Analysis of cancer-associated fibroblasts in cervical cancer by single-cell RNA sequencing.

OBJECTIVE: Since scRNA-seq is an effective tool to study tumor heterogeneity, this paper intends to reveal the differences of cervical cancer in patients at the individual cell level by scRNA-seq, and focus on the biological functions of cancer-associated fibroblasts (CAFs) in cervical cancer, facilitating the provision of a new interpretation of the heterogeneity of the microenvironment of cervical cancer, and an in-depth exploration of the pathogenesis of cervical cancer as well as pursuit of effective means of treatment intake. METHODS: 3 cervical cancer specimens were collected by clinical surgery for single-cell RNA sequencing. Cell suspensions of fresh cervical cancer tissues were prepared, and cDNA libraries were created and sequenced on the machine. Furthermore, the sequencing data were analyzed using bioinformatics, including descending clustering of cells, identification of cell populations, mimetic time series analysis, inferCNV, cell communication analysis, and identification of transcription factors. RESULTS: A total of 9 cell types were identified, encompassing T cells, epithelial cells, smooth muscle cells, CAFs, endothelial cells, macrophages, B cells, lymphocytes, and plasma cells. CAFs were further divided into three cell subtypes, named type1 cells, type2 cells, and type3 cells. With key transcription factors for the three cells, TCF21, ZC3H11A, and MYEF2 obtained, this research revealed the communication relationship between CAFs and several other cells, and found an important role of CAFs in the MK signaling pathway. CONCLUSIONS: scRNA-seq technology contributed to exploring the tumor heterogeneity of cervical cancer more deeply, and also further gaining insight into the biological functions of CAFs in cervical cancer.

Predictive value of platelet-to-lymphocyte ratio combined with CA199 levels in postoperative survival of patients with gastric cancer: A retrospective study.

OBJECTIVE: To develop a new scoring system based on platelet-to-lymphocyte ratio (PLR) and CA199 to predict the prognosis of gastric cancer. METHODS: PLR-CA199 was identified in a retrospective study that was conducted in a training cohort of 990 gastric cancer patients who underwent curable resection from 2012 to 2014 and validated in a validation cohort of 625 patients between 2015 and 2016. RESULTS: In the training cohort, PLR-CA199 was related to gender (P = 0.041), age (P = 0.014), tumor location (P = 0.015), tumor size (P < 0.001), Bormann type (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and TNM staging (P < 0.001). In the validation cohort, PLR-CA199 was related to tumor size (P < 0.001), Bormann type (P = 0.007), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and TNM staging (P < 0.001). Survival analysis showed that in the training cohort the mean disease-free survival (DFS) was 70.699 months for patients PLR-CA199 = 0, 51.223 months for patients PLR-CA199 = 1, and 32.152 months for patients PLR-CA199 = 2 (P < 0.001). The correlation between PLR-CA199 and DFS was further confirmed in the validation cohort (50.640 vs. 41.842 vs. 22.382, P < 0.001). Survival analysis showed that the mean disease special survival (DSS) was 76.668 months for patients PLR-CA199 = 0, 61.218 months for patients PLR-CA199 = 1, and 44.665 months for patients PLR-CA199 = 2 in the training cohort (P < 0.001). The correlation between PLR-CA199 and DSS was further confirmed in the validation cohort (53.858 vs. 46.385 vs. 44.665, P < 0.001). Furthermore, univariate and multivariate analyses showed that PLR-CA199 was an independent prognostic factor for DFS and DSS. CONCLUSIONS: Preoperative PLR-CA199 may be a useful prognostic indicator, and is a promising tool for predicting the prognosis for gastric cancer.

The Role of Ferroptosis-Related Molecules and Significance of Ferroptosis Score in Cervical Cancer.

