Potential Role of Circulating MiR-21 in the Diagnosis and Prognosis of Digestive System Cancer: A Systematic Review and Meta-Analysis

Recent evidences indicate that circulating microRNAs (miRNAs) exhibit aberrant expression in the plasma of patients suffering from cancer compared to normal individuals, suggesting that it may be a useful noninvasion diagnostic method. MiR-21 plays crucial roles in carcinogenesis and can be served as a biomarker for the detection of various cancers. Therefore, the aim of this meta-analysis is to assess the potential role of miR-21 for digestive system cancer.By searching the PubMed, Embase, and Web of Science for publications concerning the diagnostic value of miR-21 for digestive system cancer, total of 23 publications were included in this meta-analysis. Receiver operating characteristic curves (ROC) were used to check the overall test performance. For prognostic meta-analysis, pooled hazard ratios (HRs) of circulating miR-21 for survival were calculated.Totally 23 eligible publications were included in this meta-analysis (15 articles for diagnosis and 8 articles for prognosis). For diagnostic meta-analysis, the summary estimates revealed that the pooled sensitivity and specificity were 0.76(95% CI = 0.70–0.82) and 0.84 (95% CI = 0.78–0.89). Besides, the area under the summary ROC curve (AUC) is 0.87. For prognostic meta-analysis, the pooled HR of higher miR-21 expression in circulation was 1.94 (95% CI = 0.99–3.82, P = 0.055), which indicated higher miR-21 expression could be likely to predict poorer survival in digestive system cancer. The subgroup analysis implied the higher expression of miR-21 was correlated with worse overall survival in the Asian population in digestive system cancer (HR = 2.41, 95% CI = 1.21–4.77, P = 0.012).The current evidence suggests circulating miR-21 may be suitable to be a diagnostic and prognostic biomarker for digestive system cancer in the Asians.     

MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer

The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA–mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P = 0.012), coexistence of adenoma (P = 0.012), microsatellite instability (P = 0.024), and less glucose transporter 1 (P = 0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.     

Diagnostic and Prognostic Value of Serum Interleukin-6 in Colorectal Cancer

The application of serum interleukin-6 (IL-6) in the diagnosis and prognosis of colorectal cancer (CRC) has been evaluated in many studies, whereas the results were contradictive.The aim of this study was to systematically evaluate this issue.An original study was conducted to explore the diagnostic value of serum IL-6 in CRC. Pubmed, Embase, and Cochrane library databases were searched for eligible studies.For diagnostic meta-analysis, aggregate data (AD) and individual participant data (IPD) meta-analyses were both adopted. The sensitivity and specificity were pooled and a summary receiver-operating characteristic (ROC) curve was constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of IL-6 for survival were summarized. Secondary analysis of survival data was performed to synthesize the Kaplan–Meier curves.Total 17 studies (including our study) were included in this meta-analysis. The pooled sensitivity, specificity, and area under curve (AUC) of serum IL-6 were 0.72 (95% CI: 0.46–0.88), 0.74 (95% CI: 0.56–0.86), and 0.79 (95% CI: 0.75–0.82) in CRC diagnosis, respectively. Further, IPD meta-analysis strengthened the diagnostic value of serum IL-6 (the AUC, sensitivity, and specificity were 0.794, 0.606, and 0.839, respectively). For prognostic analysis, the high serum level of IL-6 was inversely associated with overall survival (OS) (pooled HR = 1.76, 95% CI: 1.42–2.19, P < 0.001) and disease-free survival (DFS) (pooled HR = 2.97, 95% CI: 1.76–5.01, P < 0.001). The synthesized Kaplan–Meier curves indicated that CRC patients with higher serum IL-6 level had a worse OS (P = 0.0027) and DFS (P < 0.001), which further support the prognostic value of serum IL-6 in CRC patients.The present study confirmed that serum IL-6 may be a potential biomarker for CRC diagnosis, and the high serum IL-6 level was associated with poor prognosis for both CRC overall survival and disease-free survival.The study has been registered in an international registry of systematic reviews PROSPERO (CRD42013006485).     

