lobe and lower lobe were accounted for 4.91%, 62.80%, 4.47% and 27.82% respectively; and adenocarcinoma accounted for 57.83% of all lung cancer types. The overall median survival time was 12.2 months. Survival rates for 1-, 3- and 5-years were 28.2%, 8.7% and 4.7% respectively. We found female (HR = 0.81, 95% CI 0.75-0.87), the married (HR = 0.80; 95% CI 0.75-0.86), the White (HR = 0.90, 95% CI 0.84-0.95) and primary site (HR = 0.45, 95% CI 0.39-0.52) were independent protective factors while higher age (HR = 1.51, 95% CI 1.40-1.62), advanced grade (HR = 1.19, 95% CI 1.12-1.25) and advanced T stage (HR = 1.09, 95% CI 1.05-1.13) were independent risk prognostic factors affecting the survival of LCSBM patients. We constructed the nomogram with above independent factors, and the C-index value was 0.634 (95% CI 0.622-0.646). We developed a nomogram with seven significant LCSBM independent prognostic factors to provide prognosis prediction.

Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring.

Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.

MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer.

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.

Elevated Stratifin promotes cisplatin-based chemotherapy failure and poor prognosis in non-small cell lung cancer.

Drug resistance is a key factor in the treatment failure of clinical non-small cell lung cancer (NSCLC) patients after adjuvant chemotherapy. Here, our results provide the first evidence that eukaryotic translation initiation factor 2b subunit delta (EIF2B4)-Stratifin (SFN) fusion and increased SFN expression are associated with chemotherapy tolerance and activation of the phosphatidylinositol 3 kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) signaling pathway in NSCLC patients, suggesting that SFN might have potential prognostic value as a tumor biomarker for the prognosis of patients with NSCLC.

MicroRNA-499 serves as a sensitizer for lung cancer cells to radiotherapy by inhibition of CK2α-mediated phosphorylation of p65.

The present study aimed to define the tumor-suppressive role of microRNA-499 (miR-499) in lung cancer cells and its underlying mechanism. First, qRT-PCR analysis revealed poor expression of miR-499 in clinical samples and cell lines of lung cancer. Next, we performed loss- and gain-of-function experiments for the expression of miR-499 in lung cancer cells exposed to irradiation (IR) to determine the effect of miR-499 expression on cell viability and apoptosis as well as tumor growth. Results showed that overexpression of miR-499 inhibited cell viability, enhanced the radiosensitivity of lung cancer cells, and promoted cell apoptosis under IR. Furthermore, CK2α was verified to be a target of miR-499, and miR-499 was identified to repress p65 phosphorylation by downregulating CK2α expression, which ultimately diminished the survival rate of lung cancer cells under IR. Collectively, the key findings of the study illustrate the tumor-inhibiting function of miR-499 and confirmed that miR-499-mediated CK2α inhibition and altered p65 phosphorylation enhances the sensitivity of lung cancer cells to IR.

microRNA-320b suppresses HNF4G and IGF2BP2 expression to inhibit angiogenesis and tumor growth of lung cancer.

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.

Systematic analysis using a bioinformatics strategy identifies SFTA1P and LINC00519 as potential prognostic biomarkers for lung squamous cell carcinoma.

Lung cancer has high incidence and mortality rates, in which lung squamous cell carcinoma (LUSC) is a primary type of non-small cell lung carcinoma (NSCLC). The aim of our study was to discover long non-coding RNAs (lncRNAs) associated with diagnose and prognosis for LUSC. RNA sequencing data obtained from LUSC samples were extracted from The Cancer Genome Atlas database (TCGA). Two prognosis-associated lncRNAs (including SFTA1P and LINC00519) were selected from LUSC samples, and the expression levels were also verified to be associated abnormal in LUSC clinical samples. Our findings demonstrate that lncRNAs SFTA1P and LINC00519 exert important functions in human LUSC and may serve as new targets for LUSC diagnosis and therapy.

Identified GNGT1 and NMU as Combined Diagnosis Biomarker of Non-Small-Cell Lung Cancer Utilizing Bioinformatics and Logistic Regression.

Non-small-cell lung cancer (NSCLC) is one of the most devastating diseases worldwide. The study is aimed at identifying reliable prognostic biomarkers and to improve understanding of cancer initiation and progression mechanisms. RNA-Seq data were downloaded from The Cancer Genome Atlas (TCGA) database. Subsequently, comprehensive bioinformatics analysis incorporating gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the protein-protein interaction (PPI) network was conducted to identify differentially expressed genes (DEGs) closely associated with NSCLC. Eight hub genes were screened out using Molecular Complex Detection (MCODE) and cytoHubba. The prognostic and diagnostic values of the hub genes were further confirmed by survival analysis and receiver operating characteristic (ROC) curve analysis. Hub genes were validated by other datasets, such as the Oncomine, Human Protein Atlas, and cBioPortal databases. Ultimately, logistic regression analysis was conducted to evaluate the diagnostic potential of the two identified biomarkers. Screening removed 1,411 DEGs, including 1,362 upregulated and 49 downregulated genes. Pathway enrichment analysis of the DEGs examined the Ras signaling pathway, alcoholism, and other factors. Ultimately, eight prioritized genes (GNGT1, GNG4, NMU, GCG, TAC1, GAST, GCGR1, and NPSR1) were identified as hub genes. High hub gene expression was significantly associated with worse overall survival in patients with NSCLC. The ROC curves showed that these hub genes had diagnostic value. The mRNA expressions of GNGT1 and NMU were low in the Oncomine database. Their protein expressions and genetic alterations were also revealed. Finally, logistic regression analysis indicated that combining the two biomarkers substantially improved the ability to discriminate NSCLC. GNGT1 and NMU identified in the current study may empower further discovery of the molecular mechanisms underlying NSCLC's initiation and progression.