Background: Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, may be a potential treatment for many cancers, including cervical cancer (CC). However, the regulation of long noncoding RNAs (lncRNAs) in the process of ferroptosis and whether ferroptosis inducers could increase the cytotoxicity of conventional chemotherapy drugs remain to be further elucidated. Methods: We analyzed the variation of 55 differentially ferroptosis-related genes (FRGs) and the influence of mutations in CC patients. The patients with CC were classified into two ferroptosis clusters by the non-negative matrix factorization (NMF) algorithm. The principal components analysis (PCA) was used to measure the ferroptosis score (FerroScore) in patients with CC. Besides, FerroScore was used to predict the sensitivity of chemotherapy and responses to immunotherapy in patients with CC. Finally, experiments were performed to verify the regulatory effect of AC026790.1 on erastin-induced ferroptosis, as well as the effect of erastin in combination with cisplatin on the toxicity of CC cells (SiHa, HeLa). Result: There were significant differences in the overall survival and immune cell infiltration between the two ferroptosis clusters. Patients with low FerroScore were more sensitive to chemotherapy drugs such as cisplatin and docetaxel. The low-FerroScore group had higher CD8+ T cell infiltration and immune checkpoint expression, demonstrating that patients with lower FerroScores were more sensitive to immunotherapy, which was consistent with the result of the submap method. In vitro, overexpression of AC026790.1 could promote erastin-induced ferroptosis, and the combination of erastin and cisplatin could increase the toxicity of CC cells. Conclusion: FerroScore has a potential prognostic value for CC that may provide a reference for chemotherapy and immunotherapy. LncRNA AC026790.1 can influence ferroptosis, and the combination of ferroptosis inducers and chemotherapy drugs can provide a new perspective on cancer treatment.

Constructing a Novel Signature Based on Immune-Related lncRNA to Improve Prognosis Prediction of Cervical Squamous Cell Carcinoma Patients.

We downloaded gene expression data, clinical data, and somatic mutation data of cervical squamous cell carcinoma (CSCC) patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Predictive lncRNAs were screened using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression, and risk scores were calculated for each patient according to the expression levels of lncRNAs and regression coefficients to establish a risk model that could be a novel signature. We assessed the correlation between immune infiltration status, chemotherapeutics sensitivity, immune checkpoint proteins (ICP), and the signature. Therefore, we selected 11 immune-related lncRNAs (WWC2,AS2, STXBP5.AS1, ERICH6.AS1, USP30.AS1, LINC02073, RBAKDN, IL21R.AS1, LINC02078, DLEU1, LINC00426, BOLA3.AS1) to construct the risk model. Patients who were in the high-risk group had a shorter survival time than those in the low-risk group (p < 0.001). Risk scores in the signature were negatively correlated with macrophage M1, macrophage M2, and T cell CD8 + ; what's more, T cell CD8 + was higher in the low-risk group. The expression levels of ICP such as PD-L1, PD-1, CTLA-4, TIGIT, LAG-3, and TIM-3 were substantially higher in the low-risk group. For chemotherapeutic agents, high-risk scores were associated with higher half-inhibitory concentrations (IC50) of cisplatin. These findings suggested that the risk model can be a novel signature for predicting CSCC patients' prognosis, and it also can be used to formulate clinical treatment plans for CSCC patients.

Integrated analysis of key microRNAs /TFs /mRNAs/ in HPV-positive cervical cancer based on microRNA sequencing and bioinformatics analysis.

