Yujiao Deng

Meta-analysis of programmed cell death 1 polymorphisms with systemic lupus erythematosus risk

The association of polymorphisms in programmed cell death 1 (PDCD1) gene with systemic lupus erythematosus (SLE) risk is inconsistent across different studies. This meta-analysis is aimed to provide reliable evidence to the association of five common PDCD1 polymorphisms (PD1.1, PD1.2, PD1.3, PD1.5 and PD1.6) with SLE risk. A total of 28 studies with 4,344 SLE cases and 5,474 healthy controls were included in this meta-analysis. PD1.3 polymorphism was significantly associated with SLE in the overall population (A vs. G: OR = 1.35, 95% CI = 1.12-1.63; GA vs.GG: OR = 1.41, 95% CI = 1.12-1.76; AA+GA vs. GG: OR = 1.41, 95% CI = 1.13-1.7). In the stratified analyses based on ethnicity, we found a significant association in Caucasians and in Mexicans. In the subgroup analyses by gender, a significant association was found between PD1.3 polymorphism and SLE risk in males. The results also suggested an association between the PD1.6 polymorphism and decreased SLE risk (A vs. G: OR = 0.84, 95% CI = 0.73-0.96). Our meta-analysis revealed that PD1.3 polymorphism may increase the susceptibility to SLE, particularly in Caucasians, while PD1.6 may be a protective factor to SLE.

Associations of interleukin-6 gene polymorphisms with cancer risk: Evidence based on 49,408 cancer cases and 61,790 controls

Many molecular epidemiologic studies have shown that interleukin-6 (IL-6) polymorphisms are significantly associated with susceptibility for various cancers. However, the conclusions of these studies are inconsistent. The purpose of the present study was to explore the association between three common IL-6 loci (rs1800795, rs1800796, and rs1800797) and the risk for various cancers. We systematically searched the PubMed, Web of Science, Wanfang and China national knowledge infrastructure (CNKI) databases for relevant publications and obtained 108 eligible studies, involving 49,408 cancer patients and 61,790 cancer-free controls. Odds ratio (OR), 95% confidence interval (CI), and false positive reporting probability (FPRP) were used to evaluate cancer risk. All statistical analyses were performed using the R software meta package. We observed a non-significant association between rs1800795 and overall cancer risk, while rs1800797 was found to have a false positive association with overall risk of cancer. Subgroup analyses of rs1800797 also suggested non-significant association and rs1800795 played a protective role in liver cancer. Rs1800796 was found to be associated with overall cancer risk, particularly in Asian patients and those with prostate cancer. These findings provide evidence that IL-6 polymorphisms may affect cancer risk.

CYP17 polymorphisms are associated with decreased risk of breast cancer in Chinese Han women: a case–control study

Introduction CYP17 is the second most important enzyme in estradiol synthesis. Epidemiological studies have shown the associations between CYP17 polymorphisms and cancer risk. We conducted a case–control study to evaluate the relationship between CYP17 polymorphisms (rs743572 and rs2486758) and breast cancer (BC) risk. Patients and methods This case–control study included 560 BC patients and 583 age-matched healthy controls from Northwest China. Two polymorphisms (rs743572 and rs2486758) of CYP17 were genotyped by using Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship. Results Compared with the wild genotype of rs743572, we found a significantly reduced risk of BC associated with the variant genotypes (heterozygote model: OR=0.69, 95% CI=0.53–0.89; homozygote model: OR=0.68, 95% CI=0.49–0.95; dominant model: OR=0.69, 95% CI=0.54–0.87; overdominant model: OR=0.78, 95% CI=0.62–0.98; allele model: OR=0.79, 95% CI=0.66–0.93). For rs2486758 polymorphism, we did not find any difference in any of the genetic models. Further stratification analysis by clinical characteristics showed rs743572 was associated with estrogen receptor status (heterozygote model: OR=2.13, 95% CI=1.47–3.08; homozygote model: OR=3.29, 95% CI=1.94–5.58; dominant model: OR=2.39, 95% CI=1.69–3.37) and progesterone receptor status (homozygote model: OR=3.17, 95% CI=1.82–5.55), but there was no association between rs2486758 and clinical characteristics of BC. Haplotype analysis showed that Grs743572Crs2486758 haplotype was a protective factor of BC (OR=0.52, 95% CI=0.40–0.67). Survival analysis did not find that CYP17 rs743572 polymorphism was associated with triple-negative BC, either in terms of overall survival or progression-free survival. Conclusion Our results suggest that CYP17 polymorphisms may reduce the susceptibility to BC in Chinese women.