Diagnostic utility of CT for abdominal injury in the military setting: A systematic review and meta-analysis

Background:It is critical to accurately identify patients with abdominal injury who truly need to undergo laparotomy during the war in timely fashion. The diagnostic utility of computed tomography (CT) for evaluating abdominal injury in the military setting remains uncertain.Methods:PubMed, EMBASE, and Cochrane Library databases were searched. Meta-analyses were performed by using a random-effect model. We pooled the area under the summary receiver operating characteristic curves with standard errors, the Q indexes with standard errors, the sensitivities with 95% confidence intervals (CIs), the specificities with 95% CIs, the positive likelihood ratios with 95% CIs, the negative likelihood ratios with 95% CIs, and the diagnostic odds ratios with 95% CIs. The heterogeneity among studies were evaluated by the I² and P value.Results:Overall, 5 retrospective studies were included. The area under the summary receiver operating characteristic curve was 0.9761 ± 0.0215 and the Q index was 0.9302 ± 0.0378. The pooled sensitivity was 0.97 (95% CI = 0.92–0.99) without a significant heterogeneity among studies (I² = 0%, P = .4538). The pooled specificity was 0.95 (95% CI = 0.93–0.97) with a significant heterogeneity among studies (I² = 90.6%, P < .0001). The pooled positive likelihood ratio was 10.71 (95% CI: 2.91–39.43) with a significant heterogeneity among studies (I² = 89.2%, P < .0001). The pooled negative likelihood ratio was 0.07 (95% CI = 0.02–0.27) with a significant heterogeneity among studies (I² = 57.5%, P = .0516). The pooled diagnostic odds ratio was 177.48 (95% CI = 18.09–1741.31) with a significant heterogeneity among studies (I² = 75.9%, P = .0023).Conclusion:Diagnostic accuracy of CT for abdominal injury is excellent in the military setting. Further work should explore how to shrink CT equipment for a wider use in wartime.     

Association Between IL-4 Polymorphisms and Risk of Liver Disease: An Updated Meta-Analysis

Interleukin-4 (IL-4) polymorphisms have been reported to influence an individual''s susceptibility to liver disease as it is a central anti-inflammatory Th2 cytokine; however, these results remain controversial.A comprehensive meta-analysis of the relevant literature was thus performed to better estimate the relationship between IL-4 polymorphisms and liver disease.Systematic searches of various databases (PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure) for studies published before July 5, 2015 were performed. Odds ratios (ORs) with 95% confidence intervals (CIs) calculated in fixed or random-effects models were used to estimate the strength of the association. Subgroup analyses, meta-regression, Galbraith plots, and sensitivity analyses were also performed.A total of 16 case–control studies, of which 15 involved the -590C/T polymorphism and 3 involved the -33T/C polymorphism, were included in the study. With respect to the -590C/T polymorphism, a significantly increased risk of liver diseases was found in the overall population (TT + CT vs CC: OR = 1.25, 95% CI = 1.06–1.49, P = 0.009 and CT vs CC: OR = 1.22, 95% CI = 1.00–1.48, P = 0.048) and the Asian population (TT + CT vs CC: OR = 1.28, 95% CI = 1.04–1.57, P = 0.020). Further subgroup analyses also showed significant associations between the -590C > T polymorphism and the risk of hepatitis C infection and hepatocellular carcinoma. However, no association was found between the -33T/C polymorphism and risk of liver diseases in all comparison models.This meta-analysis suggested that the IL-4 -590C > T polymorphism is associated with an increased risk of hepatitis C infection and hepatocellular carcinoma, especially among the Asian population.     

