Xuelian Li

Multiple functional SNPs in differentially expressed genes modify risk and survival of non-small cell lung cancer in Chinese female non-smokers

DNA genotype can affect gene expression, and gene expression can influence the onset and progression of diseases. Here we conducted a comprehensive study, we integrated analysis of gene expression profile and single nucleotide polymorphism (SNP) microarray data in order to scan out the critical genetic changes that participate in the onset and development of non-small cell lung cancer (NSCLC). Gene expression profile datasets were downloaded from the GEO database. Firstly, differentially expressed genes (DEGs) between NSCLC samples and adjacent normal samples were identified. Next, by STRING database, protein-protein interaction (PPI) network was constructed. At the same time, hub genes in PPI network were identified. Then, some functional SNPs in hub genes that may affect gene expression have been annotated. Finally, we carried a study to explore the relationship between functional SNPs and NSCLC risk and overall survival in Chinese female non-smokers. A total of 488 DEGs were identified in our study. There are 29 proteins with a higher degree of connectivity in the PPI network, including FOS, IL6 and MMP9. By using database annotation, we got 8 candidate functional SNPs that may affect the expression level of hub proteins. In the case-control study, we found that rs4754-T allele, rs959173-C allele and rs2239144-G allele were the protective allele of NSCLC risk. In dominant model, rs4754-CT+TT genotype were associated with a shorter survival time. In general, our study provides a novel research direction in the field of multi-omic data integration, and helps us find some critical genetic changes in disease.

Single Nucleotide Polymorphisms in HMGB1 Correlate with Lung Cancer Risk in the Northeast Chinese Han Population

Lung cancer is the principal cause of cancer-associated deaths. HMGB1 has been reported to be associated with tumorigenesis. This study aimed to investigate the relationship between rs1412125 and rs1360485 polymorphisms in HMGB1 and the risk and survival of lung cancer. 850 cases and 733 controls were included. Logistic regression analysis and survival analysis were performed to investigate the association between SNPs and the risk and survival of lung cancer. Crossover analysis was used to analyze the interaction between SNPs and tobacco exposure. Results indicated that rs1412125 polymorphism was associated with lung cancer risk, especially with the risk of lung adenocarcinoma and small cell lung cancer. Carriers with CT and CC genotypes had a decreased risk of lung cancer (CT + CC vs.TT: adjusted OR = 0.736, p = 0.004). Similar results were obtained in the stratification analysis for non-smokers and female population. For rs1360485 polymorphism, AG and GG genotypes could decrease the risk of lung adenocarcinoma and female lung cancer by 0.771-fold and 0.789-fold. However, no significant interaction between polymorphisms and tobacco exposure or association between SNPs and the survival of lung cancer was observed. This study indicated polymorphisms in HMGB1 may be a novel biomarker for female lung adenocarcinoma risk.

Polymorphisms of pri-miR-219-1 are associated with the susceptibility and prognosis of non-small cell lung cancer in a Northeast Chinese population

Occurrence and development of non-small cell lung cancer (NSCLC) is a complex process affected both by gene and environment. Single nucleotide polymorphisms (SNPs) in microRNAs’ (miRNAs) biogenesis influenced the expression of mature miRNAs, further had an impact on risk of NSCLC. Our study focused on the correlation between rs213210, rs421446 or rs107822 polymorphisms in pri-miR-219-1 and susceptibility or prognosis of NSCLC in Chinese. A case-control study of 405 new-diagnosis patients and 405 controls was performed. Ten ml venous blood from each subject was collected for genotype test via using TaqMan allelic discrimination methodology and SPSS was performed for statistical analyses. We found that CC genotype in rs213210 (OR=3.462, 95%CI=2.222-5.394, P<0.001) compared with TT genotype and GG genotype in rs107822 (OR=3.553, 95%CI=2.329-5.419, P<0.001) compared with AA genotype showed significantly increased risk of NSCLC. Haplotype analysis showed that pri-miR-219-1 haplotype Crs213210Crs421446Grs107822 was a dangerous haplotype for lung cancer. And polymorphisms in pri-miR-219-1 have showed no relationship with overall survival of NSCLC. Overall, these findings firstly showed that rs213210 and rs107822 could be meaningful as genetic markers for lung cancer risk.Occurrence and development of non-small cell lung cancer (NSCLC) is a complex process affected both by gene and environment. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) biogenesis influenced the expression of mature miRNAs, further had an impact on risk of NSCLC. Our study focused on the correlation between rs213210, rs421446 or rs107822 polymorphisms in pri-miR-219-1 and susceptibility or prognosis of NSCLC in Chinese. A case-control study of 405 new-diagnosis patients and 405 controls was performed. Ten ml venous blood from each subject was collected for genotype test via using TaqMan allelic discrimination methodology and SPSS was performed for statistical analyses. We found that CC genotype in rs213210 (OR=3.462, 95%CI=2.222-5.394, P<0.001) compared with TT genotype and GG genotype in rs107822 (OR=3.553, 95%CI=2.329-5.419, P<0.001) compared with AA genotype showed significantly increased risk of NSCLC. Haplotype analysis showed that pri-miR-219-1 haplotype Crs213210Crs421446Grs107822 was a dangerous haplotype for lung cancer. And polymorphisms in pri-miR-219-1 have showed no relationship with overall survival of NSCLC. Overall, these findings firstly showed that rs213210 and rs107822 could be meaningful as genetic markers for lung cancer risk.