Four common polymorphisms of BRIP1 (rs2048718, rs4988344, rs4986764, and rs6504074) and cancer risk: evidence from 13,716 cancer patients and 15,590 cancer-free controls

Previous studies have showed the associations between various BRCA1-interacting protein 1 (BRIP1) polymorphisms and cancer risk. But, these results were inconsistent. This meta-analysis based on 18 studies involving 13,716 cancer patients and 15,590 cancer-free controls is aimed at to evaluate the relationship between the four common SNPs of BRIP1 (rs2048718, rs4988344, rs4986764, and rs6504074) and cancer risk. The results showed a decreased risk of rs2048718 or rs4986764 for cervical cancer rather than breast cancer in the overall population (P < 0.05). However, rs6504074 was associated with gynecologic cancer risk among overall population (P < 0.05). Further stratification analyses by ethnicity indicated that all 4 polymorphisms (rs2048718, rs4988344, rs4986764, and rs6504074) were strongly related to cancer susceptibility in Chinese people (P < 0.05). This meta-analysis showed that rs6504074 may play a decreased risk of gynecologic cancer in the overall population. Rs4988344, rs4986764, and rs6504074 were significantly related to decreasing cancer risk in Chinese population.

FABP1 Polymorphisms Contribute to Hepatocellular Carcinoma Susceptibility in Chinese Population with Liver Cirrhosis: A Case-Control Study

Purpose: Single nucleotide variations in the liver fatty acid binding protein (L-FABP, FABP1) gene lead to changes in cellular signaling pathways and lipid metabolism. FABP1 polymorphisms were associated with some liver diseases, like steatotic hepatocellular carcinoma. However, the association between FABP1 rs1545224 and rs2241883 polymorphisms and hepatitis B virus-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC) has not been reported. We performed this study to explore their relationship. Methods: One thousand individuals (250 healthy controls, 250 chronic HBV (CHB), 250 LC, and 250 HCC patients) were recruited. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were applied to assess the difference in allele and genotype frequencies. Cochran-Armitage trend test was used to evaluate the cumulative effect. Significant difference would be defined when the P value was less than 0.05. Results: The distribution of rs1545224 GG, AG and AA genotypes in healthy controls or CHB carriers was not significant when compared to LC or HCC patients (P>0.05). LC patients carrying at least one A allele are more likely to develop HCC in contrast with those with G allele (P<0.05). After adjustment for confounders, meaningful results were only seen in the comparison between rs1545224 AG+AA genotype carriers and GG genotype carriers among the LC patients (P<0.05). Rs2241883 polymorphism did not influence the risk of developing LC or HCC in healthy and CHB individuals, nor did it influence the risk of HCC in LC patients (P>0.05). Conclusions: Taken together, FABP1 rs1545224 polymorphism might increase HCC risk in LC patients, indicating that FABP1 rs1545224 polymorphism may be related to the process of developing HCC in Chinese patients with LC.

Prognostic Values of LAPTM4B-35 in Human Cancer: A Meta-analysis

Background: Lysosome-associated protein transmembrane-4β-35(LAPTM4B-35) has been observed overexpressed in multiple malignant tumors. However, the prognostic value of LAPTM4B-35 remains controversial. Therefore, we conducted a meta-analysis to evaluate the prognostic value of LAPTM4B-35 in human cancers. Methods: The relevant publications were obtained by systematically searching the PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for the prognosis value of LAPTM4B-35 for cancer patient. Results: Our result suggest that LAPTM4B-35 overexpression is significantly associated with poor overall survival (OS) (HR = 2.49, 95% CI = 1.87-3.32, p < 0.001), disease-free survival (DFS) (HR = 2.43, 95% CI = 1.35-4.35, p = 0.003), and progression-free survival (PFS) (HR = 4.12, 95% CI = 2.30-7.37, p < 0.001). Moreover, subgroup analysis revealed significant association with poor OS in lung (HR = 2.05, 95% CI = 1.37-3.06, p < 0.001), gastric carcinoma (HR = 1.88, 95% CI = 1.01-3.50, p < 0.047) and ovarian cancer (HR = 4.94, 95% CI = 1.44-16.94, p = 0.011). Conclusion: LAPTM4B-35 may be a novel predictive biomarker and a potential target for treatment.

Prognostic value of flotillins (flotillin-1 and flotillin-2) in human cancers: A meta-analysis

Increasing evidence indicates that flotillins which associate with cell infiltration and metastasis are overexpressed in multiple tumors. The prognostic role of flotillins remains controversial. We conducted a comprehensive meta-analysis of published research to investigate the prognostic value of flotillins in patients with cancer. Pooled HRs (hazard ratio) with 95% CIs (confidence interval) were collected to estimate the prognostic value. Twenty-seven studies with 4803 cancer patients were finally identified. The results indicated that: (1) elevated flotillins predicted poorer OS (overall survival) (HRu202f=u202f2.17, 95% CI 1.87 to 2.52; HRu202f=u202f1.61, 95% CI 1.44 to 1.81) and DFS (disease-free survival) (HRu202f=u202f2.41, 95% CI 1.83 to 3.18; HRu202f=u202f3.01, 95% CI 2.12 to 4.27) in patients with cancer; (2) Subgroup analysis showed that the prognostic value of flotillin-1 on OS and DFS in the investigated tumors were not altered by tumor type (such as digestive system cancers, renal cell cancer, lung cancer, or others), country (China or Canada), cutoff value, detection method, analysis type or paper quality and flotillin-2 overexpression indicates poor OS in human cancers except for nasopharyngeal carcinoma. Flotillins are promising as new biomarkers to predict poor prognosis of patients with tumors. This conclusion needs more clinical studies with different types of cancer to be proven.