COL5A2 as a potential clinical biomarker for gastric cancer and renal metastasis

Background:Gastric cancer, characterized by insidious onset and multiple metastasis, is almost incurable and has poor prognosis, and also one of the leading causes of treatment failure and death in patients with gastric cancer (GC). However, the prognosis of collagen type V alpha2 chain (COL5A2) in GC and renal metastasis is unknown.Methods:Recruited 148 patients who underwent GC. The diagnosis of GC was confirmed by ultrasound imaging and pathological examination. Immunohistochemistry and RT-qPCR were performed to exam the expression level of COL5A2. The statistical methods included Pearson chi-square test, Spearman-rho correlation test, univariate and multivariate cox regression analysis. Finally, this research constructed receiver operating characteristic (ROC) curves and applied the area under the curve (AUC).Results:Based on Pearson''s chi-square test, Spearman-rho test, and univariate/multivariate cox regression, pathologic grade (P < .001), renal metastasis (P < .001) and staging (P < .001) were significantly related to COL5A2. And COL5A2 expression (hazard ratio [HR]: 18.834, P < .001) is an independent risk factor of GC. The AUC was used as the degree of confidence in judging each factor: COL5A2 (AUC = 0.878, P < .001), COL1A1 (AUC = 0.636, P = .006), COL1A2 (AUC = 0.545, P = .368), and COL3A1 (AUC = 0.617, P = .019). Through the ROC result, COL5A2 had more advantage as a biomarker for GC than other collagens.Conclusions:COL5A2 gene expression level might be a risk factor for GC. COL5A2 has a strong correlation with the prognosis of the disease.     

Genetic Variations in Key MicroRNAs are Associated With the Survival of Nonsmall Cell Lung Cancer

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules involved in carcinogenesis. It has been identified that genetic variations in miRNAs contribute to cancer risk, prognosis, and survival. In the present study, we investigated whether single nucleotide polymorphisms (SNPs) of several key miRNAs (miR-184, miR-218, and miR-124) were associated with the prognosis of nonsmall cell lung cancer (NSCLC) in a clinical cohort study including 1001 cases. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs). We found that 5 SNPs were associated with NSCLC survival (rs919968, rs3775815, rs4867902, and rs6122390 in an additive model: adjusted HR = 1.15, 95% CI = 1.02–1.29; adjusted HR = 0.78, 95% CI = 0.67–0.91, adjusted HR = 1.24, 95% CI = 1.09–1.41; adjusted HR = 1.21, 95% CI = 1.07–1.36, respectively; rs298206 in a dominant model: HR = 1.25, 95% CI = 1.05–1.49). Even after the Bonferroni correction, 3 SNPs remained significant (adjusted P = 0.010, 0.010, and 0.032 for rs3775815, rs4867902, and rs6122390, respectively). Additionally, the combined analysis of these 5 SNPs showed a significant locus-dosage effect between number of unfavorable alleles (rs919968-A, rs3775815-C, rs4867902-G, rs6122390-A, and rs298206-T) and death risk of NSCLC (P for trend < 0.001). A statistically significant multiplicative interaction was found between the genotypes of rs4867902 and surgical operation status (P_int = 0.013). These findings indicated that genetic variations in miRNAs (miR-184, miR-218, and miR-124) might be prognostic markers for NSCLC patients.     

Association of the VEGFR2 single nucleotide polymorphism rs2305948 with glioma risk

