Diagnostic and prognostic potentials of microRNA-27a in osteosarcoma

AimGrowing evidence suggest that the microRNA (miR)-23a/24-2/27a cluster may play a crucial role in mammary tumorigenesis and act as a novel class of oncogenes. Among these members, miR-27a has been reported to promote proliferation, migration and invasion in human osteosarcoma cells. The aim of this study was to detect the serum levels of miR-27a in osteosarcoma patients and to investigate its associations with clinicopathological features and prognosis.MethodsmiR-27a levels in sera from 166 osteosarcoma patients and 60 healthy controls were detected by real-time quantitative RT-PCR. Then, the associations of serum miR-27a level with clinicopathological factors or survival of osteosarcoma patients were further evaluated.ResultsCompared to healthy controls, the serum levels of miR-27a were significantly increased in osteosarcoma patients (P < 0.001). Importantly, miR-27a could efficiently screen osteosarcoma patients from healthy controls (Area under receiver operating characteristic curve, AUC = 0.867). Then, high miR-27a expression was more frequently occurred in osteosarcoma patients with advanced clinical stage (P = 0.001), positive distant metastasis (P = 0.01) and poor response to chemotherapy (P = 0.008). In Kaplan–Meier survival analysis, high miR-27a expression was a significant indicator for poor overall survival (P = 0.006) as well as poor disease-free survival (P = 0.01). Furthermore, multivariate analysis demonstrated that miR-27a expression was an independent and significant prognostic factor to predict overall survival (P = 0.01) and disease-free survival (P = 0.03).ConclusionmiR-27a expression may be elevated in sera of osteosarcoma patients and in turn contributes to aggressive progression of this malignancy. Detection of serum miR-27a levels may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients.     

Prognostic value of miR-26a and HMGA1 in urothelial bladder cancer

BackgroundMicroRNA-26a (miR-26a) functions as a tumor suppressor by regulating its direct target gene high mobility group AT-hook 1 (HMGA1). This study was aimed to investigate the associations of differential expression of miR-26a and HMGA1 with tumor progression and prognosis in urothelial bladder cancer (UBC) patients.Materials and methodsOne hundred and twenty-six UBC patients were selected and quantitative real-time PCR was performed to detect the expression of miR-26a and HMGA1 mRNA in the respective tumors.ResultsOur data showed the decreased expression of miR-26a and the increased expression of HMGA1 mRNA in UBC tissues compared with corresponding non-cancerous tissues (both P < 0.001). Then, the expression levels of miR-26a in UBC tissues were negatively correlated with those of HMGA1 mRNA significantly (r = –0.72, P < 0.001). In addition, UBC patients with combined miR-26a downregulation and HMGA1 upregulation (miR-26a-low/HMGA1-high) more frequently had advanced pathological stage (P < 0.001) and high tumor grade (P < 0.001). Moreover, miR-26a-low/HMGA1-high expression was associated with a significantly shortest disease-free survival (P < 0.001) and overall survival (P < 0.001) of all miR-26a/HMGA1 combined expression groups. Furthermore, multivariate analysis indicated that miR-26a/HMGA1 expression was an independent prognostic factor for both disease-free survival and overall survival (both P = 0.001) in UBC patients.ConclusionInteraction between miR-26a and its target gene HMGA1 may contribute to the malignant progression of human UBC. Tumors with miR-26a downregulation in combination with high expression of HMGA1 showed a worse prognosis than the other tumors. Combined detection of their expression might be particularly helpful for surveillance of disease progression and treatment stratification.     

Decreased expression of microRNA-148a predicts poor prognosis in ovarian cancer and associates with tumor growth and metastasis

ObjectiveMicroRNA-148a (MiR-148a) had been reported to take part in some cancer progresses, but its clinical significance in ovarian cancer had been rarely reported. The purpose of this study was to evaluate the prognostic value of miR-148a as well as its roles in ovarian cancer progression.MethodsRelative expression of miR-148a in the plasma specimens of ovarian cancer patients was detected by qRT-PCR. Chi-square test was used to analyze the relationship between miR-148a expression and clinical characteristics. The overall survival was analyzed by Kaplan-Meier method and Cox regression analysis was used to evaluate the prognostic value of miR-148a. In addition, the ovarian cancer cell line SKOV-3 was separately transfected with pcDNA3-microRNA-148a over-expression vector and pcDNA3 empty vector to detect the functional roles of miR-148a in ovarian cancer progression.ResultsDecreased level of plasma miR-148a was observed in ovarian cancer patients compared with healthy controls. The expression level was associated with histopathologic grade, TNM stage and lymph node metastasis (P < 0.05 for all). Besides, patients with high level of miR-148a had a longer survival time than those with low level (40.3 months vs 31.6 months, log rank test, P = 0.002). Cox regression analysis indicated that miR-148a might be a potential biomarker for ovarian cancer prognosis (HR = 1.699, 95%CI = 1.175-2.456, P = 0.005). Moreover, cell experiments confirmed that miR-148a could inhibit proliferation, migration and invasion of ovarian cancer cells.ConclusionMiR-148a may be a potential prognostic factor for ovarian cancer and it can suppress tumor progression.     

