Purpose: The correlation between patatin-like phospholipase domain-containing protein 3 ( PNPLA3) rs738409 polymorphism and hepatocellular carcinoma was investigated by several pilot studies, but the results of these studies were controversial. Therefore, we performed this study to better assess the relationship between PNPLA3 rs738409 polymorphism and the likelihood of hepatocellular carcinoma. Methods: Eligible studies were searched in PubMed, Medline, EMBASE, and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between PNPLA3 rs738409 polymorphism and hepatocellular carcinoma. Results: A total of 17 studies with 10,330 participants were analyzed. A significant association with the likelihood of hepatocellular carcinoma was detected for the PNPLA3 rs738409 polymorphism in dominant ( P = 0.0001; OR 0.66; 95% CI 0.53, 0.82), recessive ( P < 0.0001; OR 2.32; 95% CI 1.76, 3.06) and allele ( P < 0.0001; OR 0.64; 95% CI 0.53, 0.77) comparisons. Further subgroup analyses revealed that the PNPLA3 rs738409 polymorphism was significantly associated with the likelihood of hepatocellular carcinoma in Caucasians (dominant model: P < 0.0001, OR 0.57, 95% CI 0.45, 0.71; recessive model: P < 0.0001, OR 2.74, 95% CI 2.02, 3.71; allele model: P < 0.0001, OR 0.56, 95% CI 0.46, 0.67). However, no positive results were detected in Asians. Conclusions: Our findings indicated that the PNPLA3 rs738409 polymorphism may serve as a potential biological marker of hepatocellular carcinoma in Caucasians.
Abnormal immune cell infiltration is associated with the pathogenesis of Crohn’s disease (CD). This study aimed to determine the diagnostic and predictive value of immune-related genes in CD. Seven Gene Expression Omnibus datasets that analyzed the gene expression in CD tissues were downloaded. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate the infiltration of the immune cells in CD tissues. Immune-related genes were screened by overlapping the immune-related genes with differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to identify key immune-related DEGs. Diagnostic value of CD and predictive value of anti-TNFα therapy were analyzed. Immunohistochemical (IHC) assay was used to verify gene expression in CD tissues. There were significant differences among CD tissues, paired CD tissues, and normal intestinal tissues regarding the infiltration of immune cells. AQP9, CD27, and HVCN1 were identified as the key genes of the three sub-clusters in the PPI network. AQP9, CD27, and HVCN1 had mild to moderate diagnostic value in CD, and the diagnostic value of AQP9 was better than that of CD27 and HVCN1. AQP9 expression was decreased in CD after patients underwent anti-TNFα therapy, but no obvious changes were observed in non-responders. AQP9 had a moderate predictive value in patients who had undergone treatment. IHC assay confirmed that the expression of AQP9, CD27, and HVCN1 in CD tissues was higher than that in normal intestinal tissues, and AQP9, CD27 was correlated with the activity of CD. Immune-related genes, AQP9, CD27, and HVCN1 may act as auxiliary diagnostic indicators for CD, and AQP9 could serve as a promising predictive indicator in patients who underwent anti-TNF therapy.
Interleukin-10 (IL-10) is a key anti-inflammatory cytokine, and it is associated with the pathogenesis of inflammatory bowel disease (IBD). However, the relationship between serum IL-10 level and IBD remains controversial. In this study, a meta-analysis was performed using STATA 12.0 software. Articles were gathered by searching PubMed, Web of Science, Embase, and the Chinese Biomedical Database. Relevant studies were examined to identify their eligibility. Finally, eight studies met the inclusion criteria; these studies consisted of 211 patients diagnosed with ulcerative colitis (UC), 134 patients diagnosed with Crohn's disease (CD), and 131 healthy control subjects. The IL-10 levels in the serum samples of UC patients significantly increased (pooled standardized mean difference (SMD) = 0.55, 95% confidence interval (CI): 0.08-1.03, P = 0.022). No significant association was observed in both adult (>17 years old) and pediatric (<17 years old) UC patients in a subgroup analysis performed in terms of age among all UC patients. The relationship between serum IL-10 concentration and UC patients did not differ as determined by enzyme-linked immunosorbent assay (ELISA), and no significant differences were observed when Bio-Plex technology and Luminex assay were used for analyses. There is no statistical difference of serum IL-10 levels between patients with UC and CD. Results suggest that the IL-10 levels increased in UC patients compared with the control group, and such increase contributes to the pathogenesis and progression of UC. Therefore, serum IL-10 level may be a noninvasive biomarker for UC patients.
Background. The role of miR-200c in gastric cancer remains controversial. This study is aimed at clarifying the diagnostic and prognostic value of miR-200c in gastric cancer through a meta-analysis. Methods. A comprehensive literature search of PubMed, Embase, and Ovid library databases was conducted. The studies included were those conducted before December 2017. The sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under curve (AUC) were used to estimate the diagnostic value of miR-200c. Meanwhile, the pooled hazard ratio (HR) was used to estimate the prognostic value of miR-200c. Results. For the diagnostic value of miR-200c, six studies that included 202 patients with gastric cancer and 250 normal controls were analyzed. The sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.74, 0.66, 2.20, 0.40, 5.34, and 0.75, respectively. Subgroup analysis showed no significant difference in the type of the sample, method for testing miR-200c, and ethnicity among the patients. Meanwhile, for the prognostic value of miR-200c, seven studies comprising 935 patients with gastric cancer were analyzed. The pooled results showed that miR-200c expression was associated with overall survival (HR=2.19) and disease-free survival (HR=1.73), but not with progression-free survival (HR=1.64) in patients with gastric cancer. There was no publication bias across the studies. Conclusions. Both serum and tissue miR-200c have moderate diagnostic accuracy in gastric cancer. miR-200c could also be used as a valuable indicator for predicting the prognosis of gastric cancer patients.
Background: During endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), cytopathology with rapid on-site evaluation (ROSE) can improve diagnostic yield and accuracy. However, ROSE is unavailable in most Asian and European institutions because of the shortage of cytopathologists. Therefore, developing computer-assisted diagnostic tools to replace manual ROSE is crucial. Herein, we reported the validation of an artificial intelligence (AI)-based model (ROSE-AI model) to substitute manual ROSE during EUS-FNA. Methods: A total of 467 digitized images from Diff-Quik (D&F)-stained EUS-FNA slides were divided into training (3642 tiles from 367 images) and internal validation (916 tiles from 100 images) datasets. The ROSE-AI model was trained and validated using training and internal validation datasets, respectively. The specificity was emphasized while developing the model. Then, we evaluated the AI model on a 693-image external dataset. We assessed the performance of the AI model to detect cancer cells (CCs) regarding the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results:The ROSE-AI model achieved an accuracy of 83.4% in the internal validation dataset and 88.7% in the external test dataset. The sensitivity and PPV were 79.1% and 71.7% in internal validation dataset and 78.0% and 60.7% in external test dataset, respectively. Conclusion:We provided a proof of concept that AI can be used to replace manual ROSE during EUS-FNA. The ROSE-AI model can address the shortage of cytopathologists and make ROSE available in more institutes.Guo and Xin Ling helped collect data. Rong-Gan Wei classified images and annotated CCs. All authors read and approved the manuscript.
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