Piwi-like protein 2 (Piwil2) has recently emerged as a putative oncogene which is amplified in several human malignancies. However, the role of Piwil2 in colon cancer remains poorly understood. The aim of this study was to investigate the clinical and pathological significance of Piwil2, and the possible role in the proliferation and metastasis of colon cancer. Primary colon cancer paired with adjacent normal colon tissue and lymph node metastasis (LNM) lesions in 66 patients' tissue microarrays (TMA) were used to determine the expression of Piwil2. Knocked down Piwil2 expression in SW620 and SW480 colon cancer cell lines was performed to evaluate the role of Piwil2 in cell proliferation, invasion, metastasis in vitro and tumorigenicity in vivo. The possible roles of Piwil2 in the regulation of a 2 kb matrix metallopeptidase 9 (MMP9) promoter fragment and on the regulation of apoptotic pathways were evaluated by using a luciferase reporter construct and Western blots, respectively. Significantly higher expression levels of Piwil2 were observed in primary colon cancer tissue and in LNM in comparison with normal colon mucosa. Piwil2 expression significantly correlated with more aggressive clinical and pathological parameters with poorer five-year metastasis-free survival and overall survival. Piwil2 silencing significantly reduced cancer cell proliferation, colony formation ability and increased apoptosis in vitro and inhibited tumor growth in vivo. Piwil2 knockdown also attenuated migration and invasion of colon cancer cells via modulation of MMP9 transcriptional activities. Our results indicate that Piwil2 moderates the proliferation and metastasis potential of colon cancer.
BackgroundThis study aimed to determine whether community-acquired pneumonia (CAP) had a metabolic profile and whether this profile can be used for disease severity assessment.MethodsA total of 175 individuals including 119 CAP patients and 56 controls were enrolled and divided into two cohorts. Serum samples from a discovery cohort (n = 102, including 38 non-severe CAP, 30 severe CAP, and 34 age and sex-matched controls) were determined by untargeted ultra-high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomics. Selected differential metabolites between CAP patients versus controls, and between the severe CAP group versus non-severe CAP group, were confirmed by targeted mass spectrometry assays in a validation cohort (n = 73, including 32 non-severe CAP, 19 severe CAP and 22 controls). Pearson’s correlation analysis was performed to assess relationships between the identified metabolites and clinical severity of CAP. The area under the curve (AUC), sensitivity and specificity of the metabolites for predicting the severity of CAP were also investigated.ResultsThe metabolic signature was markedly different between CAP patients and controls. Fifteen metabolites were found to be significantly dysregulated in CAP patients, which were mainly mapped to the metabolic pathways of sphingolipid, arginine, pyruvate and inositol phosphate. The alternation trends of five metabolites among the three groups including sphinganine, p-Cresol sulfate, dehydroepiandrosterone sulfate (DHEA-S), lactate and l-arginine in the validation cohort were consistent with those in the discovery cohort. Significantly lower concentrations of sphinganine, p-Cresol sulfate and DHEA-S were observed in CAP patients than in controls (p < 0.05). Serum lactate and sphinganine levels were positively correlated with confusion, urea level, respiratory rate, blood pressure, and age > 65 years (CURB-65), pneumonia severity index (PSI) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, while DHEA-S inversely correlated with the three scoring systems. Combining lactate, sphinganine and DHEA-S as a metabolite panel for discriminating severe CAP from non-severe CAP exhibited a better AUC of 0.911 (95% confidence interval 0.825–0.998) than CURB-65, PSI and APACHE II scores.ConclusionsThis study demonstrates that serum metabolomics approaches based on the LC-MS/MS platform can be applied as a tool to reveal metabolic changes during CAP and establish a metabolite signature related to disease severity.Trial registrationClinicalTrials.gov, NCT03093220. Registered retrospectively on 28 March 2017.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2049-2) contains supplementary material, which is available to authorized users.
BackgroundCommunity-acquired pneumonia (CAP) is a major cause of death worldwide and occurs with variable severity. There are few studies focused on the expression of soluble urokinase-type plasminogen activator receptor (suPAR) and syndecan-4 in patients with CAP.MethodsA prospective, multi-centre study was conducted between January 2014 and December 2016. A total of 103 patients with severe CAP (SCAP), 149 patients with non-SCAP, and 30 healthy individuals were enrolled. Clinical data were recorded for all enrolled patients. Serum suPAR and syndecan-4 levels were determined by quantitative enzyme-linked immunosorbent assay. The t test and Mann–Whitney U test were used to compare between two groups; one-way analysis of variance and the Kruskal–Wallis test were used to compare multiple groups. Correlations were assessed using Pearson and Spearman tests. Area under the curve (AUCs), optimal threshold values, sensitivity, and specificity were calculated. Survival curves were constructed and compared by log-rank test. Regression analyses assessed the effect of multiple variables on 30-day survival.ResultssuPAR levels increased in all patients with CAP, especially in severe cases. Syndecan-4 levels decreased in patients with CAP, especially in non-survivors. suPAR and syndecan-4 levels were positively and negatively correlated with severity scores, respectively. suPAR exhibited high accuracy in predicting SCAP among patients with CAP with an AUC of 0.835 (p < 0.001). In contrast, syndecan-4 exhibited poor diagnostic value for predicting SCAP (AUC 0.550, p = 0.187). The AUC for predicting mortality in patients with SCAP was 0.772 and 0.744 for suPAR and syndecan-4, respectively; the respective prediction threshold values were 10.22 ng/mL and 6.68 ng/mL. Addition of both suPAR and syndecan-4 to the Pneumonia Severity Index significantly improved their prognostic accuracy, with an AUC of 0.885. Regression analysis showed that suPAR ≥10.22 ng/mL and syndecan-4 ≤ 6.68 ng/mL were reliable independent markers for prediction of 30-day survival.ConclusionsuPAR exhibits high accuracy for both diagnosis and prognosis of SCAP. Syndecan-4 can reliably predict mortality in patients with SCAP. Addition of both suPAR and syndecan-4 to a clinical scoring method could improve prognostic accuracy.Trial registrationClinicalTrials.gov, NCT03093220. Registered on 28 March 2017 (retrospectively registered).
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