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Prognostic significance of tissue factor in patients with pancreatic cancer: a systematic review protocol.

ABSTRACT: INTRODUCTION:Pancreatic cancer is a highly aggressive digestive system tumour with poor prognosis. Venous thromboembolism (VTE) is a well-known complication of pancreatic cancer, and tissue factor (TF) contributes to the generation of a hypercoagulable state and thrombotic disease in pancreatic cancer. Several studies showed that an elevated TF level was related to the development of VTE and influenced the survival of patients with pancreatic cancer. Thus, we wish to conduct a systematic review of literature to clarify the prognostic significance of TF in pancreatic cancer. METHODS AND ANALYSIS:Studies comparing the circulating microparticle-associated TF (MP TF) level between patients who had pancreatic cancer with and without VTE will be included to evaluate the roles of TF in VTE development. Studies comparing the survival data between patients with high TF expression and low TF expression will also be included to explore the association of TF expression with patient survival. The outcomes are plasma MP TF level and survival endpoints (overall and progression-free survival), respectively. Primary studies of any type published in English will be included. Two reviewers will search Medline, EMBASE and Cochrane databases from inception to June 2020, retrieve relevant studies, and independently select the literatures and extract data from the included studies. The quality of each included study will be assessed by the Newcastle-Ottawa Scale score. The HR and 95%?CI of each study will be pooled for survival outcome, and the standardised mean difference (SMD) with 95% CIs will be used for continuous outcomes. If meta-analysis is inappropriate, the result will only be reported qualitatively. Subgroup and sensitivity analyses will be considered to identify sources of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method will be applied to assess the level of evidence of this systematic review. ETHICS AND DISSEMINATION:There are no concerning ethical issues. The results will be published. PROSPERO REGISTRATION NUMBER:CRD42019133665.

SUBMITTER: Li H

PROVIDER: S-EPMC7490930 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Prognostic significance of tissue factor in patients with pancreatic cancer: a systematic review protocol.

Li Haiyuan H Yu Yang Y Shi Qianling Q Chen Xueping X Zheng Peng P Wang Dengfeng D Tao Pengxian P Gu Baohong B Li Xuemei X Zhang Tao T Xiang Lin L Xi Dayong D Gao Lei L Maswikiti Ewetse Paul P Chen Hao H

BMJ open 20200914 9

<h4>Introduction</h4>Pancreatic cancer is a highly aggressive digestive system tumour with poor prognosis. Venous thromboembolism (VTE) is a well-known complication of pancreatic cancer, and tissue factor (TF) contributes to the generation of a hypercoagulable state and thrombotic disease in pancreatic cancer. Several studies showed that an elevated TF level was related to the development of VTE and influenced the survival of patients with pancreatic cancer. Thus, we wish to conduct a systematic ...[more]

PMID: 32928856

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Project description:Background:Galectins constitute a family of ?-galactoside-binding proteins, which influence various hallmarks of pancreatic cancer, including cell proliferation, invasion and migration; immune escape; and angiogenesis. Although many studies have concentrated on the role of galectins in pancreatic cancer, the results remain controversial. Hence, we performed a comprehensive meta-analysis to clarify the precise diagnostic and prognostic value of galectins in pancreatic cancer. Methods:PubMed/MEDLINE, EMBASE and Web of Science were used to search related published literature up to July 2019. Pooled hazard ratios (HRs), diagnostic accuracy variables and related 95% confidence intervals (CIs) were calculated using STATA 14.0 software. Results:Eleven studies including 1227 participants met our inclusion criteria. High expression of galectin family was not correlated with overall survival (OS) in pancreatic cancer (HR, 1.19; 95% CI 0.67-2.11). According to subgroup analysis, high levels of galectin-1 were significantly correlated with worse OS in pancreatic cancer (HR, 4.77; 95% CI 2.47-9.21), while high levels of tandem-repeat galectins (galectin-4 or galectin-9) predicted both better OS (HR, 0.63; 95% CI 0.46-0.86) and disease-free survival (DFS) (HR, 0.63; 95% CI 0.48-0.83). The expression levels of galectin-3 did not directly correlate with prognosis (HR, 0.99; 95% CI 0.40-2.46). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratios of galectin-3 were 0.64 (95% CI 0.41-0.82), 0.76 (95% CI 0.59-0.88), 2.70 (95% CI 1.21-6.1), and 0.47 (95% CI 0.23-0.98), respectively. The area under the curve (AUC) of galectin-3 was 0.77. Conclusion:Taken together, our results suggest that high expression of galectin-1 and low levels of galectin-4 or galectin-9 are predictors of worse prognosis in pancreatic cancer patients. The expression of galectin-3 was not directly related to OS and other clinical characteristics. Although galectin-3 exhibited some diagnostic value in patients with pancreatic cancer in this meta-analysis, clinical application prospects remain to be validated. Further studies are warranted to confirm and strengthen these findings.