BACKGROUND: Cervical squamous cell carcinoma (CESC) is one of the most common malignancies associated with mortality in females. Its onset and prognosis are primarily concerned with persistent infection with high-risk types of human papillomavirus (HPV). However, the molecular mechanisms of HPV-positive CESC remain unclear. METHODS: In this study, we conducted a high-throughput sequencing to identify differentially expressed miRNAs (DEMs). Besides, three series were selected from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Then the miRNA-TF-gene regulatory network was constructed using bioinformatic methods. Genes in the network were performed functional enrichment analysis and protein-protein interaction (PPI) network analysis. Ultimately, the expression levels of six key miRNAs, TFs, and mRNAs were validated by 20 HPV-positive CESC tissues and 15 normal cervical samples. RESULTS: A total of 52 DEMs and 300 DEGs differed between the HPV-positive CESC and normal cervical samples. Then the miRNA-TF-gene regulatory network was constructed consisting of 22 miRNAs, 6 TFs, and 76 corresponding genes, among which miR-149-5p, miRNA-1248 and E2F4 acted as key regulators. PPI network analysis showed that ten genes including TOP2A, AURKA, CHEK1, KIF11, MCM4, MKI67, DTL, FOXM1, SMC4, and FBXO5 were recognized as hub genes with the highest connectivity degrees. Besides, five key molecules miRNA-149-5p, E2F4, KIF11, DTL, and SMC4 were suggested to play crucial roles in the development of HPV-positive CESC. CONCLUSION: These results present a unique insight into the pathological mechanisms of HPV-positive CESC and possibly provides potential therapeutic targets.

LRP1B Polymorphisms Are Associated with Multiple Myeloma Risk in a Chinese Han Population.

Multiple myeloma (MM) is an extremely complex plasma cell malignancy that is genetically heterogeneous. A recent Genome-wide association study (GWAS) indicated that variation at 2q22 (rs61070260) influences MM risk. This association has not been validated to date in a Chinese Han population. In this study, we evaluated the association between rs61070260 in LRP1B and MM risk in a Chinese Han population involving 739 MM patients and 592 healthy controls. Our results indicated that rs61070260 in LRP1B was significantly associated with MM susceptibility (P=3.937×10-37). Furthermore, the linkage disequilibrium (LD) analysis of rs61070260 revealed an LD block encompassing exons 26, 27 and 28 of the LRP1B gene, and a subsequent sequencing analysis identified three SNPs (rs762074421, rs756168629, rs113600691) in exons 26 and 28 of LRP1B. For the SNP rs756168629 in exon 26, a missense mutation which results in a transition from arginine to histidine at position 1661 of the LRP1B protein, has not been found in Chinese populations according to the Chinese Millionome Database and Genome Aggregation Database (EAS), and this mutation was predicted to be deleterious or damaging by SIFT and PolyPhen. These findings firmly establish the role of LRP1B in contributing to MM susceptibility. In addition, the identification of a rare coding mutation (p.R1661H) in LRP1B detected in MM individuals was suggested to be harmful to the encoded protein, which was characterized as a candidate tumour suppressor; thus, LRP1B is likely to be a disease-associated gene that is implicated in the development and progression of MM.

Integrated analysis of dysregulated long non-coding RNAs/microRNAs/mRNAs in metastasis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), largely remains a primary cause of cancer-related death worldwide. The molecular mechanisms in LUAD metastasis have not been completely uncovered. METHODS: In this study, we identified differentially expressed genes (DEGs), miRNAs (DEMs) and lncRNAs (DELs) underlying metastasis of LUAD from The Cancer Genome Atlas database. Intersection mRNAs were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and co-expression network analysis. In addition, survival analyses of intersection mRNAs were conducted. Finally, intersection mRNAs, miRNAs and lncRNAs were subjected to construct miRNA-mRNA-lncRNA network. RESULTS: A total of 1015 DEGs, 54 DEMs and 22 DELs were identified in LUAD metastasis and non-metastasis samples. GO and KEGG pathway analysis had proven that the functions of intersection mRNAs were closely related with many important processes in cancer pathogenesis. Among the co-expression interactions network, 22 genes in the co-expression network were over the degree 20. These genes imply that they have connections with many other gene nodes. In addition, 14 target genes (ARHGAP11A, ASPM, HELLS, PRC1, TMPO, ARHGAP30, CD52, IL16, IRF8, P2RY13, PRKCB, PTPRC, SASH3 and TRAF3IP3) were found to be associated with survival in patients with LUAD significantly (log-rank P < 0.05). Two lncRNAs (LOC96610 and ADAM6) acting as ceRNAs were identified based on the miRNA-mRNA-lncRNA network. CONCLUSIONS: Taken together, the results may provide a novel perspective to develop a multiple gene diagnostic tool for LUAD prognosis, which might also provide potential biomarkers or therapeutic targets for LUAD.

