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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.

// Xue Fang 1, 2, 4 , Xuelian Li 1, 2 , Zhihua Yin 1, 2 , Lingzi Xia 1, 2 , Xiaowei Quan 1, 2 , Yuxia Zhao 3 and Baosen Zhou 1, 2 1 Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China 2 Liaoning Provincial Department of Education, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning, China 3 Department of Radiotherapy, The Fourth Affiliated Hospital of China Medical University, Shenyang, China 4 Department of Epidemiology, School of Public Health, Shenyang Medical College, Shenyang, China Correspondence to: Baosen Zhou, email: bszhou@mail.cmu.edu.cn Keywords: single nucleotide polymorphism, lung cancer, CAV1, microRNA Received: April 27, 2017 Accepted: September 05, 2017 Published: October 09, 2017 ABSTRACT 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, it’s 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.

// Xu Feng 1, 2 , Xue Fang 1, 3 , Lingzi Xia 1, 3 , Yangwu Ren 1, 3 , Xuelian Li 1, 3 , Xiaowei Quan 1, 3 and Baosen Zhou 1, 3 1 Department of Epidemiology, School of Public Health, China Medical University, Liaoning, China 2 Department of Health Statistics, School of Public Health, Shenyang Medical College, Liaoning, China 3 Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Department of Education, Liaoning, China Correspondence to: Baosen Zhou, email: bszhou@mail.cmu.edu.cn Keywords: PPP1R13L, CD3EAP, single nucleotide polymorphism, non-small cell lung cancer Received: April 11, 2017 Accepted: July 19, 2017 Published: August 12, 2017 ABSTRACT 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.

Purpose: This study tried to explore whether members of miR-92a family contribute to early diagnosis and prognosis for human cancers and how they work. Methods: Integrated meta-analysis retrieved from public repositories was employed to assess the clinical roles of the miR-92a family for cancer diagnosis and prognosis. Expression level of miR-92a was detected by the TCGA database and was confirmed by non-small-cell lung cancer (NSCLC) tissues. Targets of miR-92a were predicted using starbase, and validated by dual luciferase assay. Correlation between miR-92a and the target gene was assessed by linkedOmics while expression of the target gene and its role in cancer prognosis were analyzed with UALCAN and Gepia. Results: We recognized the miR-92a family could serve as a potential diagnostic biomarker with a pooled sensitivity of 0.85 [0.81-0.88] and specificity of 0.86 [0.83-0.90]. The overall hazard ratio (HR) was 2.26 [95% CI: 1.70-3.00] for high expression groups compared to low expression groups. Expression of miR-92a was identified to be upregulated in NSCLC, especially in lung squamous cell carcinoma (LUSC). Results from starbase and dual luciferase assay indicated the regulator of G-protein signaling 3 (RGS3) was a direct target of miR-92a. Statistical negative correlation was found for the expression of miR-92a and RGS3. In addition, expression of RGS3 was downregulated in NSCLC and patients with the high expression had a poor prognosis (HR = 1.3) for LUSC patients. However, results were to the contrary for lung adenocarcinoma (HR = 0.7). Conclusion: This study revealed that miR-92a family could be ideal biomarkers for cancer diagnosis and prognosis, which might function through targeting RGS3.

Lung cancer is known to cause high mortality and morbidity. The study aimed to explore the association between rs3733845 and rs3733846 polymorphisms in the promoter region of miR-143/145 and the risk of lung cancer among 575 nonsmoking cases and 575 cancer-free controls in a Chinese female population. We genotyped two single nucleotide polymorphisms (SNPs) in the promoter region of miR-143/145 in 575 cases and 575 controls using TaqMan allelic discrimination method. Logistic regression analysis was conducted to assess the association between polymorphisms in the promoter of miR-143/miR-145 and risk of lung cancer females. Crossover analysis was used to explore the interaction between the two SNPs and environmental risk factors (cooking oil fume exposure and passive smoking exposure). The results showed that both rs3733845 and rs3733846 polymorphisms were associated with an increased lung adenocarcinoma risk in dominant model (adjusted odds ratio [OR] = 1.329, 95% confidence intervals [CIs] = 1.026-1.723

// Xue Fang 1, 2 , Zhihua Yin 1, 2 , Xuelian Li 1, 2 , Lingzi Xia 1, 2 , Xiaowei Quan 1, 2 , Yuxia Zhao 3 , Baosen Zhou 1, 2 1 Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China 2 Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Department of Education, Liaoning, China 3 Department of Radiotherapy, The Fourth Affiliated Hospital of China Medical University, Shenyang, China Correspondence to: Baosen Zhou, email: bszhou@mail.cmu.edu.cn Keywords: differentially expressed genes, functional single nucleotide polymorphism, non-small cell lung cancer, risk, survival Received: December 02, 2016 Accepted: January 11, 2017 Published: January 27, 2017 ABSTRACT 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.

