DNA methylation and miR-92a-3p-mediated repression of HIP1R promotes pancreatic cancer progression by activating the PI3K/AKT pathway.

Pancreatic cancer (PAAD) is a highly malignant tumour characterized of high mortality and poor prognosis. Huntingtin-interacting protein 1-related (HIP1R) has been recognized as a tumour suppressor in gastric cancer, while its biological function in PAAD remains to be elucidated. In this study, we reported the downregulation of HIP1R in PAAD tissues and cell lines, and the overexpression of HIP1R suppressed the proliferation, migration and invasion of PAAD cells, while silencing HIP1R showed the opposite effects. DNA methylation analysis revealed that the promoter region of HIP1R was heavily methylated in PAAD cell lines when compared to the normal pancreatic duct epithelial cells. A DNA methylation inhibitor 5-AZA increased the expression of HIP1R in PAAD cells. 5-AZA treatment also inhibited the proliferation, migration and invasion, and induced apoptosis in PAAD cell lines, which could be attenuated by HIP1R silencing. We further demonstrated that HIP1R was negatively regulated by miR-92a-3p, which modulates the malignant phenotype of PAAD cells in vitro and the tumorigenesis in vivo. The miR-92a-3p/HIP1R axis could regulate PI3K/AKT pathway in PAAD cells. Taken together, our data suggest that targeting DNA methylation and miR-92a-3p-mediated repression of HIP1R could serve as novel therapeutic strategies for PAAD treatment.

Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis.

Many noninvasive methods for diagnosing liver fibrosis (LF) have been proposed. To determine the best method for diagnosing LF in nonalcoholic fatty liver disease (NAFLD), we conducted a systemic review and meta-analysis to compare the performance of aspartate aminotransferase to platelets ratio index (APRI), fibrosis-4 index (FIB-4), BARD score, NAFLD fibrosis score (NFS), FibroScan, shear wave elastography (SWE), and magnetic resonance elastography (MRE) for diagnosing LF in NAFLD. We compared the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUROC) of these noninvasive methods for detecting significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis. Heterogeneity was explored using meta-regression. Sixty-four articles with a total of 13,046 NAFLD subjects were included. The overall mean prevalence of SF, AF, and cirrhosis was 45.0%, 24.0%, and 9.4% in NAFLD patients, respectively. With an APRI threshold of 1.0 and 1.5, the sensitivities and specificities were 50.0% and 84.0% and 18.3% and 96.1%, respectively, for AF. With a FIB-4 threshold of 2.67 and 3.25, the sensitivities and specificities were 26.6% and 96.5% and 31.8% and 96.0%, respectively, for AF. The summary sensitivities and specificities of BARD score (threshold of 2), NFS (threshold of -1.455), FibroScan M (threshold of 8.7-9), SWE, and MRE for detecting AF were 0.76 and 0.61, 0.72 and 0.70, 0.87 and 0.79, 0.90 and 0.93, and 0.84 and 0.90, respectively. The summary AUROC values using APRI, FIB-4, BARD score, NFS, FibroScan M probe, XL probe, SWE, and MRE for diagnosing AF were 0.77, 0.84, 0.76, 0.84, 0.88, 0.85, 0.95, and 0.96, respectively. CONCLUSION: MRE and SWE may have the highest diagnostic accuracy for staging fibrosis in NAFLD patients. Among the four noninvasive simple indexes, NFS and FIB-4 probably offer the best diagnostic performance for detecting AF. (Hepatology 2017;66:1486-1501).

Transcatheter arterial chemoembolization of apatinib and camrelizumab (SHR1210) against liver metastasis from hepatic neuroendocrine tumor: a case report.

In this case report, we present the case of a 46-year-old woman with a hepatic neuroendocrine tumor (NET G2)-induced liver metastases. Initially, the left lateral lobectomy of the liver was performed. The post-operative pathological examination revealed NET G2, leading to the post-operative recovery with a general review. Further, the re-examination of liver magnetic resonance imaging (MRI) showed post-operative changes in the tumor of the left lateral lobe, with multiple liver masses and possible metastasis. Thus, the liver interventional therapy and apatinib-based targeted therapy based on the "camrelizumab + apatinib" regimen were performed, respectively. The 20-month follow-up indicated a slightly increased hepatic hilum and retroperitoneal lymph nodes, accompanied by hand-foot syndrome. Eventually, the overall condition continued to relieve, indicating that the combined treatment could substantially improve the NET G2 conditions-associated liver metastasis.