The possible association between the presence of an MPO -463 G > A (rs2333227) polymorphism and cervical cancer risk.

PURPOSE: The association between myeloperoxidase (MPO) polymorphism and the risk of cervical cancer is inconclusive. We performed a meta-analysis to clarify if a correlation exists between MPO polymorphism and the risk for developing cervical cancer. METHODS: All case-control research studies that determined a relationship between MPO and cervical cancer reported up until March 1, 2018 in PubMed, Web of Science, VIP, WanFang, and the CNKI Database were accessed and included. The strength of association was evaluated with pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). We used sensitivity analysis to detect the stability of our results, conducted Q-test to evaluate heterogeneity and applied Begg's funnel plot and Egger's test to investigate any publication bias among selected studies. RESULTS: In this meta-analysis, we included 5 eligible studies in the final evaluation, which included 1125 patients with cervical cancer and 1150 cancer-free control patients. A potential association between the MPO -463 G > A polymorphism and cervical cancer risk was observed (recessive model: OR = 0.65, 95%, CI: 0.43-0.98, P = 0.038; homozygous model: OR = 0.65, 95%, CI: 0.43-0.99, P = 0.045), which indicates that genotype AA reduces the risk of cervical cancer by 35% compared to GG/GA or GG genotypes in our results. A stratified analysis by ethnicity identified a significant correlation among Caucasian patients (recessive model: OR = 0.57, 95%, CI: 0.34-0.95, P = 0.029; homozygous model: OR = 0.60, 95%, CI: 0.36-0.99, P = 0.048) and a stratified analysis by source of control identified a significant correlation among population-based studies. CONCLUSIONS: Our results suggest that the presence of polymorphism, -463 G > A in patients might offer them protection against cervical cancer. By implementing randomized case-control or cohort studies with larger sample sizes, the clinical significance of our results can be further strengthened and verified.

ERCC1 rs11615 polymorphism increases susceptibility to breast cancer: a meta-analysis of 4547 individuals.

Excision repair cross-complementation group 1 (ERCC1), a DNA repair protein, is vital for maintaining genomic fidelity and integrity. Despite the fact that a mounting body of case-control studies has concentrated on investigating the association of the ERCC1 rs11615 polymorphism and breast cancer risk, there is still no consensus on it. We conducted the current meta-analysis of all eligible articles to reach a much more explicit conclusion on this ambiguous association. A total of seven studies involving 2354 breast cancer cases and 2193 controls were elaborately selected for this analysis from the Embase, EBSCO, PubMed, WanFang, and China National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated in our meta-analysis. We found that the ERCC1 rs11615 polymorphism was significantly associated with breast cancer risk under all genetic models. When excluded, the studies that deviated from Hardy-Weinberg equilibrium (HWE), the pooled results of what remained significantly increase the risk of breast cancer under the allele model (OR = 1.14, 95% CI = 1.02-1.27, P=0.02), heterozygote model (OR = 1.24, 95% CI = 1.06-1.44, P=0.007), and dominant model (OR = 1.21, 95% CI = 1.05-1.41, P=0.01). This increased breast cancer risk was found in Asian population as well as under the heterozygote model (OR = 1.24, 95% CI = 1.05-1.48, P=0.013) and dominant model (OR = 1.20, 95% CI = 1.02-1.42, P=0.03). Our results suggest that the ERCC1 rs11615 polymorphism is associated with breast cancer susceptibility, and in particular, this increased risk of breast cancer existence in Asian population.