Effect of ERCC2 rs13181 and rs1799793 polymorphisms and environmental factors on the prognosis of patients with lung cancer.

PURPOSE: The 5-year survival rate of patients with lung cancer in China is < 20%, and predicting their prognosis is difficult. Here, we investigated the association between two common non-synonymous single-nucleotide polymorphisms (SNPs) in the excision repair cross-complementing 2 (ERCC2) genes (rs13181 and rs1799793) and the prognosis of patients with lung cancer. METHODS: Genomic DNA was extracted from the blood samples of 839 patients with lung cancer and genotyped using the SNPscan technique. The association between patient prognosis and the ERCC2 genotype was analyzed using a multivariate Cox proportional hazards model adjusted for multiple potential confounders. RESULTS: The presence of ERCC2 rs13181 T>G significantly increased the risk of death (adjust hazard ratio (HR) = 1.29, 95% CI: 1.06-1.56, P = 0.009). Patients with the rs13181 TG genotype (adjust HR = 1.34, 95% CI: 1.08-1.65, P = 0.007) and rs13181 dominant mode TG+GG (adjust HR = 1.33, 95% CI: 1.08-1.63, P = 0.007) had significantly worse overall survival. Moreover, stratified analyses showed that patients with the TG and TG+GG rs13181 genotypes who were male, elderly (≥60 years), had a history of smoking, or without family history of malignant tumors had a significantly increased risk of death. In patients with adenocarcinoma lung cancer (ADC), the rs1799793 genotype CT (adjust HR = 1.49, 95% CI: 1.06-2.09, P = 0.023) and dominant model CT+TT (adjust HR = 1.45, 95% CI = 1.04-2.02, P = 0.027) were associated with an increased risk of death. CONCLUSION: ERCC2 rs13181 and rs1799793 SNPs may be significant prognostic factors for the risk of death among patients with lung cancer.

Polymorphism rs3819102 in thymidylate synthase and environmental factors: effects on lung cancer in Chinese population.

PURPOSE: Lung cancer is the leading cause of cancer death worldwide, and the predominant risk factor for its development is smoking. Thymidylate synthase (TYMS) is a key enzyme in DNA synthesis that catalyzes the conversion of deoxyuridine monophosphate to dTMP. Rs931794, a single nucleotide polymorphism located in the TYMS gene, was suggested to be associated with cancer risk. METHODS: To analyze the interaction between rs3819102 and environmental factors on the risk of lung cancer in a Chinese population, single nucleotide polymorphismscan was used to genotype this polymorphism in 974 lung cancer cases and 1005 control subjects. RESULTS: The frequencies of TT, CT, and CC genotypes of TYMS rs3819102 were 61.8%, 32.9%, and 5.3% in controls, and 53.8%, 38.4%, and 7.8% in cases, respectively. Compared with the TT genotype, the CT (odds ratio [OR], 1.380; 95% confidence interval [CI], 1.131-1.683), and CC (OR, 1.786; 95% CI, 1.213-2.644) genotypes were associated with an increased risk of lung cancer after adjustment for age, gender, smoking status, and family history. The C allele of rs3819102 is the risk allele for lung carcinogenesis in a dominant model (OR, 1.435; 95% CI, 1.188-1.735). In a stratified analysis, the risk effects of both the CT and CC genotypes of rs3819102 were more evident in subgroups of smokers and people without a family history of cancer. CONCLUSION: The rs3819102 polymorphism in TYMS might increase susceptibility to environmental factors and contribute to the risk of lung cancer. The C allele is a risk allele in lung carcinogenesis.

High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1.

Increasing evidence supports that microRNA (miRNA)-mediated gene regulation plays a significant functional role in cancer progression. To investigate the expression and clinical significance of ITGB1 in non small cell lung cancer (NSCLC), the expression levels of ITGB1 in NSCLC tissues and human normal lung tissues were analyzed in silico using genes microarray, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results showed that ITGB1 was upregulated in NSCLC tissues when compared with normal lung tissues. Survival analysis based on the qRT-PCR data established that ITGB1 expression was attentively related to the prognosis of NSCLC, and patients with higher ITGB1 expression had shorter overall survival (OS). Moreover, ITGB1 was confirmed to be a direct target of miR-493-5p. Furthermore, concomitant high expression of ITGB1 and low expression of miR-493-5p correlated with a shorter median OS and PFS in NSCLC patients. In conclusion, our results provide the first evidence that ITGB1 is a direct target of miR-493-5p suggesting that ITGB1 and miR-493-5p may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of NSCLC patients.

