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Background: Transforming growth factor-beta (TGF-β) is associated with a higher incidence of distant metastasis and decreased survival. Whether TGF-β can be used as a prognostic indicator of colorectal cancer (CRC) remains controversial., Methods: The Medline, EMBASE and Cochrane databases were searched from their inception to March 2016. The studies that focused on TGF-β as a prognostic factor in patients with CRC were included in this analysis. Overall survival (OS) and disease-free survival (DFS) were analysed separately. A meta-analysis was performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated., Results: Twelve studies were included in the analysis, of which 8 were used for OS and 7 for DFS. In all, 1622 patients with CRC undergoing surgery were included. Combined HRs suggested that high expression of TGF-β had a favourable impact on OS (HR = 1.68, 95% CI: 1.10-2.59) and DFS (HR = 1.11, 95% CI: 1.03-1.19) in CRC patients. For OS, the combined HRs of Asian studies and Western studies were 1.50 (95% CI: 0.61-3.68) and 1.80 (95% CI: 1.33-2.45), respectively. For DFS, the combined HRs of Asian studies and Western studies were 1.42 (95% CI: 0.61-3.31) and 1.11 (95% CI: 1.03-1.20), respectively., Conclusions: This meta-analysis demonstrates that TGF-β can be used as a prognostic biomarker for CRC patients undergoing surgery, especially for CRC patients from Western countries.

Abstract Background Dipeptidyl peptidase-4 (DPP4) regulates blood glucose levels and inflammation, and it is also implicated in the pathophysiological process of myocardial infarction (MI). Plasma DPP4 activity (DPP4a) may provide prognostic information regarding outcomes for ST-segment elevation MI (STEMI) patients. Methods Blood samples were obtained from 625 consecutively admitted, percutaneous coronary intervention-treated STEMI patients with a mean age of 57 years old. DPP4a was quantified using enzymatic assays. Results The median follow-up period was 30 months. Multivariate Cox-regression analyses (adjusted for confounding variables) showed that a 1 U/L increase of DPP4a did not associate with risks of major adverse cardiac or cerebrovascular events (MACCE), cardiovascular mortality, MI, heart failure readmission, stroke, non-cardiovascular mortality and repeated revascularization. However, in a subset of 149 diabetic STEMI patients, DPP4a associated with an increased risk of MACCE (HR 1.16; 95% CI 1.04–1.30; p = 0.01). Conclusions DPP4a did not associate with cardiovascular events and non-cardiovascular mortality in non-diabetic STEMI patients. However, DPP4a may be associated with future MACCE in diabetic STEMI patients. Trial registration NCT03046576, registered on 5 February, 2017, retrospectively registered

Abstract Background Transforming growth factor-beta (TGF-β) is associated with a higher incidence of distant metastasis and decreased survival. Whether TGF-β can be used as a prognostic indicator of colorectal cancer (CRC) remains controversial. Methods The Medline, EMBASE and Cochrane databases were searched from their inception to March 2016. The studies that focused on TGF-β as a prognostic factor in patients with CRC were included in this analysis. Overall survival (OS) and disease-free survival (DFS) were analysed separately. A meta-analysis was performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Results Twelve studies were included in the analysis, of which 8 were used for OS and 7 for DFS. In all, 1622 patients with CRC undergoing surgery were included. Combined HRs suggested that high expression of TGF-β had a favourable impact on OS (HR = 1.68, 95% CI: 1.10–2.59) and DFS (HR = 1.11, 95% CI: 1.03–1.19) in CRC patients. For OS, the combined HRs of Asian studies and Western studies were 1.50 (95% CI: 0.61–3.68) and 1.80 (95% CI: 1.33–2.45), respectively. For DFS, the combined HRs of Asian studies and Western studies were 1.42 (95% CI: 0.61–3.31) and 1.11 (95% CI: 1.03–1.20), respectively. Conclusions This meta-analysis demonstrates that TGF-β can be used as a prognostic biomarker for CRC patients undergoing surgery, especially for CRC patients from Western countries.