Background:Many studies have reported a relationship between the vascular endothelial growth factor receptor 2 single nucleotide polymorphism (SNP) rs2305948 and glioma, but their conclusions have been controversial. A meta-analysis was performed to assess the association between rs2305948 and glioma susceptibility.Methods:Inclusion criteria and a strategy for screening of original literature were created. Eligible articles on the correlation between the SNP rs2305948 and glioma were identified in the PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang databases. After extracting the data, Stata 12. 0 software was used to perform statistical analysis under 5 genetic models and to calculate the combined odds ratio (OR) value and its 95% confidence interval (CI).Results:Four case-control studies including 1595 cases and 1657 controls were entered into the study. The overall analysis showed that no obvious association existed between rs2305948 and glioma risk (allele: OR = 1.20, 95% CI = 0.93–1.54, P = .162; dominant: OR = 1.17, 95% CI = 0.93–1.46, P = .174; recessive: OR = 1.72, 95% CI = 0.94–3.15, P = .076; heterozygous: OR = 1.11, 95% CI = 0.94–1.30, P = .226; homozygous: OR = 1.74, 95% CI = 0.92–3.29, P = .088). The subgroup analysis suggested that the SNP rs2305948 was related to glioma susceptibility under allele, dominant, recessive and homozygote models in the Asian population (allele: OR = 1.34, 95% CI = 1.16–1.55, P < .001; recessive: OR = 2.24, 95% CI = 1.49–3.36, P < .001; homozygous: OR = 2.32, 95% CI = 1.54–3.50, P < .001).Conclusion:The vascular endothelial growth factor receptor 2 rs2305948 gene polymorphism may be related to glioma susceptibility in the Asian population. However, the association is not clear in non-Asian populations, for which there has been less research.     

The Polymorphism of CYP2E1 Rsa I/Pst I Gene and Susceptibility to Respiratory System Cancer: A Systematic Review and Meta-Analysis of 34 Studies

The purpose of this articles is to determine whether the cytochrome P450 2E1 (CYP2E1) Rsa I/Pst I gene polymorphism is correlated with respiratory system cancers.Respiratory system cancers included lung cancer, laryngeal cancer, nasopharyngeal cancer, and cancers of other respiratory organs, which are the most common malignant tumors worldwide; the significant relationship between CYP2E1 Rsa I/Pst I gene polymorphism and some respiratory system cancer have been reported, but results of some other studies are controversial. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association.PubMed, EMBASE, Cochrane Library Databases, China National Knowledge Infrastructure, and Wanfang Database (up to July 20, 2014) were searched for all case–control studies those mainly studied the relationship between CYP2E1 Rsa I/Pst I gene polymorphism and the susceptibility of respiratory system cancer.A total of 332 articles were collected, among which 34 studies that involved 7028 cases and 9822 controls fulfilled the inclusion criteria after being assessed by 2 reviewers. When stratified by cancer site, the C2/C2 polymorphism could increase the risk of nasopharyngeal cancer under the homozygote model (C2C2 vs C1C1: OR = 1.85, 95% CI = 1.20–2.85, P = 0.005) and recessive model (C2C2 vs C1C2/C1C1: OR = 1.89, 95% CI = 1.23–2.89, P = 0.003). Protection effect was found in lung cancer in heterozygote model (C1C2 vs C1C1: OR = 0.82, 95% CI = 0.74–0.91, P < 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.83, 95% CI = 0.76–0.90, P < 0.001), and allele contrast model (C2 vs C1: OR = 0.85, 95% CI = 0.73–1.00, P = 0.045). With regard to ethnicity subgroup analysis, there was significant association in Asian population in heterozygote model (C1C2 vs C1C1: OR = 0.85, 95% CI = 0.78–0.94, P = 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.88, 95% CI = 0.81–0.95, P = 0.001), and recessive model (C2C2 vs C1C2/C1C1: OR = 1.25, 95% CI = 1.01–1.53, P = 0.036).CYP2E1 Rsa I/Pst I gene polymorphism may reduce the risk of respiratory system cancer. Furthermore, significant association was also found in Asian populations.     