NOTCH4 is a possible novel susceptibility gene for dilated cardiomyopathy in the Chinese population: A case-control study.

BACKGROUND: The incidence of dilated cardiomyopathy (DCM) has increased in recent years, and many studies have sought to further improve the general understanding of this condition. Previous studies have demonstrated that some single nucleotide polymorphisms (SNPs) associated with systemic lupus erythematosus also affect susceptibility to DCM, suggesting that immune-related diseases may share similar genetic susceptibility. Recent large-scale and genome-wide association studies have identified NCR3, NOTCH4, CYP1A2, ITGA1, OPRM1, ST8SIA2, and LINC00704 as genetic risk factors associated with cardiac manifestations of neonatal lupus. Here, we aimed to determine whether these SNPs conferred susceptibility to DCM in the Chinese Han population. METHODS: We investigated the relationship between these polymorphisms and DCM risk in 273 patients with DCM and 548 healthy controls. Genotyping was performed using MassArray iPLEX system. RESULTS: Logistic regression analysis indicated that the T allele of rs3134942 in NOTCH4 gene increased the risk of DCM by 61% compared with the G allele (Pa  = 6.57 × 10-3 ). The SNP rs3134942 was also significantly associated with increased DCM risk in the additive (Pa  = 6.57 × 10-3 ) and dominant models (Pa  = 1.01 × 10-2 ). Additionally, rs2472299 in CYP1A2 gene showed suggestive association with reduced risk of DCM in the dominant model (Pa  = 4.24 × 10-2 ) and was correlated with smoking status in patients with DCM (Pa  = 1.56 × 10-2 ). CONCLUSIONS: Our findings suggested that rs3134942 in NOTCH4 may be involved in DCM risk. Further, studies in larger and ethnically diverse populations are required to confirm the results reported in this study.

Association between NME1 polymorphisms and cancer susceptibility: A meta-analysis based on 1644 cases and 2038 controls.

The association between polymorphisms in the nucleoside diphosphate kinase 1 (NME1) gene and overall risk of cancer remains to be elucidated. Here, we performed a meta-analysis of the association between rs16949649, rs2302254, and rs34214448 polymorphisms in the NME1 gene and cancer risk. PubMed, Web of Science, and CNKI databases (as of June 6, 2017) were searched. Eight studies, encompassing 1644 cases and 2038 controls, were selected. The results revealed no significant relationship between NME1 polymorphisms and overall cancer susceptibility. Interestingly, the rs16949649 polymorphism was associated with increased susceptibility to gynecological cancer (heterozygous model: odds ratio [OR] = 1.74, 95% confidence interval [CI] = 1.06-2.86, P = 0.029). The rs2302254 polymorphism was linked to decreased susceptibility to gastric cancer in the other groups (recessive model: OR = 0.53, 95% CI = 0.28-0.98, P = 0.045). The rs34214448 polymorphism correlated significantly with increased susceptibility to non-small cell lung cancer according to all genetic models (P < 0.05) and was linked to decreased risk in cervical cancer (recessive model: OR = 0.51, 95% CI = 0.27-0.94, P = 0.031). Thus, our meta-analysis found rs16949649 associated with increased susceptibility to gynecological cancer and rs2302254 was linked to reduced gastric cancer risk; additional, larger studies are required to confirm these findings.

MicroRNA-30a Mediates Cell Migration and Invasion by Targeting Metadherin in Colorectal Cancer.

