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BACKGROUND: Hepatocellular carcinoma (HCC) has a high degree of malignancy and poor prognosis. N6-methyladenosine (m6A) modifications and microRNAs (miRNAs) play pivotal roles in tumorigenesis and development. However, the role of m6A-related miRNAs in HCC has not been clarified yet. This study aimed to identify the role of m6A-miRNAs in HCC prognosis through bioinformatics analysis. METHODS: The clinicopathological information and RNA sequencing data of 369 HCC tumor tissues and 49 tumor-adjacent tissues were downloaded from the TCGA database. A total of 23 m6A regulators were extracted to evaluated the m6A-related miRNAs using Pearson's correlation analysis. Then, we selected prognosis-related m6A-miRNAs using a univariate Cox regression model and used the consensus cluster analysis to explore the characteristics of the m6A-miRNAs. The coefficient of the least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct a prognostic risk score model. The receiver operated characteristic (ROC) analysis was applied to evaluate the prognostic value of the signature. The biological functions of targeted genes were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Then, to validate the potential predictive value for prognosis, the miRNA expression profiles from the GSE76903 and GSE6857 were used. Single sample Gene Set Enrichment Analysis (ssGSEA) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were applied to assess the immune microenvironment of HCC. Additionally, a meta-analysis was used to verify the prognostic value of the m6A-microRNAs. RT-PCR was applied to validated the expression of miRNAs in HCC tissues. Cell viability, transwell assay and RNA m6A dot blot assays of HCC cells was applied to access the function of miR-17-5p. RESULTS: The expression of 48 m6A-related miRNAs was identified and 17 prognostic m6A-miRNAs was discovered. The expression profile of those 17 miRNAs was divided into three clusters, and these clusters were associated with the tumor microenvironment (TME) and prognosis. The nine m6A-related miRNA signature was associated with the prognosis of HCC, the AUC of the ROC was 0.771(TCGA dataset), 0.788(GSE76903) and 0.646(GSE6857). The TME and the expression of immune checkpoint molecules were associated with the risk score. The meta-analysis also validated the prognostic value of the m6A-related miRNAs (miR182-5p (HR:1.58, 95%CI:1.04-2.40) and miR-17-5p (HR:1.58, 95%CI: 1.04–2.40)). The expression of miR-17-5p was upregulated in HCC tissues and miR-17-5p showed an oncogenic role in HCC cells. CONCLUSION: The clinical innovation is the use of m6A-miRNAs as biomarkers for predicting prognosis regarding immunotherapy response in HCC patients. [ABSTRACT FROM AUTHOR]

A synchronous control system of virtual main-axis based on extended sliding mode disturbance observer is designed to solve some problems that coupling of multi-axis synchronous control of electronic gears is low and has poor anti-interference ability, and a large amount of synchronization error callback overshoot in bag-making machines. First, a velocity compensator is designed in order to establish the coupling relationship between the virtual and traction motor. Second, a nonsingular terminal sliding mode controller and a disturbance observer are used to enhance the anti-disturbance capability of the system. Finally, by using MATLAB/Simulink simulation, the viability and superiority of the method in multi-axis synchronous control are proved. The simulation results demonstrate that the control method decreases the synchronization error and the callback overshoot between the traction motors, and enhances the coupling performance and anti-interference ability of the system, which has a more significant impact on the high-performance synchronization control for the multi-traction motor system of the bag-making machine. [ABSTRACT FROM AUTHOR]