CAF-derived exosomal lncRNA FAL1 promotes chemoresistance to oxaliplatin by regulating autophagy in colorectal cancer.

Oxaliplatin is a widely applied anti-cancer drug in clinics for colorectal cancer (CRC) treatment. Nonetheless, the treatment efficacy is always limited by the acquisition of chemoresistance in cancer cells. The deregulation of long non-coding RNA (lncRNA) FAL1 has been implicated in the tumorigenesis and progression of different malignancies. Nevertheless, the possible contribution of lnc-FAL1 in drug resistance development of CRC has not been investigated. Here, we reported the overexpression of lnc-FAL1 in CRC samples, and elevated lnc-FAL1 levels seemed to be associated with the poor survival in CRC patients. We further demonstrated that lnc-FAL1 promoted oxaliplatin chemoresistance in both cell and animal model. Additionally, lnc-FAL1 was mainly derived from exosomes secreted by cancer associated fibroblasts (CAFs), and lnc-FAL1-containing exosomes or lnc-FAL1 overexpression significantly inhibited oxaliplatin-induced autophagy in CRC cells. Mechanistically, lnc-FAL1 acted as a scaffold for the interaction between Beclin1 and TRIM3 to promote TRIM3-dependent Beclin1 polyubiquitination and degradation, thereby suppressing oxaliplatin-induced autophagic cell death. In summary, these data imply a molecular mechanism through which CAF-derived exosomal lnc-FAL1 contributes to the acquisition of oxaliplatin resistance in CRC.

Identification of the Roles of Chromobox Family Members in Gastric Cancer: A Study Based on Multiple Datasets.

BACKGROUND: As the important components in polycomb repressive complexes 1 (PRC1) and heterochromatin protein 1 (HP1), Chromobox (CBX) family members are involved in epigenetic regulatory function, transcriptional repression, and other cellular metabolisms. Increasing studies have indicated significant associations between CBX and tumorigenesis, which is a progression in different types of cancers. However, the information about the roles of each CBX in gastric cancer is extremely limited. METHODS: We explored CBX mRNA expression, corrections with clinicopathological parameters, protein expression, prognostic values, enrichment analysis with several databases including Oncomine, Human Protein Atlas, UALCAN, Kaplan-Meier plotter, cBioPortal, GeneMANIA, and Enrichr. RESULTS: In our study, comparing to the normal tissues, higher mRNA expression of CBX1/2/3/4/5/8 and lower mRNA expression of CBX7 were found in GC tissues while upregulations of CBX1/2/3/4/5/8 and downregulations of CBX7 were indicated to be significantly correlated to the nodal metastasis status and individual cancer stages in GC patients. As for protein level, the expression of CBX2/3/4/5/6 was higher and the expression of CBX7 was lower in the GC tissues than those in the normal. What is more, higher mRNA expression of CBX1/5/6/8 and lower mRNA expression of CBX7 were markedly correlated to poor outcomes of OS and FP in GC patients. Besides, high mutation rate of CBXs (42%) was observed in GC patients. CONCLUSIONS: We suggest that CBX5/7 may serve as potential therapeutic targets for GC while CBX1/8 may serve as potential prognostic indicators for GC.

Prognostic and clinicopathologic significance of neutrophil-to-lymphocyte ratio in esophageal squamous cell carcinoma: evidence from a meta-analysis.

PURPOSE: Evidence from an increasing number of studies has demonstrated that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor for various cancers. However, it is unclear whether NLR predicts prognosis in esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis to investigate the prognostic and clinicopathologic significance of NLR in patients with ESCC. PATIENTS AND METHODS: Selected studies were identified by searches in PubMed, Embase, and Web of Science databases and filtered using our prepared criteria. The hazard ratio (HR) and odds ratio were chosen as effect measures to assess the prognostic role of NLR and its clinicopathologic significance in ESCC. In total, nine studies containing 2,513 patients were enrolled. RESULTS: We demonstrated that elevated NLR was associated with worse overall survival in ESCC patients (pooled HR =1.314; 95% confidence interval, 1.164-1.484; P<0.001). Elevated NLR was also associated with unfavorable characteristics regarding depth of tumor invasion, tumor size, clinical stage, and differentiation degree. CONCLUSION: The results of our meta-analysis suggest that a high NLR value might represent a poor prognosis and worse clinicopathologic characteristics for patients with ESCC.