Cystatin F as a key family 2 cystatin subunit and prognostic biomarker for early‑stage pancreatic ductal adenocarcinoma

AbstractEarly-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

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Calcium-activated chloride channel regulator 1 as a prognostic biomarker in pancreatic ductal adenocarcinoma

BMC Cancer ◽

10.1186/s12885-018-5013-2 ◽

2018 ◽

Vol 18 (1) ◽

Cited By ~ 10

Author(s):

Dingyuan Hu ◽

Daniel Ansari ◽

Qimin Zhou ◽

Agata Sasor ◽

Katarzyna Said Hilmersson ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Chloride Channel ◽

Prognostic Biomarker ◽

Ductal Adenocarcinoma

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Reduced expression of desmocollin 2 is an independent prognostic biomarker for shorter patients survival in pancreatic ductal adenocarcinoma

Journal of Clinical Pathology ◽

10.1136/jclinpath-2011-200099 ◽

2011 ◽

Vol 64 (11) ◽

pp. 990-994 ◽

Cited By ~ 31

Author(s):

Z. Hamidov ◽

A. Altendorf-Hofmann ◽

Y. Chen ◽

U. Settmacher ◽

I. Petersen ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Prognostic Biomarker ◽

Ductal Adenocarcinoma

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Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma

Bioscience Reports ◽

10.1042/bsr20200214 ◽

2020 ◽

Vol 40 (7) ◽

Author(s):

Xin Zhao ◽

Di Cao ◽

Zhangyong Ren ◽

Zhe Liu ◽

Shaocheng Lv ◽

...

Keyword(s):

Regression Analysis ◽

Pancreatic Ductal Adenocarcinoma ◽

Promoter Methylation ◽

Methylation Level ◽

Cox Regression ◽

Prognostic Biomarker ◽

Dipeptidyl Peptidase ◽

Ductal Adenocarcinoma ◽

Gene Promoters ◽

Cox Regression Analysis

Abstract Background: Hypermethylation of gene promoters plays an important role in tumorigenesis. The present study aimed to identify and validate promoter methylation-driven genes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC). Methods: Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing polymerase chain reaction (BSP) in paired tumor and normal tissues of 72 PDAC patients. Kaplan−Meier survival analyses were performed to evaluate the clinical value of PMDGs. Results: In GSE49149, the β-value of the dipeptidyl peptidase like 6 (DPP6) promoter was significantly higher in tumor compared with normal samples (0.50 vs. 0.24, P<0.001). In the PDAC cohort of TCGA, the methylation level of the DPP6 promoter was negatively correlated with mRNA expression (r = −0.54, P<0.001). In a multivariate Cox regression analysis, hypermethylation of the DPP6 promoter was an independent risk factor for PDAC (hazard ratio (HR) = 543.91, P=0.002). The results of BSP revealed that the number of methylated CG sites in the DPP6 promoter was greater in tumor samples than in normal samples (7.43 vs. 2.78, P<0.001). The methylation level of the DPP6 promoter was moderately effective at distinguishing tumor from normal samples (area under ROC curve (AUC) = 0.74, P<0.001). Hypermethylation of the DPP6 promoter was associated with poor overall (HR = 3.61, P<0.001) and disease-free (HR = 2.01, P=0.016) survivals for PDAC patients. Conclusion: These results indicate that DPP6 promoter methylation is a potential prognostic biomarker for PDAC.

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In Silico analyses of host immunity and stroma provide prognostic factors in early stage pancreatic ductal adenocarcinoma (PDAC)

Annals of Translational Medicine ◽

10.21037/atm.2020.03.37 ◽

2020 ◽

Vol 8 (6) ◽

pp. 259-259

Author(s):

Madison H. Williams ◽

Daruka Mahadevan

Keyword(s):

Prognostic Factors ◽

Pancreatic Ductal Adenocarcinoma ◽

In Silico ◽

Early Stage ◽

Host Immunity ◽

Ductal Adenocarcinoma ◽

In Silico Analyses

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The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma

Biomedicines ◽

10.3390/biomedicines8120565 ◽

2020 ◽

Vol 8 (12) ◽

pp. 565

Author(s):

Sona Ciernikova ◽

Maria Novisedlakova ◽

Danka Cholujova ◽

Viola Stevurkova ◽

Michal Mego

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Malignant Tumors ◽

Current Knowledge ◽

Early Stage ◽

Poor Response ◽

Response To Therapy ◽

Oral Microbiome ◽

Ductal Adenocarcinoma ◽

The Impact

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors due to the absence of biomarkers for early-stage detection and poor response to therapy. Since mounting evidence supports the role of microbiota composition in tumorigenesis and cancer treatment, the link between microbiome and PDAC has been described. In this review, we summarize the current knowledge regarding the impact of the gut and oral microbiome on the risk of PDAC development. Microenvironment-driven therapy and immune system interactions are also discussed. More importantly, we provide an overview of the clinical trials evaluating the microbiota role in the risk, prognosis, and treatment of patients suffering from PDAC and solid tumors. According to the research findings, immune tolerance might result from the microbiota-derived remodeling of pancreatic tumor microenvironment. Thus, microbiome profiling and targeting represent the potential trend to enhance antitumor immunity and improve the efficacy of PDAC treatment.

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