BACKGROUND: Numerous studies reveal the clinical significance of tumor microenvironment (TME) in multiple cancers. The association between TME in oral squamous cell carcinoma (OSCC) and clinical outcomes remains unsolved. OBJECTIVE: This study aims to exhibit the TME of OSCC and identified the prognostic marker. METHODS: Gene expression profile and clinical data OSCC patients were from the TCGA database. The validated stage data was from the Gene Expression Omnibus (GSE65858). Immune/stromal scores of each patient were calculated by ESTIMATE algorithm. Biological functional prediction was conducted. Prognostic genes identified by survival analysis. Nomogram and Receiver operating characteristic curves were employed to test the predicting power. TIMER database was applied to evaluated the immune infiltrates. RESULTS: Lower immune scores were observed in male patients (P = 0.0107) and different primary tumor sites of oral cavity with different stromal scores (P = 0.0328). The Differentially expressed genes (DEGs) were involved in immune related pathways. HGF gene (hepatocyte growth factor) was prognostic related and with a better prognostic performance when combined with clinical features (AUC = TCGA 0.638, AUC = GEO 0.714). HGF was significantly related with B cell, CD4 ï ⁢ ¼ ⁢ ‹ T cell, CD8 + T cell, macrophage, neutrophils, and dendritic cell infiltration. CONCLUSION: : The current study analyzed the TME and presented immune related prognostic biomarkers for OSCC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to identify prognostic autophagy‐related genes and assess the ability of these genes to predict clinical outcomes in oral squamous cell carcinoma (OSCC). Subjects and methods: The details of the human autophagy‐related genes were obtained from the Human Autophagy Database. The Cancer Genome Atlas database was used to obtain the gene expression profiles and clinical data of patients. Prediction of biological functions of differentially expressed genes was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Prognosis‐related genes were identified by Cox regression analysis, and the coefficient was applied to construct a prognostic risk score model. The median of the risk score was applied to distinguish between high‐ and low‐risk groups. The Gene Expression Omnibus database, qRT‐PCR and immunohistochemistry were used to validate the expression of key genes. Results: KEGG analyses revealed that differentially expressed genes were mainly enriched in autophagy‐related pathways and virus infection. BAK1, BID, NKX2‐3 and SPHK1 were identified. The risk score model showed that the high‐risk score had poorer overall survival (Kaplan‐Meier analysis, p = 1.79 × 10–7). SPHK1 was upregulated in OSCC tissues and cells, and NXK2‐3 was downregulated. Conclusions: Autophagy‐related gene expression profiles may be a potential biomarker for OSCC prognosis. [ABSTRACT FROM AUTHOR]

Objective: Long non‐coding RNA (lncRNA) MEG3 was associated with multiple types of cancers such as oral squamous cell carcinoma (OSCC). Single nucleotide polymorphisms (SNPs) might affect cancer risk by modifying the function of lncRNAs. But fewer study researched the relationship between SNPs and MEG3 in cancers. Considering these reasons, we supposed SNPs in MEG3 may influence the risk of OSCC. Material and Methods: The selected SNPs in MEG3 were genotyped in 1,428 subjects (444 patients with OSCC and 984 cancer‐free controls). The relationship between SNPs in MEG3 and OSCC risk was calculated by logistic regression analysis. The function of the SNPs was explored by luciferase activity assay. Results: A statistically significant increased risk was observed between rs11160608 and OSCC (Dominant model: adjusted OR = 1.36, 95% CI = 1.06–1.76, p = 0.017). Moreover, the effect of rs11160608 CC genotype with OSCC risk was much strong in drinkers than non‐drinkers (adjusted OR = 1.79, 95% CI = 1.17–2.73, p = 0.007). Furthermore, the luciferase activity of rs11160608 A allele was lower than rs11160608 C allele by luciferase reporter assay. Conclusion: Our study confirmed that the SNP rs11160608 in MEG3 might play an important role in OSCC by interring the binding of miRNA. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play important roles in regulation of gene expressions and likely have involvement in cancer susceptibility and disease progression. MicroRNA-101 (miR-101) has been well established as a tumor suppressor, and aberrant expression of miR-101 levels has been previously reported in different malignancies including head and neck squamous cell carcinoma (HNSCC). However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in the susceptibility to HNSCC remains unclear. In this study, we genotyped 11 selected SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case-control study including 576 HNSCC cases and 1552 cancer-free controls. For the main effect analysis, none of the 11 selected SNPs was associated with HNSCC risk. However, in the stratification analysis by tumor sites, rs578481 and rs705509 in pri-miR-101-1 were significantly associated with risk of oral squamous cell carcinoma (OSCC) (rs578481: adjusted odds ratio (OR) = 1.19, 95 % confidence interval (CI) 1.01-1.39, P = 0.036; rs705509: adjusted OR = 0.85, 95 % CI 0.73-0.98, P = 0.030). Furthermore, combined analysis of the two SNPs revealed that subjects carrying the risk alleles of rs578481 and rs705509 had increased risk of OSCC in a dose-response manner ( P = 0.022). Compared with subjects carrying '0-2' risk alleles, subjects carrying '3-4' risk alleles presented a 1.38-fold increased risk of OSCC. In conclusion, our findings suggested that the SNPs rs578481 and rs705509 locating in pri-miR-101-1 may play a role in genetic susceptibility to OSCC, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: To provide a precise quantification of the association between alcohol and tobacco consumption trends in head and neck cancer patients over the past 45 years. Methods: We combined findings from all studies published until March 2014 and evaluated the association between different levels in alcohol and tobacco consumption and head and neck cancers through a meta-analytic approach. Results: We included 28 studies involving 13830 patients with head and neck cancer. In patients with alcohol consumption, the pooled odds ratio (OR) and 95% confidence interval (CI) were 1.29(1.06-1.57), 2.67(2.05-3.48) and 6.63(5.02-8.74) for light drinkers, moderate drinkers and heavy drinkers, respectively. In patients with tobacco consumption, the pooled OR and 95% CI were 2.33(1.84-2.95), 4.97(3.67-6.71) and 6.77(4.81-9.53) for light smokers, moderate smokers and heavy smokers, respectively. Conclusion: The increased alcohol and tobacco consumption trends increased the risk of head and neck cancer over the past 45 years. Tobacco consumption was found to be a stronger risk factor for head and neck cancer than alcohol consumption. Thus, the control should be considered to limit the intake of alcohol and tobacco. [ABSTRACT FROM AUTHOR]