MicroRNAs play critical roles in the occurrence and progression in various cancers including colorectal cancer. Here, we found that microRNA-30a expression was significantly downregulated in colorectal cancer tissues compared to adjacent noncancerous tissues, and the suppression levels of microRNA-30a were significantly associated with tumor differentiation and lymph node metastasis. We also discovered that the expression level of microRNA-30a was inversely proportional to the invasive potential of several colorectal cancer cell lines. Moreover, overexpression of microRNA-30a in colorectal cancer cells inhibited activity of cell migration and invasion. Luciferase reporter assay confirmed metadherin could be a direct target of microRNA-30a, as the overexpression of microRNA-30a decreased metadherin expression at both the protein and messenger RNA levels. Furthermore, the knockdown of metadherin expression in SW620 significantly decreased cell metastasis and invasion. The upregulation of metadherin at the protein level negatively correlated with the expression of microRNA-30a in colorectal cancer tissues, and this upregulation could partially attenuate the effect induced by microRNA-30a. These findings indicate that microRNA-30a may act as a tumor suppressor in colorectal cancer and that microRNA-30a represses cell migration and invasion by decreasing metadherin, highlighting the therapeutic potential of microRNA-30a and metadherin in colorectal cancer treatment.

Risk alleles for IgA nephropathy-associated SNPs conferred completely opposite effects to idiopathic membranous nephropathy in Chinese Han.

The coexistence of immunoglobulin A nephropathy (IgAN) and idiopathic membranous nephropathy (IMN) in a few cases suggested that there could be existed a similar mechanism in pathogenesis of these two types of primary glomerulonephritis. In order to verify this hypothesis, a total of 23 reported IgAN-associated SNPs were genotyped in a cohort of 485 IMN patients and 569 healthy controls with Chinese Han origin. After Cochran-Armitage test for trend analysis, seven IgAN-associated SNPs located in the major histocompatibility complex (MHC) region were found to be significantly associated with the susceptibility of IMN, with rs9275596 as the top one (p = 1.97E-43, OR = 3.977). It was worth mentioning that the minor alleles of the SNPs conferred completely opposite effects on the pathogenesis of IMN and IgAN, suggesting quite different roles played by these SNPs for these two kinds of primary glomerulonephritis. Conditional logistic regression analysis displayed that SNPs protective from IMN (odds ratio < 1.00) were still significantly associated with IMN (p = 3.67E-4 for rs660895 and p = 1.26E-4 for rs9275224) with the most significant SNP rs9275596 as a covariate. Haplotype-based analysis showed that the seven SNPs were mapped to independent linkage disequilibrium (LD) blocks. Moreover, three out of these seven SNPs, including rs9275224, rs660895, and rs9357155, were found to be potential expression quantitative trait loci (eQTLs) for HLA-DQ molecules. Out of the purpose of identifying the causal variants for IMN within the MHC region, imputation analysis was performed using genotype data of Chinese Han released by the 1000 Genome Project and identified hundreds of SNPs potentially associated with the disease. In brief, our analysis revealed a significant association with the susceptibility of idiopathic membranous nephropathy for the IgAN-correlated SNPs. These SNPs conferred a completely different role for the pathogenesis of these two kinds of diseases.

Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is an autoimmune disease and the leading cause of adult nephritic syndrome. HLA-DQA1 had been identified to be associated with IMN in Europeans and the result was replicated in Chinese Han population. In this study, six single nucleotide polymorphisms (SNPs) in the promoter of HLA-DQA1 and other two SNPs with IgA nephropathy were included for the association analysis. METHODS: The SNPs were genotyped in 509 patients and 601 controls by the MassArray iPLEX. The quantification of anti-phospholipase A2 receptor (PLA2R) antibodies in sera of IMN patients was performed by anti-PLA2R ELISA (IgG) kit. RESULTS: After analysis, four SNPs were significantly associated with IMN, with rs2187668 and rs28383345 as the top two signals (P = 8.42×10-5 and 2.48×10-5, respectively). Even under dominant model, the two SNPs were still significantly associated with IMN (P = 3.50×10-3 for rs28383345 and P = 6.55×10-5 for rs2187668). After conditional study with rs2187668, rs28383345 was the only variant significantly correlated with IMN after Bonferroni correction (P = 0.016). The minor alleles of the two SNPs were also mutually exclusive in our cohort. This indicated that the two SNPs were independently associated with IMN in Chinese Han population. Levels of anti-PLA2R autoantibodies were correlated with the genotypes of the two SNPs, but not significantly (P>0.05). CONCLUSIONS: Our results revealed that a novel independent variant in the promoter of HLA-DQA1 was associated with IMN in Chinese Han population. The locus possessed regulatory role according to the data of RegulomeDB. The exact role of the SNPs on the expression of HLA-DQA1 needs further investigation.