Objective: The clinical use of intermittent infusion of vancomycin (IIV) and continuous infusion of vancomycin (CIV) is controversial. The aim of this study was to assess the effectiveness and safety of IIV and CIV by using a meta-analysis for cohort studies and randomized controlled trials. Methods: We compared the probabilities of target attainment (PTA) for the measured concentration (Cm) ≥the target concentration (Ct), the PTA for the area under the drug concentration curve/minimal inhibitory concentration (AUC/MIC) ≥400, the duration of treatment, nephrotoxicity, and overall mortality after vancomycin treatment as reported in PubMed, Embase, Cochrane, and Web of Science. Results: A total of 14 studies with 1640 patients were included in the meta-analysis. For IIV, the PTA of Cm ≥ Ct (RR = 0.72, 95% CI = 0.60–0.88), and nephrotoxicity (RR = 1.70, 95% CI = 1.34–2.14) were significantly different from those of CIV. The treatment duration (SMD = 0.08, 95% CI = −0.08–0.25), the PTA of AUC/MIC ≥ 400 (RR = 0.84, 95% CI = 0.70–1.00) and mortality (RR = 0.94, 95% CI = 0.72–1.25) were not significantly different from those of CIV. Conclusions: The results showed that CIV was easier to achieve Ct and safer than IIV. Additional randomized controlled trials focusing on the concentration of vancomycin are needed for further analysis. Keywords: Vancomycin, Intermittent, Continuous, Effectiveness, Safety

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.

(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.

// Chang Zheng 1, 2 , Xuelian Li 1, 2 , Lingzi Xia 1, 2 , Xue Fang 1, 2 , Xiaowei Quan 1, 2 , Zhihua Yin 1, 2 , Yuxia Zhao 3 and Baosen Zhou 1, 2 1 Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China 2 Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Department of Education, Liaoning, China 3 Department of Radiotherapy, The Fourth Affiliated Hospital of China Medical University, Shenyang, China Correspondence to: Baosen Zhou, email: bszhou@mail.cmu.edu.cn Keywords: SNP, miRNA, NSCLC, susceptibility, prognosis Received: January 17, 2017 Accepted: March 21, 2017 Published: April 11, 2017 ABSTRACT 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

// Xiaowei Quan 1, 2 , Zhihua Yin 1, 2 , Xue Fang 1, 2 , Baosen Zhou 1, 2 1 Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China 2 Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Department of Education, Liaoning, China Correspondence to: Baosen Zhou, email: bszhou@cmu.edu.cn Keywords: Notch1, single nucleotide polymorphisms, lung cancer, small cell lung cancer, non-smoking females Received: October 19, 2016 Accepted: March 01, 2017 Published: March 10, 2017 ABSTRACT Lung cancer is one of the most common cancers and the main cause of cancer-related deaths. Notch1 might play a part in tumorigenesis of lung cancer. Here we explored the relationship of three SNPs (rs3124599, rs3124607 and rs3124594) in Notch1 with the risk and the survival of lung cancer in non-smoking females, including 556 cases and 395 controls. Chi-square tests, logistic regression analysis and crossover analysis were conducted to estimate the association between SNPs and the risk of lung cancer and the interaction between SNPs and environmental exposure. Survival analysis was conducted to explore the association between SNPs and survival of lung cancer. The results demonstrated that the polymorphism of rs3124599 was associated with the susceptibility of lung cancer in recessive model (AA+AG vs. GG). Compared to the those with AA or AG genotype, individuals with GG genotype had a 1.562-fold increased risk of lung cancer ( P = 0.023, OR = 1.562, 95% CI = 1.062-2.297). In stratified analysis, the GG genotype of rs3124599 would increase the risk of small cell lung cancer (SCLC) ( P = 0.011, OR = 2.167, 95% CI = 1.193-3.396). However, no significant interaction between rs3124599 and cooking oil fume exposure was observed either in addictive model or multiplicative model. The results of survival analysis showed there was no significant association between SNPs and prognosis of lung cancer ( P = 0.949 for rs3124599, P = 0.508 for rs3124607, P = 0.884 for rs3124594). Our study might indicate that rs312599 in Notch1 may be a novel biomarker for SCLC risk in Chinese non-smoking females