BACKGROUND: A recent study synthesized several published genome-wide association studies (GWAS) on three types of cancers and identified variants at 6p21.1 and 7p15.3 as candidate susceptibility loci for multiple types of human cancers. However, the role of these loci in the development of head and neck cancer (HNC) is still unclear. METHODS: To evaluate the relationships between genetic variants in these regions and HNC risk, we genotyped two common SNPs rs2494938 at 6p21.1 and rs2285947 at 7p15.3 in a case-control study with a total of 503 HNC cases and 900 controls in Han Chinese. RESULTS: We found that rs2494938 at 6p21.1 was associated with a significantly increased risk of HNC in our population [AA vs. GG: adjusted odds ratio (OR)=1.84, 95% confidence interval (CI)=1.13-3.00, P=0.014; AAvs.GA/GG: adjusted OR=1.78, 95% CI=1.10-2.87, P=0.018]. However, no significant association was observed between rs2285947 at 7p15.3 and HNC risk. CONCLUSION: Our results suggest that genetic variants at 6p21.1 may play an important role in HNC development in Han Chinese, and rs2494938 may be a candidate marker for HNC susceptibility. [ABSTRACT FROM AUTHOR]

Backgrounds: The activation of Toll-like receptors (TLRs) may be an important event in the immune evasion of tumor cell. Recently, numerous studies have investigated the associations between TLR2 −196 to −174 del and two SNPs of TLR4 (rs4986790 and rs4986791) and the susceptibility to different types of cancer; however, the results remain conflicting. The aim of this study was to assess the association between TLR2 and TLR4 polymorphisms and cancer risk in a meta-analysis with eligible published studies. Methodology/Principle Findings: A dataset composed of 14627 cases and 17438 controls from 34 publications were included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and three SNPs of TLRs (TLR2 −196 to −174 del, TLR4 rs4986790 and rs4986791). The results showed that all of these three polymorphisms were significantly associated with the increased cancer risk (dominant model: OR = 1.64, 95% CI: 1.04–2.60 for TLR2 −196 to −174 del; OR = 1.19, 95% CI: 1.01–1.41 for TLR4 rs4986790; and OR = 1.47, 95% CI: 1.120–1.80 for TLR4 rs4986791; respectively). In stratified analysis, we found the effect of TLR2 −196 to −174 del on cancer risk remained significant in the subgroup of Caucasians and South Asians, but not in East Asians. However, the association between rs4986791 and cancer risk was significant in both South Asians and East Asians, but not in Caucasians. Furthermore, the association between rs4986790 and cancer risk was statistically significant in digestive cancers (dominant model: OR = 1.76, 95% CI: 1.13–2.73) and female-specific cancers (dominant model: OR = 1.50, 95% CI: 1.16–1.94). However, no significant association with risk of digestive system cancers was observed for TLR2 −196 to −174 del and TLR4 rs4986791. Conclusions/Significance: This meta-analysis presented additional evidence for the association between TLR2 and TLR4 polymorphisms and cancer risk. Further well-designed investigations with large sample sizes are required to confirm this conclusion. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phospholipase C epsilon 1 (PLCE1) plays crucial roles in carcinogenesis and progression of several cancers. A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus. METHODS: To evaluate the role of the Phospholipase C epsilon 1 (PLCE1) polymorphism in cancer susceptibility. We performed a meta-analysis of all available studies, including 8,689 cases and 10,794 controls to derive a more precise relationship. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between PLCE1 rs2274223 polymorphism and cancer risk. RESULTS: A total of 14 case-control studies were included in the present meta-analysis. Overall significant associations were observed (AG vs. AA: OR=1.17, 95%CI=1.04-1.31; GG vs. AA: OR=1.32, 95%CI=1.06-1.66; AG/GG vs. AA: OR=1.19, 95%CI=1.05-1.34; G vs. A: OR=1.16, 95%CI=1.04-1.29) in all cancer types. In the subgroup analysis, PLCE1 rs2274223 polymorphism was significantly increased risk of cancer in Chinese population by ethnicity and upper aerodigestive tract cancer by cancer types. CONCLUSIONS: Our meta-analysis suggested the PLCE1 rs2274223 might act as a cancer risk factor among all subjects, especially in the Chinese population and upper aerodigestive tract cancer. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that genetic variants at chromosome 8q24 confer susceptibility to various types of cancer. This case-control study was designed to explore the relationship between genetic variants at 8q24 and ovarian cancer risk in Han Chinese women. Two variants (rs13281615 A > G and rs6983267 T > G) were genotyped in 377 ovarian cancer cases and 1034 cancer-free controls using TaqMan allelic discrimination assay. Logistic regression analysis revealed that the G allele of rs6983267 was significantly associated with increased risk of ovarian cancer (additive model: adjusted OR = 1.21, 95% CI = 1.01-1.43, P = 0.048; recessive model: adjusted OR = 1.51, 95% CI = 1.06-2.15, P = 0.023). However, no significant association was observed between rs13281615 and ovarian cancer. In stratified analysis, the risk effect of rs6983267 variant remained significant in premenopausal women (additive model: adjusted OR = 1.62, 95% CI = 1.18-2.23, P = 0.003). Summarily, this study suggested that 8q24 rs6983267 may contribute to the susceptibility of ovarian cancer in premenopausal Han Chinese women, supporting the pleiotropy of 8q24 in carcinogenesis.