Long-Term Single and Joint Effects of Excessive Daytime Napping on the HOMA-IR Index and Glycosylated Hemoglobin: A Prospective Cohort Study

This prospective cohort study was conducted to assess the duration of daytime napping and its effect combined with night sleep deprivation on the risk of developing high HOMA-IR (homeostasis model assessment of insulin resistance) index and disadvantageous changes in glycosylated hemoglobin (HbA1c) levels.A total of 5845 diabetes-free subjects (2736 women and 3109 men), 30 to 65 years of age, were targeted for this cohort study since 2008. Multiple adjusted Cox regression models were performed to evaluate the single and joint effects of daytime napping on the risk of an elevated HbA1c level and high HOMA-IR index.After an average of 4.5 years of follow-up, >30 minutes of daytime napping was significantly associated with an increased risk of an elevated HbA1c level (>6.5%) in men and women (all P trend < 0.05). Hazard ratios (HRs) for an HbA1c level between 5.7% and 6.4% were also significant in the entire cohort and women, but nonsignificant in men. HRs (95% confidence interval, CIs) for the high HOMA-IR index in the entire cohort, men, and women were 1.33 (1.10–1.62), 1.46 (1.08–1.98), and 1.47 (1.12–1.91), respectively. The combination of sleep deprivation with no naps or >30 minutes napping and the combination of no sleep deprivation with >30 minutes daytime napping were all associated with an HbA1c level >6.5% (HR = 2.08, 95% CI = 1.24–3.51; HR = 4.00, 95% CI = 2.03–7.90; and HR = 2.05, 95% CI = 1.29–3.27, respectively). No sleep deprivation combined with >30 minutes daytime napping correlated with a high risk of an HbA1c level between 5.7% and 6.4% and high HOMA-IR index (HR = 2.12, 95% CI = 1.48–3.02; and HR = 1.35, 95% CI = 1.10–1.65, respectively).Daytime napping >30 minutes was associated with a high risk of an elevated HbA1c level and high HOMA-IR index. No sleep deprivation combined with napping >30 minutes carries a risk of abnormal glucose metabolism. Sleep deprivation combined with brief daytime napping <30 minutes was not associated with a risk for an elevated HbA1c level and high HOMA-IR index.     

Meta-Analysis of Prognostic and Clinical Significance of CD44v6 in Esophageal Cancer

CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis.We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects.Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR = 9.19, 95% CI = 6.30–13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR = 6.91, 95% CI = 4.81–9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56–3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P > 0.05). Moreover, no publication bias was found among the studies (all P > 0.05).This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages.     

High Expression of MicroRNA-196a Indicates Poor Prognosis in Resected Pancreatic Neuroendocrine Tumor

There is limited data on miRNA expression in pancreatic neuroendocrine tumors (PanNETs). In this study, we aimed to identify miRNAs that could be potential prognostic biomarkers of PanNETs in patients who underwent curative surgery.For miRNA target screening, 2 primary PanNETs and corresponding liver metastases were screened for miRNA expression by the NanoString nCounter analysis. Candidate miRNAs were selected by ≥2-fold difference of expression between metastatic versus primary tumor. For miRNA target validation, quantitative real-time PCR was performed for candidate miRNAs on 37 PanNETs and matched nonneoplastic pancreata, and the miRNA levels were correlated with the clinicopathological features and patient survival data.Eight miRNAs (miRNA-27b, -122, -142–5p, -196a, -223, -590–5p, -630, and -944) were selected as candidate miRNAs. Only miR-196a level was significantly associated with stage, and mitotic count. When PanNETs were stratified into high (n = 10) and low (n = 27) miRNA-196a expression groups, miRNA-196a-high PanNETs were significantly associated with advanced pathologic T stage (50.0% vs 7.4%), N stage (50.0% vs 3.7%), higher mitotic counts (60.0% vs 3.7%), and higher Ki-67-labeling indices (60.0% vs 22.2%). In addition, high miRNA-196a expression was significantly associated with decreased overall survival (P = 0.046) and disease-free survival (P < 0.001) during a median follow-up of 37.9 months with the hazard ratio for recurrence of 16.267 (95% confidence interval = 1.732–153.789; P = 0.015).MiRNA-196a level may be a promising prognostic marker of recurrence in resected PanNETs, although further experimental investigation would be required.     