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.

A Meta-Analysis of miR-499 rs3746444 Polymorphism for Cancer Risk of Different Systems: Evidence From 65 Case-Control Studies

MicroRNAs (miRNAs) are a class of endogenous, short and non-coding RNAs that may play important roles in the pathogenesis of tumor. The associations between microRNA-499 rs3746444 polymorphism and cancer risk in different systems remain inconclusive. This article is aimed to obtain more exact estimation of these relationships through a meta-analysis based on 52,456 individuals. We retrieved relevant and eligible studies from Pubmed and Embase database up to January 10, 2018. ORs and 95% CIs were used to estimate the associations between miR-499 polymorphism and cancer susceptibility in different systems. All analyses were performed using the Stata 11.0 software. A total of 65 case-control studies were retrieved using explicit inclusion and exclusion criteria. The study included 23,762 cases and 28,694 controls. Overall cancer analysis showed the association between miR-499 polymorphism and susceptibility to cancer was significant. MicroRNA-499 rs3746444 was found to be significantly associated with increased risk of cancer of the respiratory system (CC vs. TT: OR = 1.575, 95% CI = 1.268–1.955, CC vs. TC+TT: OR = 1.527, 95% CI = 1.232–1.892), digestive system (CC vs. TT: OR = 1.153, 95% CI = 1.027–1.295; TC vs. TT: OR = 1.109, 95% CI = 1.046–1.176; CC+TC vs. TT: OR = 1.112, 95% CI = 1.018–1.216; CC vs. TC+TT: OR = 1.137, 95% CI = 1.016–1.272; C vs. T: OR = 1.112, 95% CI = 1.025–1.206), urinary system (TC vs. TT: OR = 1.307, 95% CI = 1.130–1.512; CC+TC vs. TT: OR = 1.259, 95% CI = 1.097–1.446; C vs. T: OR = 1.132, 95% CI = 1.014–1.264), and gynecological system (C vs. T: OR = 1.169, 95% CI = 1.002–1.364). In the subgroup analysis by ethnicity, the result showed that significant association with an increased cancer risk was found in Asian. Subgroup analysis based on type of tumor was also performed, miR-499 rs3746444 is associated with susceptibility of cervical squamous cell carcinoma, lung cancer, prostate cancer, and hepatocellular carcinoma.

Clinically Correlated MicroRNAs in the Diagnosis of Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

(1) Background. Non-small cell lung cancer (NSCLC) has a high mortality rate. MiRNAs have been found to be diagnostic biomarkers for NSCLC. However, controversial results exist. We conducted this meta-analysis to evaluate the diagnostic value of miRNAs for NSCLC. (2) Methods. Databases and reference lists were searched. Pooled sensitivity (SEN), specificity (SPE), and area under the curve (AUC) were applied to examine the general diagnostic efficacy, and subgroup analysis was also performed. (3) Results. Pooled SEN, SPE, and AUC were 85%, 88%, and 0.93, respectively, for 71 studies. Multiple miRNAs (AUC: 0.96) obtained higher diagnostic value than single miRNA (AUC: 0.86), and the same result was found for Caucasian population (AUC: 0.97) when compared with Asian (AUC: 0.91) and Caucasian/African population (AUC: 0.92). MiRNA had higher diagnostic efficacy when participants contained both smokers and nonsmokers (AUC is 0.95 for imbalanced group and 0.91 for balanced group) than when containing only smokers (AUC: 0.90). Meanwhile, AUC was 0.91 for both miR-21 and miR-210. (4) Conclusions. Multiple miRNAs such as miR-21 and miR-210 could be used as diagnostic tools for NSCLC, especially for the Caucasian and nonsmoking NSCLC.

Genetic variation at the microRNA binding site of CAV1 gene is associated with lung cancer susceptibility

Single nucleotide polymorphism (SNP) may influence the genesis and development of cancer in a variety of ways depending on their location. Here we conducted a study in Chinese female non-smokers to investigate the relationship between rs1049337, rs926198 and the risk or survival of lung cancer. Further, we explored whether rs1049337 could alter the binding affinity between the mRNA of CAV1 and the corresponding microRNAs. Finally, we evaluated the relationship between expression level of CAV1 and prognosis of lung cancer. The results showed that the rs1049337-C allele and rs926198-C allele were the protective alleles of lung cancer risk. Haplotype analysis indicated that the C-C haplotype (constructed by rs1049337 and rs926198) was a protective haplotype for lung cancer risk. The result of luciferase reporter assay showed that rs1049337 can affect the binding affinity of CAV1 mRNA to the corresponding microRNAs both in A549 cell line and H1299 cell line. Compared with C allele, T allele had a relatively decreased luciferase activity. Compared with paired normal adjacent tissue or normal lung tissue, lung cancer tissue showed a relatively low level of CAV1. Refer to those patients at early stage of lung cancer, the expression level of CAV1 in patients at late stage of lung cancer was relatively low. In conclusion, the results indicated that rs1049337, its a SNP located at 3′UTR region of CAV1 may affect lung cancer risk by altering the binding affinity between the mRNA of CAV1 and the corresponding microRNAs.

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.

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.

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.