Background: There is debate as to whether c-Myc predicts prognosis in colorectal cancer (CRC). In this study, we aimed to review the association between c-Myc and CRC prognosis.Methods: Pertinent studies were identified by searching electronic databases and carefully reviewing the reference lists of pertinent studies until March 2016. The summary hazard ratio (HR) and corresponding 95% confidence interval (CI) were calculated to study the association between c-Myc and CRC prognosis.Results: Eight cohort studies (including seven studies about overall survival [OS] and one study about disease free survival [DFS]) were included. The pooled HR of OS was 1.13 (95% CI: 0.66–1.95). In subgroup analysis, no significant association between c-Myc and CRC prognosis was found in the studies either from Western countries (HR: 0.87, 95% CI: 0.68–1.10) or Asian countries (HR: 1.89, 95% CI: 0.62–5.77). HRs were 0.86 (95% CI: 0.38–1.94) and 1.57 (95% CI: 0.73–3.39) for the studies using univariate analysis and multivariate analysis, respectively. HR from the studies that examined DNA level was significantly different (HR: 2.05, 95% CI: 1.22–3.46); while that about RNA level or protein level was not significantly different.Conclusion: c-Myc was not associated with CRC prognosis in this meta-analysis. However, the conclusion is preliminary and should be examined in future studies.

Sarcopenia is an important factor affecting the prognostic outcomes in adult cancer patients. Gastric cancer is considered an age-related disease and is one of the leading causes of global cancer mortality. We aimed to establish an effective age-related model at a molecular level to predict the prognosis of patients with gastric cancer. TCGA STAD (stomach adenocarcinoma) and NCBI GEO database were utilized in this study to explore the expression, clinical relevance and prognostic value of age-related mRNAs in stomach adenocarcinoma through an integrated bioinformatics analysis. WGCNA co-expression network, Univariate Cox regression analysis, LASSO regression and Multivariate Cox regression analysis were implemented to construct an age-related prognostic signature. As a result, sarcopenia is not only an unfavorable factor for OS (overall survival) in patients with tumor of gastric (HR: 1.707, 95%CI: 1.437–2.026), but also increases the risk of postoperative complications in patients with gastric cancer (OR: 2.904, 95%CI: 2.150–3.922). A panel of 5 mRNAs (DCBLD1, DLC1, IGFBP1, RNASE1 and SPC24) were identified to dichotomize patients with significantly different OS and independently predicted the OS in TCGA STAD (HR = 3.044, 95%CI = 2.078–4.460, P < 0.001). The study provided novel insights to understand STAD at a molecular level and indicated that the 5 mRNAs might act as independent promising prognosis biomarkers for STAD. Sarcopenia and the 5-mRNA risk module as a combined factor to predict prognosis may play an important role in clinical diagnosis. • The strong association between sarcopenia and short- and long-term clinical outcomes of STAD patients • Age play important roles in sarcopenia and gastric cancer. • WGCNA analysis was used to screen age-related mRNAs. • Sarcopenia and the 5-mRNA module as a combined factor to predict prognosis might play an important role in STAD. [ABSTRACT FROM AUTHOR]

Background: The long-term outcomes for patients after coronary artery bypass grafting (CABG) have been received more and more concern. The existing prediction models are mostly focused on in-hospital operative mortality after CABG, but there is still little research on long-term mortality prediction model for patients after CABG.Objective: To develop and validate a novel nomogram for predicting 3-year mortality in critically ill patients after CABG.Methods: Data for developing novel predictive model were extracted from Medical Information Mart for Intensive cart III (MIMIC-III), of which 2929 critically ill patients who underwent CABG at the first admission were enrolled.Results: A novel prognostic nomogram for 3-year mortality was constructed with the seven independent prognostic factors, including age, congestive heart failure, white blood cell, creatinine, SpO2, anion gap, and continuous renal replacement treatment derived from the multivariable logistic regression. The nomogram indicated accurate discrimination in primary (AUC: 0.81) and validation cohort (AUC: 0.802), which were better than traditional severity scores. And good consistency between the predictive and observed outcome was showed by the calibration curve for 3-year mortality. The decision curve analysis also showed higher clinical net benefit than traditional severity scores.Conclusion: The novel nomogram had well performance to predict 3-year mortality in critically ill patients after CABG. The prediction model provided valuable information for treatment strategy and postdischarge management, which may be helpful in improving the long-term prognosis in critically ill patients after CABG. [ABSTRACT FROM AUTHOR]