Prognostic values of HE4 expression in patients with cancer: a meta-analysis

Background To evaluate the prognostic impact of HE4 expression in patients with cancer. Materials and methods We searched the PubMed, Web of Science, Chinese National Knowledge Infrastructure and WangFang databases for publications concerning HE4 expression in patients with cancer. The correlation of HE4 expression level with overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) was analyzed. Results In this meta-analysis, 29 studies, with a total of 4,235 patients, were included. Our results showed that HE4 expression was significantly associated with poorer OS (hazard ratio [HR] =2.15, 95% confidence interval [CI] =1.77–2.62, P<0.001). Further subgroup analysis found that this correlation was not affected by race (White: HR =1.92, 95% CI =1.53–2.39, P<0.001; Asian: HR =2.62, 95% CI =2.06–3.35, P<0.001) or tumor types (endometrial cancer: HR =2.91, 95% CI =1.86–4.53, P<0.001; ovarian cancer: HR =1.82, 95% CI =1.50–2.22, P<0.001; lung cancer: HR =2.31, 95% CI =1.54–3.47, P<0.001). Our meta-analysis showed that HE4 overexpression was significantly associated with DFS (HR =2.50, 95% CI =1.86–3.37, P<0.001) and PFS (HR =1.27, 95% CI =1.11–1.45, P=0.001). Conclusion These results suggest that expression of HE4 was associated with a worse prognosis in patients with cancer. HE4 is a potential novel prognostic factor in patients with cancer.

Association of two FOXP3 polymorphisms with breast cancer susceptibility in Chinese Han women

Background Forkhead box P3 (FOXP3) is a key gene in the immune system which also plays a role in tumor development. This study aims to explore the association of two FOXP3 polymorphisms (rs3761548 and rs3761549) with susceptibility to breast cancer (BC). Method A case–control study was conducted, involving 560 patients and 583 healthy individuals from the Chinese Han population. The genotypes of FOXP3 polymorphisms were detected using the Sequenom MassARRAY method. The association between FOXP3 polymorphisms and BC risk was evaluated using a χ2 test with an odds ratio (OR) and 95% confidence intervals (95% CIs) under six genetic models. False-positive report probability was utilized to examine whether the significant findings were noteworthy. Results We observed that rs3761548 was associated with a higher BC risk in heterozygous, dominant, overdominant, and allele genetic models (CA vs CC: OR =1.32, P=0.031; CA/AA vs CC: OR =1.32, P=0.023; CA vs CC/AA: OR =1.29, P=0.042; A vs C: OR =1.26, P=0.029), whereas no significant association was found between rs3761549 and BC risk. In addition, CA, CA/AA genotype, and A allele of rs3761548 were related to larger tumor size, and the A allele was also correlated with a positive status of Her-2 in BC patients. Conclusion Our study suggests that FOXP3 polymorphism rs3761548 is associated with BC susceptibility in the Chinese and may be involved in tumor progression. Future studies are needed to confirm the results in a larger population with more races.

Identification of long non-coding RNA signatures in triple-negative breast cancer

BackgroundTriple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and lack of targets for therapy. This study aimed to explore the expression profile and potential function of lncRNAs in TNBC through bioinformatic methods.MethodsTwo microarrays of TNBC were obtained from the Gene Expression Omnibus database. Differentially expressed lncRNAs and mRNAs were screened out and the expressions of top lncRNAs and overlapping lncRNAs were validated using data from The Cancer Genome Atlas database. The co-expression analysis of lncRNAs and mRNAs was conducted using R software and functional enrichment analysis for was performed by Metascape. Kaplan–Meier Plotter was used for survival analysis.ResultsA total of 1034 dysregulated lncRNAs were found in the two microarrays, and there were 8 overlapped lncRNAs. Among them, 537 lncRNAs were significantly correlated with 451 protein-coding genes (PCGs). The co-expressed PCGs were mainly enriched in terms including cell division, cell cycle, and protein/DNA binding, and were involved in pathways in cancer and other pathways such as PI3K-Akt, MAPK, ErbB and p53 signaling pathways. Hub-genes in the co-expression network were identified, and 7 of them were associated with relapse-free survival of TNBC (MAGI2-AS3: HRu2009=u20090.51; GGTA1P: HRu2009=u20090.54; NAP1L2: HRu2009=u20090.59; CRABP2: HRu2009=u20090.41; SYNPO2: HRu2009=u20090.50; MKI67: HRu2009=u20092.23; COL4A6: HRu2009=u20091.91; all Pu2009<u20090.05).ConclusionsNumerous lncRNAs were dysregulated in TNBC, and many of them are possibly involved in cancer biology. Several of these lncRNAs were associated with of TNBC prognosis, which can be promising biomarkers.