Fluvastatin combined with benazepril may contribute to the favorable prognosis of patients with atrial fibrillation

The aim of this study was to observe the clinical efficacy of fluvastatin combined with benazepril in the treatment of patients with atrial fibrillation (AF). A total of 92 patients with AF were randomly assigned to the case group (n = 46), in which the patients were treated with fluvastatin (80 mg) plus benazepril (10 mg), or to the control group (n = 46), in which the patients were treated with fluvastatin (80 mg). The conversion rate of sinus rhythm was higher in the case group than in the control group (P < 0.05). The case group had more treatment-effective patients than the control group, with fewer treatment-ineffective patients (P < 0.05). The LVEDd, LVESd, LAD, and LVEF indexes in the case group were lower than in the control group after 6 months of treatment (all P < 0.05). Levels of hs-CRP were also lower in patients in the case group than in patients in the control group after 1 month of treatment (P < 0.05). After 12 months, renin and Ang II concentrations were lower in patients in the case group than in the control group (both P < 0.05). Significant differences in IL-6 and TNF-α expression were found between the two groups after 1 month, 6 months, and 12 months of treatment (all P < 0.05). Compared to patients in the control group, the levels of total cholesterol (TC), triglycerides, and LDL-C in the case group were lower after 6 and 12 months of treatment (all P < 0.05), while the HDL level was higher (P < 0.05). Treatment with fluvastatin combined with benazepril further increased the conversion rate of sinus rhythm and significantly improved the quality of life and prognosis of AF patients.     

Clinical significance of serum M30 and M65 levels in patients with breast cancer

M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin18. The objective of this study was to determine the clinical significance of the serum levels of M30 and M65 in patients with breast cancer. A total of 80 patients with a pathologically confirmed diagnosis of breast cancer were enrolled into the study. Serum M30 and M65 concentrations were determined by the solid-phase sandwich ELISA method. Serum samples were obtained on first admission before any type of treatment. The median age at diagnosis was 52 years, range 30 to 81 years. The baseline serum M30 and M65 levels in patients with metastatic disease were significantly higher than those in the non-metastatic patients (P = 0.017 and P = 0.003, respectively). Moreover, serum M65 level was also elevated in patients with large tumor size (P = 0.02). No correlation was found between these serum assay levels and response to chemotherapy (P > 0.05). However, the significant relationship was found between the serum levels of M30 and M65 (r_s = 0.96, P < 0.001). Neither serum M30 nor serum M65 had significantly effect on survival (P = 0.50, and P = 0.52, respectively). In conclusion, although both serum M30 and M65 levels are elevated in metastatic disease, no predictive and prognostic roles on survival were found in patients with breast cancer.     

Effect of a high-intensity interval training on serum microRNA levels in women with breast cancer undergoing hormone therapy. A single-blind randomized trial

BackgroundThe role of microRNAs (miRs) in hormone therapy (HT) is of keen interest in developing biomarkers and treatments for individuals with breast cancer. Although miRs are often moderate regulators under homeostatic conditions, their function is changed more in response to physical activity.ObjectiveThis single-blind randomized trial aimed to explore the effect of high-intensity interval training (HIIT) on serum levels of miRs in individuals with early-stage breast cancer undergoing HT.MethodsHormone receptor-positive women with breast cancer and healthy women were randomly assigned to a healthy control group (n = 15), healthy group with HIIT (n = 15), breast cancer group with HT (HT, n = 26), and breast cancer group with HT and HIIT (HT + HIIT, n = 26). The exercise groups underwent interval uphill walking training on a treadmill 3 times a week for 12 weeks. At the end of the study, we analyzed changes in levels of cancer-related miRs (oncomiRs) and tumour suppressor miRs (TSmiRs) in response to the HT and HIIT.ResultsIn women with breast cancer versus healthy controls, the expression of some oncomiRs was significantly increased — miR-21 (P < 0.001), miR-155 (P = 0.001), miR-221 (P = 0.008), miR-27a (P < 0.001), and miR-10b (P = 0.007) — and that of some TSmiRs was significantly decreased — miR-206 (P = 0.048), miR-145 (P = 0.011), miR-143 (P = 0.008), miR-9 (P = 0.020), and let-7a (P = 0.005). Moreover, HT considerably downregulated oncomiRs and upregulated TSmiRs. HIIT for 12 weeks with HT significantly decreased the expression of the oncomiRs and significantly increased that of the TSmiRs as compared with HT alone.ConclusionsHITT could amplify the decrease and/or increase in expression of miRs associated with HT in women with breast cancer. A prospective trial could determine whether the use of circulating miRs for monitoring treatment can be useful in therapy decisions.Trial registrationIranian Registry of Clinical Trials (No.: IRCT201202289171N1).     