As a class of endogenous non-coding RNAs with closed-loop structure, circular RNAs (circRNAs) are receiving more and more attention. CircRNAs have been reported to be widely expressed in various human cancers and are implicated in tumorigenesis and progression. The present study aimed to systematically evaluate the clinicopathological, diagnostic and prognostic values of circRNAs in lung cancer. We searched literature from PubMed, Web of science, Cochrane Library, EMBASE and Ovid online databases up to May 29, 2020. Statistical analyses were undertaken based on Stata 11.0, Meta-DiSc 1.4, and RevMan 5.3 software. Finally, a total of 63 eligible articles were included in our meta-analysis, including 18 studies for diagnosis, 22 studies for prognosis and 57 studies for clinicopathological features. In terms of diagnostic values, circRNAs could discriminate between lung cancer patients and the normal individuals with a relatively high pooled area under the curve (AUC) of 0.83 (95%CI, 0.80–0.86). For the prognostic values, we found that elevated expression of oncogenic circRNAs could predict poor survival outcomes based on multivariate analysis (HR = 2.430, 95%CI = 2.003–2.948, P < 0.001 for OS; HR = 2.228, 95%CI = 1.289–3.853, P = 0.004 for DFS) while tumor-suppressor circRNAs was correlated with better OS in univariate analysis (HR = 0.627, 95%CI = 0.519–0.757, P < 0.001). The pooled results suggested that elevated expression of carcinogenic circRNAs was associated with tumor size (OR = 1.676, 95%CI = 1.209–2.323, P = 0.002), smoking statue (OR = 1.260, 95%CI = 1.062–1.494, P = 0.008), TNM stage (OR = 2.345, 95%CI = 1.617–3.399, P < 0.001), differentiation grade (OR = 1.843, 95%CI = 1.228–2.765, P = 0.003), and lymphatic metastasis (OR = 2.097, 95%CI = 1.482–2.967, P < 0.001). Moreover, the expression of tumor-suppressor circRNAs was related to the improved clinicopathological features (lymphatic metastasis: OR = 0.536, 95%CI = 0.311–0.926, P = 0.025). Our meta-analysis demonstrated that circRNAs could be used as feasible and important biomarkers for diagnosis, prognosis and clinicopathological features in lung cancer. [ABSTRACT FROM AUTHOR]

Background: There is debate as to whether c-Myc predicts prognosis in colorectal cancer (CRC). In this study, we aimed to review the association between c-Myc and CRC prognosis. Methods: Pertinent studies were identified by searching electronic databases and carefully reviewing the reference lists of pertinent studies until March 2016. The summary hazard ratio (HR) and corresponding 95% confidence interval (CI) were calculated to study the association between c-Myc and CRC prognosis. Results: Eight cohort studies (including seven studies about overall survival [OS] and one study about disease free survival [DFS]) were included. The pooled HR of OS was 1.13 (95% CI: 0.66–1.95). In subgroup analysis, no significant association between c-Myc and CRC prognosis was found in the studies either from Western countries (HR: 0.87, 95% CI: 0.68–1.10) or Asian countries (HR: 1.89, 95% CI: 0.62–5.77). HRs were 0.86 (95% CI: 0.38–1.94) and 1.57 (95% CI: 0.73–3.39) for the studies using univariate analysis and multivariate analysis, respectively. HR from the studies that examined DNA level was significantly different (HR: 2.05, 95% CI: 1.22–3.46); while that about RNA level or protein level was not significantly different. Conclusion: c-Myc was not associated with CRC prognosis in this meta-analysis. However, the conclusion is preliminary and should be examined in future studies. [ABSTRACT FROM AUTHOR]

Platelet-derived growth factor β (PDGFβ) has been proposed to contribute to the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH), and soluble PDGFRβ (sPDGFRβ) is considered to be an inhibitor of PDGF signaling. We aimed at determining the sPDGFRβ concentrations in the cerebrospinal fluid (CSF) of patients with aneurysmal SAH (aSAH) and analyzing the relationship between sPDGFRβ level and CVS. CSF was sampled from 32 patients who suffered aSAH and five normal controls. Enzyme-linked immunosorbent assay was performed to determine the sPDGFRβ concentrations in the CSF. Functional outcome was assessed using modified Rankin scale (mRS) at 6 months after aSAH. CVS was identified using transcranial Doppler or angio-CT or DSA. The cutoff of sPDGFRβ for CVS was defined on the ROC curve. The concentrations of sPDGFRβ following aSAH were both higher than those of normal controls on days 1-3 and 4-6, and peaked on days 7-9 post-SAH. The cutoff value of sPDGFRβ level on days 1-3 for CVS was defined as 975.38 pg/ml according to the ROC curve (AUC = 0.680, p = 0.082). In addition, CSF sPDGFRβ concentrations correlated with CVS (r = 0.416, p = 0.018), and multivariate analysis indicated that sPDGFRβ level higher than 975.38 pg/ml on days 1-3 was an independent predictor of CVS (p = 0.001, OR = 19.22, 95% CI: 3.27-113.03), but not for unfavorable outcome after aSAH in the current study. CSF sPDGFRβ level increases after aSAH and is higher in patients who developed CVS, and sPDGFRβ level higher than 975.38 pg/ml on days 1-3 is a potential predictor for CVS after SAH. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a highly heterogeneous disease, with biologically and prognostically different subtypes. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. The molecular mechanism underlying AML needs to be further investigated. Here we identify IRF9 as a negative regulator of human AML. We show that IRF9 mRNA and protein levels are down-regulated in human AML samples compared with samples from healthy donors. IRF9 knockdown promotes proliferation, colony formation and survival of OCI/AML-2 and OCI/AML-3 cells, whereas IRF9 overexpression obtains oppose results. Mechanism analysis shows that IRF9 binds SIRT1 promoter and represses SIRT1 expression in OCI/AML-2 and OCI/AML-3 cells. In AML samples, the expression of SIRT1 is up-regulated and negatively correlated with IRF9 level. IRF9 also increases the acetylation of p53, a deacetylation substrate of SIRT1, and promotes the expression of p53 target genes. Knockdown of p53 blocks the effects of IRF9 on cell survival and growth in vitro . These findings provide evidence that IRF9 serves as an important regulator in human AML by repressing SIRT1-p53 pathway and that IRF9 may be a potential target for AML treatment. [ABSTRACT FROM AUTHOR]