NCOA1 is a novel susceptibility gene for multiple myeloma in the Chinese population: A case-control study.

Multiple myeloma (MM) is an incurable malignancy of mature B-lymphoid cells, and its pathogenesis is only partially understood. Previous studies have demonstrated that a number of Non-Hodgkin Lymphoma (NHL) associated genes also show susceptibility to MM, suggesting malignancies originating from B cells may share similar genetic susceptibility. Several recent large-scale genome-wide association studies (GWAS) have identified HLA-I, HLA-II, CXCR5, ETS1, LPP and NCOA1 genes as genetic risk factors associated with NHL, and this study aimed to investigate whether these genes polymorphisms confer susceptibility with MM in the Chinese Han population. In 827 MM cases and 709 healthy controls of Chinese Han, seven single nucleotide polymorphisms (SNPs) in the HLA-I region (rs6457327), the HLA-II region (rs2647012 and rs7755224), the CXCR5 gene (rs4938573), the ETS1 gene (rs4937362), the LPP gene (rs6444305), and the NCOA1 region (rs79480871) were genotyped using the Sequenom platform. Our study indicated that genotype and allele frequencies of rs79480871 showed strong associations with MM patients (pa = 3.5×10-4 and pa = 1.5×10-4), and the rs6457327 genotype was more readily associated with MM patients than with controls (pa = 4.9×10-3). This study was the first to reveal the correlation between NCOA1 gene polymorphisms and MM patients, indicating that NCOA1 might be a novel susceptibility gene for MM patients in the Chinese Han population.

Association of XRCC1 Arg399Gln and Arg194Trp polymorphisms with susceptibility to multiple autoimmune diseases: a meta-analysis.

The role of the X-ray repair cross-complementing gene 1(XRCC1) Arg399Gln and Arg194Trp polymorphisms has been involved in the investigations of susceptibility to multiple autoimmune diseases, but the results were inconsistent. Here, we have performed a meta-analysis to clarify the relationship between them. All appropriate case-control studies were searched in the PubMed, EMBASE and Chinese National Knowledge Infrastructure (CNKI) database. A meta-analysis was conducted on the association between the XRCC1 two polymorphisms (Arg399Gln, Arg194Trp) and risk of autoimmune diseases. Pooled odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association. Fourteen relevant studies with a total of 2886 cases and 3257 controls were analyzed in our research. Analysis for the XRCC1 Arg399Gln polymorphism under recessive model (OR 1.53, 95% CI 1.07-2.18, P = 0.019), dominant model (OR 1.36, 95% CI 1.04-1.77, P = 0.026) and homozygous model (OR 1.67, 95% CI 1.07-2.62, P = 0.024) indicated an association in the overall population, as well as in Caucasian populations under the recessive model (OR 1.73, 95% CI 1.03-2.91, P = 0.039) and Asian populations under dominant model (OR 1.31, 95% CI 1.02-1.70, P = 0.037). Stratification by disease indicated significant association between XRCC1 Arg399Gln and rheumatoid arthritis (RA) in all genetic models (P < 0.05). However, there was no significant association between XRCC1 Arg194Trp polymorphism and autoimmune diseases in different genetic models. The current meta-analysis demonstrates that the XRCC1 Arg399Gln polymorphism confers susceptibility to autoimmune diseases in Asians and Caucasians and, in particular, shows that XRCC1 Arg399Gln polymorphism is associated with RA.

Efficacy and Safety of Belimumab Plus Standard Therapy in Patients With Systemic Lupus Erythematosus: A Meta-analysis.