The prognostic value of serum pregnancy-associated plasma protein A,S100 and high sensitivity C-reactive protein in acute ischemic stroke patients without heparin administration

ObjectivesThe concerns regarding the pre-analytical bias caused by medicine treatments have been raised in the diagnosis and prognosis of ischemic stroke recently. The aim of this study was to examine the prognostic value of serum pregnancy-associated plasma protein A (PAPP-A), S100 and high sensitivity C-reactive protein (hs-CRP) in heparin-naïve patients of acute ischemic stroke.Design and methodsSerum levels of PAPP-A, S100 and hs-CRP were determined in 205 heparin-naïve patients of acute ischemic stroke and 50 healthy controls. Clinical information and radiological information were collected. Unfavorable outcomes (stroke recurrence, myocardial infarction or death) were also recorded after six months. The associations between serum biomarker levels and stroke severity/outcome were assessed.ResultsSerum PAPP-A, S100 and hs-CRP levels increased in patients compared with controls (P < 0.05). S100 and hs-CRP levels were significantly higher in patients with larger cerebral infarction sizes (P < 0.05) and more severe neurological impairment (P < 0.05). Serum PAPP-A level showed a progressive increase with the increase of stroke severity (P < 0.05). Serum hs-CRP and National Institutes of Health Stroke Scale (NIHSS) scores were identified as independent predictors for unfavorable outcomes with odds ratios of 2.884 (1.154 to 7.210, P = 0.023) and 2.887 (1.146 to 7.273, P = 0.024), respectively.ConclusionSerum PAPP-A, S100 and hs-CRP were associated with stroke severity or outcome after ischemic stroke and may offer complementary information, essential for clinical decision making. Serum PAPP-A showed a potential value for the evaluation of stroke clinically.     

The expression of TSSC3 and its prognostic value in patients with osteosarcoma

Osteosarcoma is one of the most common primary bone tumors in children and adolescents, typically presenting with poor prognosis. Recent studies have found that TSSC3 had a potential capability in suppressing the tumor development in osteosarcoma. Our purpose was to explore the role of TSSC3 in the clinical outcome of osteosarcoma patients. Firstly, we detected the expression of TSSC3 at mRNA level by quantitative real-time polymerase chain reaction (qRT-PCR). The result demonstrated that TSSC3 expression was lower in osteosarcoma patients than in healthy controls (P < 0.05). Then, the relationship between TSSC3 and clinicopathological characteristics was analyzed by chi-square test which manifested that WHO grade, metastasis, and recurrence were vital influential factors on the expression of TSSC3 (P < 0.05). We also estimated the association between TSSC3 and overall survival of osteosarcoma patients by Kaplan–Meier analysis as well as assessed the prognostic value of TSSC3 and clinicopathological characteristics through cox regression analysis. Patients with high TSSC3 expression were proved to live longer than those with low TSSC3 expression (log rank test, P < 0.05). TSSC3 expression (P = 0.032, HR = 0.405, 95%CI = 0.177–0.926) and metastasis (P = 0.010, HR = 2.849, 95%CI = 1.291–6.287) were considered to be independent prognostic factors in osteosarcoma. Taken together, our findings provided preliminary evidence that the TSSC3 was a prognostic marker in osteosarcoma and this might be useful for the therapy of osteosarcoma.     