Association of interleukin-6 gene polymorphisms with the risk of hepatocellular carcinoma: An up-to-date meta-analysis

Background:This study was aimed to evaluate the association between interleukin-6 (IL-6) gene polymorphisms and the risk of hepatocellular carcinoma (HCC) in a meta-analysis.Methods:A literature search was performed for case-control studies published during May, 1993 to May, 2020 focusing on IL-6 gene polymorphisms (–174G > C, –572G > C, and –597G > A) and HCC susceptibility by using PubMed, Cochrane Database, EMBASE, Web of science, and China National Knowledge Infrastructure. From 128 full-text articles, 11 were included in this meta-analysis. I² index was used to assess heterogeneity and Newcastle-Ottawa Scale was utilized for quality assessment.Results:For IL-6 –174G > C polymorphism, in codominant (GG vs CC: odds ratios [OR] = 2.78, 95% confidence intervals [CI] = 1.25–6.19, P = .01, I² = 16%) and recessive (GG+GC vs CC: OR = 2.76, 95% CI = 1.29–5.90, P = .009, I² = 3%) models, IL-6 –174G>C polymorphism was significantly associated with the risk of HCC. In dominant (GG vs CC+GC: OR = 1.80, 95% CI = 0.92–3.54, P = .09, I² = 86%) and allele (G vs C: OR = 1.49, 95% CI = 0.95–2.32, P = .08, I² = 68%) models, IL-6 –174G>C polymorphism had no impact on the risk of HCC. However, in non-Italian Caucasian population, IL-6 –174G>C polymorphism was significantly related to the occurrence of HCC in both dominant (GG vs CC+GC: OR = 3.26, 95% CI = 2.29–4.65, P < .00001, I² = 0%) and allele (G vs C: OR = 2.48, 95% CI = 1.48–4.15, P = .0006) models. Such correlations also could be observed when healthy individuals were selected as controls. For IL-6 –572G>C and –597G>A polymorphisms, no significant association was observed in all models, regardless of the source of control and population subgroups. No publication bias could be calculated when Begg and Egger tests were employed.Conclusion:This meta-analysis indicated that IL-6 –174G>C polymorphism was significantly related with the risk for HCC, especially in non-Italian Caucasian population. No significant association was observed for the correlation between IL-6 –572G>C and –597G>A polymorphisms and HCC susceptibility.     

Correlation between lncRNA SNHG16 gene polymorphism and its interaction with environmental factors and susceptibility to colorectal cancer

Objective:To study the relationship between long-chain non-coding RNA small nucleolar RNA host gene 16 (lncRNA SNHG16) polymorphisms and its interaction with environmental factors and susceptibility to colorectal cancer (CRC).Methods:Sanger sequencing was used to analyze genotypes of lncRNA SNHG16 gene rs7353, rs8038, and rs15278 sites. Multifactor dimensionality reduction was used to analyze interactions between lncRNA SNHG16 gene rs7353, rs8038, rs15278 sites, and environmental factors. Haploview 4.1 software was used to analyze linkage disequilibrium of lncRNA SNHG16 gene rs7353, rs8038, and rs15278 sites. Quantitative real-time polymerase chain reaction was used to analyze plasma lncRNA SNHG16 levels of CRC patients and control subjects.Results:Variation of the lncRNA SNHG16 gene rs7353 site A>G variation was associated with decreased CRC susceptibility (Odds ratio [OR] = 0.50, 95% confidence interval [CI]: 0.40–0.62, P < .01). The rs8038 site G>A and rs15278 site A>G variation were associated with increased CRC susceptibility (OR = 1.87, 95% CI: 1.47–2.36, P < .01). The rs15278 site G>A variation was associated with increased CRC susceptibility (OR = 2.24, 95% CI: 1.61–3.11, P < .01). Interaction combinations featuring age, rs7353, rs8038, and rs15278 single nucleotide polymorphism are 13.53 times more susceptible to CRC than other interactions (95% CI: 9.43–19.41, P < .01). The rs15278, rs8038, and rs7353 site AGA haplotypes were significantly associated with a decreased CRC risk (OR = 0.65, 95% CI: 0.48–0.88, P = .01), AAG haplotypes were significantly associated with an increased CRC risk (OR = 2.00, 95% CI: 1.27–3.17, P < .01). High lncRNA SNHG16 expression was associated with tumor progression in CRC patients (χ² = 8.85, P = .03). The rs7353 site A>G variation caused a significant decrease in plasma lncRNA SNHG16 level (P < .01), while the rs8038 site G>A variation and rs15278 site A>G variation resulted in increased plasma lncRNA SNHG16 levels.Conclusion:Polymorphisms of lncRNA SNHG16 gene rs7353, rs8038, rs15278 loci and their interaction with age are significantly associated with CRC susceptibility.     