Breast cancer 1 (BRCA1) gene makes great contributions to the repair of DNA. The association between BRCA1 P871L polymorphism and cancer risk has been investigated in a growing number of studies, but the conclusions are not conclusive. To obtain a comprehensive conclusion, we performed a meta-analysis of 24 studies with 13762 cases and 22388 controls. The pooled results indicated that BRCA1 gene P871L variant decreased risk of overall cancer (homozygous model: odds ratio (OR) = 0.89, 95%confidence interval (CI) = 0.79-1.00; recessive model: OR = 0.89, 95% CI = 0.80-0.99). The stratified analysis observed decreased risk associated with BRCA1 P871L in subgroups among Asians and high score studies, but not Caucasians or low score studies. In conclusion, despite several limitations, this meta-analysis suggested that BRCA1 P871L genetic variation may be associated with decreased susceptibility to cancer.

Background: MicroRNA (miRNA) polymorphisms may alter miRNA-related processes, and they likely contribute to cancer susceptibility. Various studies have investigated the associations between genetic variants in several key miRNAs and the risk of human cancers; however, few studies have focused on head and neck squamous cell carcinoma (HNSCC) risk. This study aimed to evaluate the associations between several key miRNA polymorphisms and HNSCC risk in a Chinese population., Methods: In this study, we genotyped five common single-nucleotide polymorphisms (SNPs) in several key miRNAs (miR-149 rs2292832, miR-146a rs2910164, miR-605 rs2043556, miR-608 rs4919510, and miR-196a2 rs11614913) and evaluated the associations between these SNPs and HNSCC risk according to cancer site with a case-control study including 576 cases and 1552 controls, which were matched by age and sex in a Chinese population., Results: The results revealed that miR-605 rs2043556 [dominant model: adjusted odds ratio (OR) 0.71, 95% confidence interval (CI) 0.58-0.88; additive model: adjusted OR 0.74, 95% CI 0.62-0.89] and miR-196a2 rs11614913 (dominant model: adjusted OR 1.36, 95% CI 1.08-1.72; additive model: adjusted OR 1.28, 95% CI 1.10-1.48) were significantly associated with the risk of oral squamous cell carcinoma (OSCC). Furthermore, when these two loci were evaluated together based on the number of putative risk alleles (rs2043556 A and rs11614913 G), a significant locus-dosage effect was noted on the risk of OSCC (P trend < 0.001). However, no significant association was detected between the other three SNPs (miR-149 rs2292832, miR-146a rs2910164, and miR-608 rs4919510) and HNSCC risk., Conclusion: Our study provided the evidence that miR-605 rs2043556 and miR-196a2 rs11614913 may have an impact on genetic susceptibility to OSCC in Chinese population.