Project description:Pancreatic cancer (PC) is a highly aggressive malignant tumor with a high mortality rate. It is urgent to find optimal molecular targets for the early diagnosis and treatment of PC. Here, we aimed to systematically analyze the prognostic, diagnostic, and clinicopathological significance of circular RNAs (circRNAs) in PC. Relevant studies were screened through PubMed, Web of Science, and other databases. The prognostic value of PC-associated circRNAs was assessed using the composite hazard ratio (HR), the diagnostic performance was assessed using the area under the summary receiver operator characteristic (SROC) curve (AUC), and the correlation with clinicopathological characteristics using the composite odds ratio (OR) was explored. In our study, 48 studies were included: 34 for prognosis, 11 for diagnosis, and 30 for correlation with clinicopathological characteristics. For prognosis, upregulated circRNAs were associated with poorer overall survival (OS) (HR = 2.02) and disease-free survival/progression-free survival (HR = 1.84) while downregulated circRNAs were associated with longer OS (HR = 0.55). Notably, the combination of circRNAs, including hsa_circ_0064288, hsa_circ_0000234, hsa_circ_0004680, hsa_circ_0071036, hsa_circ_0000677, and hsa_circ_0001460, was associated with worse OS (HR = 2.35). For diagnosis, the AUC was 0.83, and the pooled sensitivity and specificity were 0.79 and 0.73, respectively. For clinicopathologic characteristics, upregulated circRNAs were associated with poorer tumor differentiation, more nerve and vascular invasion, higher T stage, lymphatic metastasis, distant metastasis, advanced TNM stage, and higher preoperative CA19-9 level. In contrast, downregulated circRNAs were negatively associated with PC differentiation and lymphatic metastasis. Overall, our results showed that circRNAs are closely related to the prognosis and clinicopathological characteristics of PC patients and could be utilized for early diagnosis; thus, they are promising biomarkers for clinical application in PC.

Project description:INTRODUCTION:Idiopathic pulmonary fibrosis(IPF) is chronic fibrosing interstitial pneumonia of unknown aetiology. IPF is diagnosed based on the exclusion of known causes such as connective tissue diseases(CTDs). However, some patients fail to meet defined CTD criteria regardless of an implication of immunological involvement and these cases were described in a variety of terms. The classification criteria of this clinical entity consist of a combination of clinical, serological and morphological findings and it is reported to be distinct from IPF. However, the significance of the sole presence of autoantibodies complicated with IPF is still unknown. Therefore, this systematic review aims to clarify the significance of autoantibodies complicated with IPF. METHODS AND ANALYSIS:IPF with any autoantibody associated with CTDs is eligible for the review. Primary outcomes are all-cause mortality and pulmonary-cause mortality, while secondary outcomes include a progression of the disease, a deterioration of health-related quality of life and the development of a defined CTD. Primary studies of any type except a case report are included. Two reviewers search four electronic databases such as Medline, EMBASE, Science Citation Index Expanded and Google Scholar from each inception through 1 February 2018 and extract data independently. A risk of bias in individual studies is assessed by the Quality in Prognostic Studies tool. Meta-analysis is sought to be conducted if three or more studies report an outcome for a specific autoantibody with the same statistics. If it is inappropriate to combine data due to substantial heterogeneity, the result is reported qualitatively. Subgroup and sensitivity analyses are considered to identify the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method is applied to evaluate the evidence level of the result. ETHICS AND DISSEMINATION:There is no concerning ethical issue. The result will be sought for publication. PROSPERO REGISTRATION NUMBER:CRD42017077336.

Project description:ObjectivesMAP4K5 plays an important role in regulating a range of cellular responses and is involved in Wnt signaling in hematopoietic cells. However, its functions in human malignancies have not been studied. The major objectives of this study are to examine the expression, functions and clinical significance of MAP4K5 in pancreatic ductal adenocarcinoma (PDAC).Materials and methodsThe expression levels of MAP4K5, E-cadherin, vimentin, and carboxylesterase 2 (CES2) were examined by immunohistochemistry in 105 PDAC and matched non-neoplastic pancreas samples from our institution. The RNA sequencing data of 112 PDAC patients were downloaded from the TCGA data portal. Immunoblotting and RNA sequencing analysis were used to examine the expression of MAP4K5 and E-cadherin in pancreatic cancer cell lines. The effect of knockdown MAP4K5 using siRNA on the expression of CDH1 and vimentin were examined by Real-time RT-PCR in Panc-1 and AsPC-1 cells. Statistical analyses were performed using IBM SPSS Statistics.ResultsMAP4K5 protein is expressed at high levels specifically in the pancreatic ductal cells of 100% non-neoplastic pancreas samples, but is decreased or lost in 77.1% (81/105) of PDAC samples. MAP4K5-low correlated with the loss of E-cadherin (P = 0.001) and reduced CES2 expression (P = 0.002) in our patient populations. The expression levels of MAP4K5 mRNA directly correlated with the expression levels of CDH1 mRNA (R = 0.2490, P = 0.008) in the second cohort of 112 PDAC patients from The Cancer Genome Atlas (TCGA) RNA-seq dataset. Similar correlations between the expression of MAP4K5 and E-cadherin were observed both at protein and mRNA levels in multiple pancreatic cancer cell lines. Knockdown MAP4K5 led to decreased CDH1 mRNA expression in Panc-1 and AsPC-1 cells. MAP4K5-low correlated significantly with reduced overall survival and was an independent prognosticator in patients with stage II PDAC.ConclusionsMAP4K5 expression is decreased or lost in majority of PDACs. The strong associations between low MAP4K5 expression and loss of E-cadherin, reduced CES2 expression and decreased overall survival may suggest an important role of MAP4K5 in epithelial-to-mesenchymal transition, chemotherapy resistance and tumor progression in pancreatic cancer. Targeting impaired MAP4K5 signaling may represent a new therapeutic strategy for pancreatic cancer.

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Prognostic significance of tissue factor in patients with pancreatic cancer: a systematic review protocol.

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Prognostic significance of tissue factor in patients with pancreatic cancer: a systematic review protocol.

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