Differential Expression of Hypertension-Associated MicroRNAs in the Plasma of Patients With White Coat Hypertension

White coat hypertension (WCH) is a high cardiovascular risk condition, and a fundamental understanding of the cause and pathophysiology of the disorder is still lacking. Recent studies demonstrated that microRNAs (miRNAs) are involved in hypertension; however, the roles of miRNAs in WCH are not known.The expressions of selected 10 miRNAs were investigated independently in plasma samples from 30 hypertension (HT) patients, 30 WCH patients, and 30 normotensive (NT) subjects.MiR-21, miR-122, miR-637, and let-7e expression levels were significantly upregulated in the HT group compared with the NT groups (P = 0.017, P = 0.022, P = 0.048, and P = 0.013, respectively). MiR-122 and miR-637 expressions were also significantly upregulated in the WCH group compared with the NT group (P = 0.048 and P = 0.039, respectively). MiR-296-5p expression level was significantly downregulated in HT patients and upregulated in the WCH patients compared with the NT group (P = 0.049 and P = 0.039, respectively).Additionally, the ambulatory 24-hour and daytime systolic and diastolic blood pressures were negatively correlated with miR-296-5p. MiR-296 and miR-637 had area under the curve (AUC) values of 0.778 and 0.774, respectively, which demonstrates their sufficiency to distinguish WCH from NT individuals. MiR-296 and miR-637 had AUC values of 0.868 and 0.680, respectively, which shows their potential to distinguish WCH from HT individuals.We report for the first time a plasma miRNA profile for WCH patients and demonstrate a novel link between miRNA and WCH. These findings may reveal crucial insights into the development of WCH.     

Genetic Association Studies Reporting on Variants in the C-Reactive Protein Gene and Coronary Artery Disease: A Meta-Analysis

C-reactive protein (CRP) is a commonly used inflammatory marker and elevated CRP levels are shown to increase the risk of coronary artery disease (CAD). Sequence variations in the CRP gene believed to influence the protein levels have been extensively investigated in CAD community. Most of the published studies, however, have reported mixed findings. The objective of the present study was to examine the associations of CRP variants (+942G>C, −717A>G, +1444C>T) with genetic risk of CAD by use of a meta-analysis.The human case–control studies were identified through online search, hand search, and contacting the authors of original articles. We performed both random-effect and fixed-effect meta-analysis to estimate CAD risk (odds ratios, OR). This analysis combined 16 studies in total. We found +942G>C was not associated with CAD risk when all data were pooled together, nor did we find a significant association in subgroup analyses. Meta-analysis of +1444C>T studies showed a similar trend. However, a borderline association with CAD risk was revealed for −717A>G (random-effect: OR = 0.53, 95% CI = 0.28–1.00 for the homozygous model; random-effect: OR = 0.51, 95% CI = 0.26–1.00 for the recessive model).These data suggest that the CRP gene variants examined may not modulate CAD risk.     