MicroRNAs (miRNAs) play important roles in regulation of gene expressions and likely have involvement in cancer susceptibility and disease progression. MicroRNA-101 (miR-101) has been well established as a tumor suppressor, and aberrant expression of miR-101 levels has been previously reported in different malignancies including head and neck squamous cell carcinoma (HNSCC). However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in the susceptibility to HNSCC remains unclear. In this study, we genotyped 11 selected SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case-control study including 576 HNSCC cases and 1552 cancer-free controls. For the main effect analysis, none of the 11 selected SNPs was associated with HNSCC risk. However, in the stratification analysis by tumor sites, rs578481 and rs705509 in pri-miR-101-1 were significantly associated with risk of oral squamous cell carcinoma (OSCC) (rs578481: adjusted odds ratio (OR) = 1.19, 95 % confidence interval (CI) 1.01-1.39, P = 0.036; rs705509: adjusted OR = 0.85, 95 % CI 0.73-0.98, P = 0.030). Furthermore, combined analysis of the two SNPs revealed that subjects carrying the risk alleles of rs578481 and rs705509 had increased risk of OSCC in a dose-response manner (P trend = 0.022). Compared with subjects carrying "0-2" risk alleles, subjects carrying "3-4" risk alleles presented a 1.38-fold increased risk of OSCC. In conclusion, our findings suggested that the SNPs rs578481 and rs705509 locating in pri-miR-101-1 may play a role in genetic susceptibility to OSCC, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis.

Let-7 and Lin28 establish a double-negative feedback loop to affect several biological processes, such as differentiation of stem cell, invasion and metastasis, and tumorigenesis. In this study, we systematically investigated the associations between 6 potentially functional SNPs of let7 and Lin28 genes and the risk of oral cavity cancer with a case-control study including 384 oral cavity cancer cases and 731 controls. We found that the variant allele (T) of rs221636 of Lin28B was significantly associated with a reduced risk of oral cavity cancer [odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.58-0.92, P = 7.55 × 10(-3) in additive model]. Bioinformatics prediction indicated that rs221636 was located at the binding site of hsa-miR-548p in the 3' UTR of Lin28B. Luciferase activity assay also showed a lower expression level for rs221636 T allele compared with A allele. These findings indicated that rs221236 located at Lin28B may contribute to the risk of oral cavity cancer through the interruption of miRNA binding.

Backgrounds: The activation of Toll-like receptors (TLRs) may be an important event in the immune evasion of tumor cell. Recently, numerous studies have investigated the associations between TLR2 -196 to -174 del and two SNPs of TLR4 (rs4986790 and rs4986791) and the susceptibility to different types of cancer; however, the results remain conflicting. The aim of this study was to assess the association between TLR2 and TLR4 polymorphisms and cancer risk in a meta-analysis with eligible published studies., Methodology/principle Findings: A dataset composed of 14627 cases and 17438 controls from 34 publications were included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and three SNPs of TLRs (TLR2 -196 to -174 del, TLR4 rs4986790 and rs4986791). The results showed that all of these three polymorphisms were significantly associated with the increased cancer risk (dominant model: OR = 1.64, 95% CI: 1.04-2.60 for TLR2 -196 to -174 del; OR = 1.19, 95% CI: 1.01-1.41 for TLR4 rs4986790; and OR = 1.47, 95% CI: 1.120-1.80 for TLR4 rs4986791; respectively). In stratified analysis, we found the effect of TLR2 -196 to -174 del on cancer risk remained significant in the subgroup of Caucasians and South Asians, but not in East Asians. However, the association between rs4986791 and cancer risk was significant in both South Asians and East Asians, but not in Caucasians. Furthermore, the association between rs4986790 and cancer risk was statistically significant in digestive cancers (dominant model: OR = 1.76, 95% CI: 1.13-2.73) and female-specific cancers (dominant model: OR = 1.50, 95% CI: 1.16-1.94). However, no significant association with risk of digestive system cancers was observed for TLR2 -196 to -174 del and TLR4 rs4986791., Conclusions/significance: This meta-analysis presented additional evidence for the association between TLR2 and TLR4 polymorphisms and cancer risk. Further well-designed investigations with large sample sizes are required to confirm this conclusion.