Consumption of whole grains in relation to mortality from all causes, cardiovascular disease, and diabetes: Dose-response meta-analysis of prospective cohort studies.

BACKGROUND: To investigate the correlation between consumption of whole grains and the risk of all-cause, cardiovascular disease (CVD), and diabetes-specific mortality according to a dose-response meta-analysis of prospective cohort studies. METHODS: Observational cohort studies, which reported associations between whole grains and the risk of death outcomes, were identified by searching articles in the MEDLINE, EMBASE, and the reference lists of relevant articles. The search was up to November 30, 2015. Data extraction was performed by 2 independent investigators, and a consensus was reached with involvement of a third. RESULTS: Ten prospective cohort studies (9 publications) were eligible in this meta-analysis. During follow-up periods ranging from 5.5 to 26 years, there were 92,647 deaths among 782,751 participants. Overall, a diet containing greater amounts of whole grains may be associated with a lower risk of all-cause, CVD-, and coronary heart disease (CHD)-specific mortality. The summary relative risks (RRs) were 0.93 (95% confidence intervals [CIs]: 0.91-0.95; Pheterogeneity < 0.001) for all-cause mortality, 0.95 (95% CIs: 0.92-0.98; Pheterogeneity < 0.001) for CVD-specific mortality, and 0.92 (95% CIs: 0.88-0.97; Pheterogeneity < 0.001) for CHD-specific mortality for an increment of 1 serving (30 g) a day of whole grain intake. The combined estimates were robust across subgroup and sensitivity analyses. Higher consumption of whole grains was not appreciably associated with risk of mortality from stroke and diabetes. CONCLUSION: Evidence from observational cohort studies indicates inverse associations of intake of whole grains with risk of mortality from all-cause, CVD, and CHD. However, no associations with risk of deaths from stroke and diabetes were observed.

Decreased expression of microRNA-320a promotes proliferation and invasion of non-small cell lung cancer cells by increasing VDAC1 expression.

Accumulating evidence indicates that Voltage Dependent Anion Channel 1 (VDAC1) correlates with the initiation and progression of non-small cell lung cancer (NSCLC). However, the regulatory mechanism of VDAC1 in NSCLC remains unclear. Previous studies have reported that expression of miR-320a was decreased in human primary squamous cell lung carcinoma, which prompted us to investigate whether there is a functional link between decreased miR-320a and a high expression of VDAC1. In the present report, using computational analysis, we first show that miR-320a has a potential binding site on VDAC1 mRNA, and expression of miR-320a was decreased in NSCLC cell lines. Using gain-of-function and rescue experiments, we demonstrate that VDAC1 is a direct target of miR-320a in NSCLC cells, and miR-320a inhibits VDAC1 expression in NSCLC cells. Further we show that MiR-320a was significantly decreased in NSCLC tissues compared with adjacent non-tumor tissues, and MiR-320a level is negatively correlated with VDAC1 in NSCLC tissues by Pearson's correlation coefficient analysis. Moreover, using cellular ATP assay, we found that suppression of VDAC1 expression may inhibit cell proliferation and invasion of NSCLC by decreasing cell energy and metabolism. Importantly, we showed that ectopic overexpression of miR-320a blocked tumor cell proliferation and invasion, both in vitro and in vivo, through inhibiting VDAC1. Our results suggest that reduced expression of miR-320a facilitates the development of NSCLCs by increasing VDAC1 expression. We identified a novel regulatory mechanism between miR-320a and VDAC1, and miR-320a may serve as a tumor suppressor gene and a promising therapeutic target of NSCLCs.

Poultry and fish intake and risk of esophageal cancer: A meta-analysis of observational studies.

AIM: Mixed results regarding the association between white meat (including poultry and fish) intake and the risk of esophageal cancer (EC) have been reported. We performed a meta-analysis to provide a quantitative assessment of this association. METHOD(S): Relevant studies were identified in MEDLINE until December 31, 2012. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. RESULTS: A total of 20 articles, including 3990 cases with EC, were included in this meta-analysis. Compared to individuals with the lowest level of fish intake, individuals with the highest fish intake were found to have reduced risk of EC (SRRs = 0.69; 95% CIs: 0.57-0.85), while poultry intake was not associated with EC (SRRs = 0.83; 95% CIs: 0.62-1.12). Total fish consumption is associated with reduced esophageal squamous cell carcinoma (ESCC) risk, while poultry consumption was not associated with ESCC risk. Additionally, neither poultry nor fish consumption was associated with esophageal adenocarcinoma risk. CONCLUSION(S): Our results suggest that fish consumption may have a potential role in EC prevention, while poultry intake has no effect. However, because the majority of data was from case-control studies, further well-designed prospective studies are warranted.