Machine-learning prediction of unplanned 30-day rehospitalization using the French hospital medico-administrative database

Predicting unplanned rehospitalizations has traditionally employed logistic regression models. Machine learning (ML) methods have been introduced in health service research and may improve the prediction of health outcomes. The objective of this work was to develop a ML model to predict 30-day all-cause rehospitalizations based on the French hospital medico-administrative database.This was a retrospective cohort study of all discharges in the year 2015 from acute-care inpatient hospitalizations in a tertiary-care university center comprising 4 French hospitals. The study endpoint was unplanned 30-day all-cause rehospitalization. Logistic regression (LR), classification and regression trees (CART), random forest (RF), gradient boosting (GB), and neural networks (NN) were applied to the collected data. The predictive performance of the models was evaluated using the H-measure and the area under the ROC curve (AUC).Our analysis included 118,650 hospitalizations, of which 4127 (3.5%) led to rehospitalizations via emergency departments. The RF model was the most performant model according to the H-measure (0.29) and the AUC (0.79). The performances of the RF, GB and NN models (H-measures ranged from 0.18 to 0. 29, AUC ranged from 0.74 to 0.79) were better than those of the LR model (H-measure = 0.18, AUC = 0.74); all P values <.001. In contrast, LR was superior to CART (H-measure = 0.16, AUC = 0.70), P < .0001.The use of ML may be an alternative to regression models to predict health outcomes. The integration of ML, particularly the RF algorithm, in the prediction of unplanned rehospitalization may help health service providers target patients at high risk of rehospitalizations and propose effective interventions at the hospital level.     

Upregulation of miRNA-130a Represents Good Prognosis in Patients With HBV-Related Acute-on-Chronic Liver Failure: A Prospective Study

Prompt and accurate prediction of the outcome is the key to make correct medical decision and to reduce the mortality in patients with HBV-related acute-on-chronic liver failure (ACLF). Increasing evidence have certified that small, noncoding microRNAs (miRNAs) play critically regulatory roles in the pathogenesis of liver diseases. However, it remains unclear whether and how miRNAs involve in the prognosis of ACLF.Microarray analysis was performed to characterize the miRNA expression profiles in liver tissues from 1 HBV-related ACLF patient and 1 matched healthy control. Nine miRNAs with at least 5 folds difference between these 2 persons were picked out. The present prospective study involving 39 HBV-related ACLF patients including 20 recovered and 19 nonrecovered patients, which include death (n = 9) and liver transplantation (n = 10). The serum expression of these miRNAs detected by quantitative real-time Polymerase Chain Reaction (qRT-RCR) was then compared between the 2 groups. Moreover, the correlation between the serum miRNAs and the prognostic indexes for ACLF was analyzed.The result of microarray analysis showed 9 miRNAs had different expression in liver tissues of ACLF patient compared with healthy control (upregulated: miRNA-130a, −21, −143, and −200a; downregulated: miRNA-486–5p, −192, −148a, −122, and −194). Unlike the expression profiles in liver tissue, 8 serum miRNAs except miRNA-194 were markedly upregulated in ACLF patients (P < 0.05). Remarkably, the serum expression of miRNA-130a and miRNA-486–5p was higher in recovered than nonrecovered ACLF patients (P < 0.05). Especially, the serum miRNA-130a was negatively correlated with international normalized ratio, prothrombin time, Model for End-Stage Liver Disease score, and positively correlated with prothrombin time activity. The AUC for recovered versus nonrecovered patients of miRNA-130a was 0.741 (P = 0.02).miRNA-130a might be a useful prognosis biomarker in patients with HBV-related ACLF.     

Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case–Control Studies

Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin-related myopathy risk remained controversial. This study aimed to investigate this genetic association.Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle–Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs).Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27–3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43–3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41–10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47–5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64–5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38–6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74–2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57–3.12, P = 0.52).The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of statin-related myopathy, especially in individuals receiving simvastatin. Thus, a genetic test before initiation of statins may be meaningful for personalizing the treatment.