Integrated analysis identifies S100A16 as a potential prognostic marker for pancreatic cancer.

BACKGROUND: The new S100 protein family member S100A16 is functionally expressed in various cancers. This study explored the prognostic value and potential role of S100A16 in pancreatic cancer (PC). METHODS: RNA-seq and clinical data were obtained from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA-PAAD) dataset to compare the expression level of S100A16 between groups. The genes co-expressed with S100A16 in TCGA-PAAD were analyzed using cBioPortal. Gene Ontology and Kyoto Encyclopedia of Genes and genomes enrichment analyses were also performed on these genes. Pathways related to S100A16 expression dysregulation were explored using gene set enrichment analysis. The Tumor Immune Estimation Resource was used to analyze the correlation between S100A16 and infiltrating immune cells. The Kaplan-Meier method and Cox analyses were used to assess the prognostic significance of S100A16 for PC. RESULTS: The S100A16 expression level was high in PC and increased with the degree of malignancy. The S100A16 functions in PC were mainly enriched in the immune modules, but negatively correlated with the immune activity (T-cell, cytokine, immune, co-receptor, signaling adaptor, cell adhesion molecule, chemokine, and JAK/STAT signaling) and infiltration level (T cells and macrophages). The strongest negative correlation was observed between the expression of CD8+ T cells and S100A16. Furthermore, high S100A16 expression also indicated worse overall survival and, therefore, worse prognosis of PC. CONCLUSION: S100A16 is a potential independent prognostic marker and immunotherapy target for PC. Mechanistically, S100A16 potentially affects prognosis by extensive immunosuppression, including the inhibition of the anti-tumor immune response of CD8+ T cells.

The Benefit and Safety of Aspirin for Primary Prevention of Ischemic Stroke: A Meta-Analysis of Randomized Trials.

Background: Although aspirin is effective in the secondary prevention of stroke among men and women, its use in primary prevention remains controversial. We conducted a meta-analysis of randomized trials to evaluate the benefit and safety of aspirin for the primary prevention of ischemic stroke. Methods: We searched three electronic databases (Medline, the Cochrane Central Register of Controlled Trials, and Embase) for articles published before August 1st, 2016. Randomized trials reporting the effect of aspirin on the primary prevention of ischemic stroke and its side effects (hemorrhagic stroke and severe gastrointestinal bleeding) were included. We used a fixed-effect model to quantify the effect of aspirin on the primary prevention of stroke when the heterogeneity was low, or else applied the random-effect model. Results: Fourteen randomized trials were included. Overall, aspirin use was associated with a decreased risk of ischemic stroke compared with non-aspirin use (OR: 0.83, 95% CI: 0.74-0.93, P = 0.45). In subgroup analyses, the effect of aspirin on ischemic stroke in apparently healthy adults remained significant (OR: 0.83, 95% confidence interval: 0.74-0.94, I2 = 22%, P = 0.28); while in patients with cardiovascular diseases there was no difference in the risk of ischemic stroke between aspirin and non-aspirin groups (OR: 0.75, 95% confidence interval: 0.44-1.29, P = 0.46). As for adverse effects, the prophylactic use of aspirin potentially increased the risk of serious bleeding events in a population of apparently healthy individuals and in patients with previous cardiovascular diseases. Conclusion: This meta-analysis of randomized trials indicated that both the apparently healthy adults and patients with cardiovascular diseases will derive little protective benefit from aspirin considering the increased risk of severe bleeding events.