PURPOSE: The treatment of belimumab plus standard therapy in patients with systemic lupus erythematosus (SLE) has been studied extensively in recent years. Our aim was to estimate the efficacy and safety of this therapy compared with placebo plus standard therapy in patients with SLE. METHODS: PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese), and Wanfang Database (Chinese) were searched for all randomized clinical trials that mainly studied the efficacy and safety of belimumab plus standard therapy before June 2015. We extracted or calculated the rate of the SLE Response Index and adverse event rate at 52 weeks in all the included studies. The odds ratio (OR) with 95% CI between the 2 groups in this meta-analysis was conducted by using a random-effects model. Sensitivity and publication bias analyses were also performed. All statistical tests were performed by using Stata software version 12.0 (StataCorp., College Station, Texas). FINDINGS: In the overall samples (4 studies, N = 4692 ), a significantly higher SLE Response Index rate at 52 weeks was found in belimumab plus standard therapy group compared with the placebo plus standard therapy group in all studies (OR = 1.49; 95% CI, 1.26-1.77 ; P < 0.001 ). When assessed with the incidence of serious adverse events, the data revealed that there was no significant difference between the 2 groups, with pooled OR = 1.08; 95% CI, 0.83-1.39; P = 0.573; OR = 1.23; 95% CI, 1.02-1.48; P = 0.029; and OR = 1.07; 95% CI, 0.88-1.29; P = 0.506. IMPLICATIONS: The results suggest that treatment with belimumab plus standard therapy is more effective than placebo plus standard therapy in SLE patients, which represents major progress in the treatment of SLE. Regardless of the statistical analyses, further research is necessary to optimize treatment effects.

MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF.

MicroRNAs (miRNAs) play critical roles in the development and progression of ovarian cancer. We found that miR-212 was significantly downregulated in serum and tissues from epithelial ovarian cancer (EOC) patients. Overexpression of miR-212 in ovarian cancer cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay confirmed HBEGF as a direct target of miR-212. Overexpression of miR-212 decreased HBEGF expression at both the protein and messenger RNA (mRNA) levels. Knockdown of HBEGF expression in SKOV3 cell line significantly inhibited cell growth, migration, and invasion. HBEGF mRNA level was upregulated in EOC tissues and inversely correlated with miR-212 expression in tissues. Upregulation of HBEGF could attenuate the effect induced by miR-212. These findings indicate that miR-212 displays a tumor-suppressive effect in human ovarian cancer. And miR-212 suppresses cell proliferation, migration, and invasion by targeting the HBEGF transcript, highlighting the therapeutic potential of miR-212 and HBEGF in epithelial ovarian cancer treatment.

Rapid screening for Chlamydia trachomatis infection by detecting α-mannosidase activity in urogenital tract specimens.

BACKGROUND: Chlamydia trachomatis may cause multiple different urogenital tract disorders, but current non-culture assays for rapid screening of C. trachomatis typically use immunochromatography-based methods. We established another new rapid non-culture method for detection of C. trachomatis based on the measurement of α-mannosidase enzymatic activity in urogenital tract specimens. METHOD: To evaluate the performance of this method, α-mannosidase activities of C. trachomatis serotype D strain 、 and 29 standard strains related to clinical urogenital pathogens were investigated. Furthermore, 553 urogenital tract specimens were used for clinical assays via cell culture method and ligase chain reaction method (LCR), adopting an expanded gold standard. RESULTS: Only C. trachomatis was positive for α-mannosidase activity among different types of microbes tested in the research. When prostate fluid specimens, which have some interfering activity, were excluded, the sensitivity and specificity of the enzymatic method were 91.8% (78/85) and 98.3% (409/416), respectively. There were no significant differences (P > 0.05). CONCLUSIONS: These results showed that α-mannosidase activity could be utilised as a screening marker of C. trachomatis infection.