Soluble P selectin in synovial fluid level is correlated with the radiographic severity of knee osteoarthritis

BackgroundRecent studies provide evidence that inflammation is a feature of the disease process in Osteoarthritis (OA). The clinical significance of P selectin (Ps) in OA has not been adequately studied and the association between Ps level and OA severity remains unknown.MethodsWe enrolled 120 knee OA subjects and 45 controls. All patients were scored for Kellgren–Lawrence grade (0–4). The Ps in serum and synovial fluid (SF) as well as serum C-reactive protein (CRP) levels were detected.ResultsThe mean Ps level in OA subjects was markedly increased than that in controls. In OA patients, the SF Ps levels increased with the severity of KL scores and significantly correlated with severity of disease (r = 0.546, P < 0.001) and serum CRP level (r = 0.488, P < 0.001). However, the serum Ps level did not show a significant correlation with the severity of OA.ConclusionThe Ps levels in SF were significantly correlated with the severity of OA, suggesting that it may be used as a biomarker to evaluate the progression of OA.     

Increased serum brain-derived neurotrophic factor with high-intensity interval training in stroke patients: A randomized controlled trial

BackgroundPhysiological adaptations of stroke patients after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) remain unclear.ObjectiveThis study determined the HIIT and MICT effects on aerobic capacity, cerebral oxygenation, peak cardiac output (CO), and serum brain-derived neurotrophic factor (BDNF) in stroke patients.MethodsWe included 23 stroke patients with age about 55 years and stroke duration > 24 months; participants completed 36 sessions of exercise training for 30 min; 13 were randomly assigned to perform MICT at 60% of peak oxygen consumption (VO_2peak) and 10 to perform HIIT at alternating 80% (3 min) and 40% (3 min) VO_2peak. Before and after interventions, we evaluated VO_2peak, peak CO, arteriovenous oxygen difference (AV O_2diff), bilateral frontal cortex oxygenation (relative changes of oxyhemoglobin Δ[O₂Hb], deoxyhemoglobin Δ[HHb], and total hemoglobin Δ[THb] levels), serum brain-derived neurotrophic factor (BDNF) level, and fluorescent cell staining for neuron morphology and percentage of cell-bearing neurites (% neurites).ResultsHIIT induced significant increases in VO_2peak (P = 0.008), CO (P = 0.038), Δ[HHb] (P = 0.046), Δ[THb] (P = 0.046), and serum BDNF level (P = 0.012). The improvement in VO_2peak was significantly greater with HIIT than MICT (20.7% vs. 9.8%, P = 0.031), as was AV O_2diff (P = 0.041), Δ[HHb] (P = 0.027), and serum BDNF level (P < 0.001). HIIT facilitated neuron dendritic protrusions (greater % neurites, P = 0.012) with prominent redistribution of mitochondria.ConclusionAs compared with MICT, HIIT-improved aerobic capacity by increasing systemic tissue O₂ extraction in stroke patients. Increased cerebral O₂ utilization in the involved hemisphere was also identified after HIIT. These physiological adaptations may be associated with increased serum BDNF level. In vitro dendritic growth in neurons treated with serum from HIIT participants may imply significant effects on neuron activities as compared with MICT.ClinicalTrials.gov identifierNCT04135391.     

Metabolomic analysis of serum by (1) H NMR spectroscopy in amyotrophic lateral sclerosis

BackgroundAmyotrophic lateral sclerosis (ALS), an invariably fatal neurological disorder shows complicated pathogenesis that poses challenges with respect to diagnosis as well as monitoring of disease progression.MethodsWe investigated metabolite profiles in the serum of 30 patients with ALS, 10 patients of Hirayama disease, which served as a neurological disease control and 25 healthy controls by using (1) H NMR spectroscopy.ResultsCompared to healthy controls, the ALS patients had higher quantities of glutamate (P < 0.001), beta-hydroxybutyrate (P < 0.001), acetate (P < 0.01), acetone (P < 0.05), and formate (P < 0.001), and lower concentrations of glutamine (P < 0.02), histidine (P < 0.001) and N-acetyl derivatives. On the other hand, Hirayama disease patients had significantly higher median concentrations of pyruvate (P < 0.05), glutamate (P < 0.001), formate (P < 0.05) and lower median concentrations of N-acetyl derivatives. Furthermore, we also found that serum glutamate showed a positive correlation (P < 0.001, r = 0.6487) whereas, histidine showed a negative correlation (P < 0.001, r = ? 0.5641) with the duration of the disease in ALS.ConclusionsSuch (1) H NMR study of serum may reveal abnormal metabolite patterns, which could have the potential to serve as surrogate markers for monitoring ALS disease progression.     