Serum LncRNAs Profiles Serve as Novel Potential Biomarkers for the Diagnosis of HBV-Positive Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy that has a poor prognosis because there is lack of methods for early diagnosis. We aimed to utilize two serum long non-coding RNAs (lncRNAs), uc001ncr and AX800134, to diagnose hepatitis B virus (HBV)-positive HCC. METHODS: lncRNA microarrays were utilized to measure the differential expression of lncRNAs between tumor tissues and corresponding non-tumor tissues in HBV-positive hapatocellular carcinoma. uc001ncr and AX800134 were selected as candidate lncRNAs and detected in three independent cohorts containing a total of 684 participants (healthy individuals and chronic HBV patients and HBV-positive HCC patients) who were recruited between March 2011 and December 2012. A logistic regression model was constructed using a training cohort (n = 353) and validated using an independent cohort (n = 181). The area under the receiver operating characteristic curve (AUC) was utilized to evaluate the diagnostic accuracy. RESULTS: We determined that a panel based on the expression of uc001ncr and AX800134 accurately diagnosed HBV-positive HCC (AUC values of 0.9494 and 0.9491 for the training and validation cohorts, respectively). The diagnostic performance of the panel remained high in patients with AFP≤400 ng/ml (AUC values of 0.9371 and 0.9527 for the training and validation cohorts, respectively). The panel also diagnosed early HCC (AUC values of 0.9450 and 0.9564 for the training and validation cohorts, respectively). CONCLUSION: Our results indicated that the serum expression of uc001ncr and AX800134 has potential as novel potential biomarker for the diagnosis of HCC, especially in patients with AFP≤400 ng/ml or early-stage disease (BCLC 0+A).

Roles of fibroblast growth factor-inducible 14 in hepatocellular carcinoma.

The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressions in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson χ(2) test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy.

SHP-2 promoting migration and metastasis of MCF-7 with loss of E-cadherin, dephosphorylation of FAK and secretion of MMP-9 induced by IL-1beta in vivo and in vitro.

Shp-2, an src homology (SH) two-containing phosphotyrosine phosphatase, appears to be involved in cytoplasmic signaling downstream of a variety of cell surface receptors. It also plays an important role in the control of cell spreading, migration, and cytoskeletal architecture. In our study, abrogation of SHP-2 catalytic activity with a'dominant-negative mutant (SHP-2C > S) displayed an increased number of focal adhesion, high expression of E-cadhenrin and phosphorylation of the focal adhesion kinase (FAK). Interestingly, the cells expressing SHP-2C > S showed reduced IL-1beta-stimulated chemotaxis compared with either mock- or SHP-2 wild type-transfected cells. We also found that SHP-2-GFP-transfected cell lines did not express E-cadherin nearly and produced high level of the matrix metalloproteinase MMP-9 in the supernatants. The loss of E-cadherin-mediated adhesion and the increase of MMP-9-induced migration had been shown to play an important role in the transition of epithelial tumors from a benign to an invasive state. These findings have raised the possibility that SHP-2 can promote the cancer cell to invasion the distant tissues. To determine whether SHP-2 promotes invasion and metastasis, we transfected MCF-7 breast cancer cell lines with SHP-2-GFP, SHP-2C > S-GFP and analyzed the effects of the SHP-2 on cell migration, invasion, and metastasis. In vitro, SHP-2-GFP-transfected cells migrated more efficiently, showed an increased invasion of Matrigel, and adhered less efficiently to monolayers of fibroblast cells. When injected into the abdominal cavity of nude mice, SHP-2-GFP-transfected cells metastasized widely to the lung, kidney, but MCF-7 with SHP-2C > S-GFP was not observed in the these organs. These results demonstrate that SHP-2 promotes invasion and metastasis of MCF-7 with the loss of E-cadherin, the dephosphorylation of FAK and the secretion of MMP-9 induced by IL-1beta.

[Effects of the box-3 region of the LIFRalpha-chain cytoplasmic domain (gp190CT3) on the proliferation and differentiation of HL-60 cells].

OBJECTIVE: To study the effects of Box-3 region of the leukemia inhibitory factor receptor (LIFR) alpha-chain cytoplasmic domain on the proliferation and differentiation of HL-60 cells. METHODS: Expression vector of gp190CT3 was constructed and expressed in HL-60 cells. The expression level of gp190CT3 was assayed by immunocytochemistry. The growth of wild type and gp190CT3 transfected HL-60 cells were examined under microscope. The PCNA levels were assayed by Western blot, and the levels of CD15 by flow cytometry. RESULTS: The gp190CT3 transfected HL-60 cells were enlarged in size and their proliferation was slower than that of wild type. The expression level of PCNA was down-regulated while the level of CD15 up-regulated in transfected HL-60 cells as compared with that of the wild type cells. CONCLUSION: The Box-3 region of the leukemia inhibitory factor receptor alpha-chain cytoplasmic domain (gp190CT3) participates the LIFR signal transduction in inhibiting the growth and inducing the differentiation of HL-60 cells.