Abstract: This study investigated the expression of heat shock protein 90 alpha (Hsp90α) in acute leukemia cells. The expression of Hsp90α was investigated in leukemia cell lines and human bone marrow mononuclear cells derived from acute leukemia patients and from healthy individuals using polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Compared with cells from healthy individuals, the expression of Hsp90α in the untreated patients was higher. Similarly high levels were observed in remission patients. Significantly higher expression levels were observed in all the tested cell lines, and in cells from refractory and relapsed patients. No obvious relationship was observed between the occurrence of graft versus host disease and the expression of Hsp90α. The untreated patients showing higher expression levels of Hsp90α had lower complete remission rates. During remission of untreated patients, the expression of Hsp90α decreased and reached the lowest level after transplantation, but the expression increased again before relapse. Hsp90α was highly expressed in leukemia cells. The expression level of Hsp90α was associated with leukemia prognosis. However, no obvious relationship was observed between the occurrence of graft versus host disease and the expression of Hsp90α. [Copyright &y& Elsevier]

• There is a significant elevation of serum MANF levels after sTBI. • Serum MANF levels are independently correlated with severity of sTBI. • Serum MANF emerges as an independent predictor of long-term poor prognosis after sTBI. • Serum MANF levels may take possession of efficient prognostic predictive capability of sTBI. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is released under endoplasmic reticulum stress, thereby exerting neuroprotective effects. We determined whether serum MANF may be a prognostic biomarker of human severe traumatic brain injury (sTBI). Serum MANF concentrations of 137 sTBI patients and 137 controls were quantified in this prospective cohort study. Patients with extended Glasgow outcome scale (GOSE) scores of 1–4 at post-traumatic 6 months were considered to have poor prognosis. Relationships between serum MANF concentrations and severity plus prognosis were investigated using multivariate analyses. Area under receiver operating characteristic curve (AUC) was calculated for reflecting prognostic efficiency. As compared to controls, there was a significant increase of serum MANF concentrations after sTBI (median, 18.5 ng/ml versus 3.0 ng/ml; P < 0.001), which was independently correlated with Glasgow coma scale (GCS) scores [β, −3.000; 95% confidence interval (CI), −4.525--1.476; VIF, 2.216; P = 0.001], Rotterdam computed tomography (CT) scores (β, 4.020; 95% CI, 1.446–6.593; VIF, 2.234; P = 0.002) and GOSE scores (β, −0.056; 95% CI, −0.089--0.023; VIF, 1.743; P = 0.011). Serum MANF concentrations substantially distinguished risk of poor prognosis with AUC of 0.795 (95% CI, 0.718–0.859) and its concentrations > 23.9 ng/ml was predictive of poor prognosis with 67.7% sensitivity and 81.9% specificity. Serum MANF concentrations combined with GCS scores and Rotterdam CT scores displayed markedly higher prognostic predictive ability than each of them (all P < 0.05). Using restricted cubic spline, there was a linear correlation between serum MANF concentrations and poor prognosis (P = 0.256). Serum MANF concentrations > 23.9 ng/ml was independently associated with poor prognosis (odds ratio, 2.911; 95% CI, 1.057–8.020; P = 0.039). A nomogram was built, where serum MANF concentrations > 23.9 ng/ml, GCS scores and Rotterdam CT scores were integrated. Hosmer and Lemeshow test, calibration curve and decision curve analysis demonstrated such a prediction model was comparatively stable and was of relatively high clinical benefit. Substantially increased serum MANF concentrations after sTBI are highly correlated with traumatic severity and are independently predictive of long-term poor prognosis, suggesting that serum MANF may represent a useful prognostic biochemical marker of human sTBI. [ABSTRACT FROM AUTHOR]