Serum caspase 3 levels are associated with early mortality in severe septic patients

ObjectiveHigher caspase 3 activity has been found in lymphocytes of septic patients than of healthy controls. However, an association between serum caspase 3 levels at moment of severe sepsis diagnosis and mortality in septic patients has not been previously demonstrated, and this was the main objective of the present study.MethodsThis is an observational study of 216 patients with severe sepsis in 6 Spanish intensive care units. We collected serum samples at moment of severe sepsis diagnosis to determine levels of caspase 3 and caspase-cleaved cytokeratin (CCCK) 18. End point was 30-day mortality.ResultsWe found higher serum caspase 3 levels (P < .001) and caspase-cleaved cytokeratin 18 (P = .001) in nonsurvivors (n = 76) than in survivors (n = 140). Multiple binary logistic regression analysis showed that serum caspase 3 levels greater than 0.25 ng/mL were associated with 30-day mortality (odds ratio, 6.51; 95% confidence interval, 3.32-12.77; P < .001). Receiver operating characteristic analysis showed that the area under the curve to predict 30-day mortality for serum caspase 3 levels was 0.73 (95% confidence interval, 0.67-0.79; P < .001).ConclusionsThe major novel findings of our study were that there is an association between serum caspase 3 levels at moment of severe sepsis diagnosis and mortality in septic patients and that serum caspase 3 levels could be used as prognostic biomarker, and further studies are needed to corroborate these findings.     

Evaluation of apolipoprotein M as a biomarker of coronary artery disease

ObjectiveTo investigate the possible role of apolipoprotein M (ApoM) in the development of coronary artery disease (CAD).Design and methodsCase-controlled study, which consisted of 118 CAD patients and 255 unrelated subjects used as control group. Plasma concentration of ApoM was determined by dot blot, severity of CAD was expressed with Gensini score or the numbers of lesioned coronary arteries, and serum lipid levels were also measured.Results and discussionOur study shows the mean level of plasma ApoM is 1.3757 ± 0.1493 ODu mm^? 2 in CAD patients, while it is 1.3502 ± 0.1288 ODu mm^? 2 in control group, and there are significant differences in plasma level of ApoM between two groups (t = 0.032, P < 0.05). Concentration of plasma ApoM is positively associated with plasma total cholesterol (r = 0.38, P = 0.025), high density lipoprotein cholesterol (r = 0.29, P = 0.03), low density lipoprotein cholesterol (r = 0.16, P = 0.03) and apolipoproein A–I (r = 0.24, P = 0.03). Multiple logistic and linear regression analysis showed that plasma concentration of ApoM did not correlate either with the number of lesioned coronaries or the Gensini score after adjusted for conventional cardiovascular risk factors (P > 0.05, respectively).ConclusionThe findings suggest that ApoM could not be an independent risk factor but a biomarker of CAD.     

Epidermal growth factor-like domain 7 promotes cell invasion and angiogenesis in pancreatic carcinoma

Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, was firstly identified as a modulator of smooth muscle cell migration. Though the expression of EGFL7 was reported to be up-regulated during tumorigenesis, the clinical and biological functions of EGFL7 in pancreatic carcinoma (PC) were still not fully elucidated. In this study, we found that the serum EGFL7 level in PC tissues was statistically higher than that in normal subjects (p < 0.001), and its level in non-resectable patients was also higher than that in resectable ones (p = 0.013). Among these resectable PC patients, the postoperative EGFL7 expression was significantly down-regulated when tumors were resected (p = 0.018). Using the immunohistochemistry method, our results demonstrated that the positive expression of EGFL7 was significantly associated with the TNM stage (p = 0.024), lymph node metastasis (p = 0.003) and local invasion (p = 0.022), and the EGFL7 expression closely correlated to the micro-vessel density (MVD) in PC tissues by Spearman analysis (r = 0.941, p = 0.000). In vitro, EGFL7 was silenced by the small interference RNA in PC cells, and our data indicated that down-regulation of EGFL7 did not influence the cycle progression, proliferation, colony formation and apoptosis of PC cells (p > 0.05), whereas inhibition of EGFL7 expression could decrease PaCa-2 cell invasion (p < 0.05). More interestingly, by tubular formation, Chick embryo chorioallantoic membrane (CAM) and ELISA assays, our results revealed that silencing EGFL7 expression represented a strong inhibiting effect on tubular formation of micro-vessels through down-regulating the protein levels of VEGF and Ang-2 (p < 0.05). Our results raised the possibility of using EGFL7 as a potential prognostic biomarker and therapy target of PC, and down-regulation of EGFL7 might be considered to be a potentially important molecular treatment strategy for patients with PC.