Combined Expression of Plasma Thrombospondin-2 and CA19-9 for Diagnosis of Pancreatic Cancer and Distal Cholangiocarcinoma: A Proteome Approach

Large, Tessa Y.S. Le; Meijer, Laura L.; Paleckyte, Rosita; Boyd, Lenka N.C.; Kok, Bart; Würdinger, Thomas; Schelfhorst, Tim; Piersma, Sander R.; Pham, Thang V.; Grieken, Nicole C.T. van; Zonderhuis, Barbara M; Daams, Freek; Laarhoven, Hanneke W. M. van; Bijlsma, Maarten F.; Jiménez, Connie R.; Giovannetti, Elisa; Kazemier, Geert

doi:10.1634/theoncologist.2019-0680

Cited by 36 publications

(37 citation statements)

References 43 publications

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“…( 40 )also revealed that THBS2 was significantly increased in pancreatic cancer tissues compared with normal tissues. In addition, both Kim ( 39 ) and Le Large ( 40 ) showed that the combined expression of THBS2 and CA19/9 in plasma can be used as a biomarker for PDAC patients. The above studies have shown that the overexpression of MMP14, ITGA2 and THBS2 promotes pancreatic cancer occurrence and development and indicate that they possess the ability to become therapeutic targets of PDAC.…”

Section: Discussionmentioning

confidence: 90%

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Bioinformatics Analysis of a Prognostic miRNA Signature and Potential Key Genes in Pancreatic Cancer

Chen

Gao

et al. 2021

Front. Oncol.

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BackgroundIn this study, miRNAs and their critical target genes related to the prognosis of pancreatic cancer were screened based on bioinformatics analysis to provide targets for the prognosis and treatment of pancreatic cancer.MethodsR software was used to screen differentially expressed miRNAs (DEMs) and genes (DEGs) downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. A miRNA Cox proportional hazards regression model was constructed based on the miRNAs, and a miRNA prognostic model was generated. The target genes of the prognostic miRNAs were predicted using TargetScan and miRDB and then intersected with the DEGs to obtain common genes. The functions of the common genes were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. A protein-protein interaction (PPI) network of the common genes was constructed with the STRING database and visualized with Cytoscape software. Key genes were also screened with the MCODE and cytoHubba plug-ins of Cytoscape. Finally, a prognostic model formed by the key gene was also established to help evaluate the reliability of this screening process.ResultsA prognostic model containing four downregulated miRNAs (hsa-mir-424, hsa-mir-3613, hsa-mir-4772 and hsa-mir-126) related to the prognosis of pancreatic cancer was constructed. A total of 118 common genes were enriched in two KEGG pathways and 33 GO functional annotations, including extracellular matrix (ECM)-receptor interaction and cell adhesion. Nine key genes related to pancreatic cancer were also obtained: MMP14, ITGA2, THBS2, COL1A1, COL3A1, COL11A1, COL6A3, COL12A1 and COL5A2. The prognostic model formed by nine key genes also possessed good prognostic ability.ConclusionsThe prognostic model consisting of four miRNAs can reliably predict the prognosis of patients with pancreatic cancer. In addition, the screened nine key genes, which can also form a reliable prognostic model, are significantly related to the occurrence and development of pancreatic cancer. Among them, one novel miRNA (hsa-mir-4772) and two novel genes (COL12A1 and COL5A2) associated with pancreatic cancer have great potential to be used as prognostic factors and therapeutic targets for this tumor.

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Section: Discussionmentioning

confidence: 90%

“…Le Large et al ( 40)also revealed that THBS2 was significantly increased in pancreatic cancer tissues compared with normal tissues. In addition, both Kim (39) and Le Large (40) showed that the combined expression of THBS2 and CA19/9 in plasma can be used as a biomarker for PDAC patients.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of a Prognostic miRNA Signature and Potential Key Genes in Pancreatic Cancer

Chen

Gao

et al. 2021

Front. Oncol.

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“…When utilized with CA19-9, it can boost detection of PC in high-risk populations which has been more recently affirmed[ 99 - 101 ]. Le Large et al [ 102 ] reported an AUC of 0.952 for THBS2 and CA19-9 in discriminating patients with cancer compared to healthy donors, however there was no difference in plasma THBS2 expression between patients with PC and distal cholangiocarcinoma highlighting a potential diagnostic dilemma and a lack of specificity associated with the assay[ 102 ].…”

Section: Serological Biomarkers Of Pcmentioning

confidence: 99%

Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket?

O’Neill

Stoita

2021

WJG

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Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis. To combat this, there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma. Currently, serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker. In the search for a biomarker that is both sensitive and specific for the diagnosis of PC, there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC. Currently, promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA (miRNA) in serum and circulating tumour cells. Both these modalities, although in their infancy and yet to be widely accepted into routine clinical practice, possess merit in the early detection of PC. We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC (serum, urinary, salivary, faecal, pancreatic juice and biliary fluid).

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“…These markers are also developing as prognostic/diagnostic factors in clinical study. Large et al demonstrated the co-expression of plasma thrombospondin-2 (THBS2) with CA19-9 in CCA patients [ 76 ]. Furthermore, MMP7, IL-6, S100A6, DKK1 and SSP411 are also abnormally expressed proteins in CCA patients’ serum [ 70 , 77 , 78 , 79 , 80 ].…”

Section: Protein Levels and Post-translational Modifications In CCmentioning

confidence: 99%

Omics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma

et al. 2020

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Cholangiocarcinoma (CCA) has been identified as a highly malignant cancer that can be transformed from epithelial cells of the bile duct, including intrahepatic, perihilar and extrahepatic. High-resolution imaging tools (abdominal ultrasound, computed tomography and percutaneous transhepatic cholangial drainage) are recruited for diagnosis. However, the lack of early diagnostic biomarkers and treatment evaluation can lead to serious outcomes and poor prognosis (i.e., CA19-9, MUC5AC). In recent years, scientists have established a large number of omics profiles to reveal underlying mechanisms and networks (i.e., IL-6/STAT3, NOTCH). With these results, we achieved several genomic alteration events (i.e., TP53mut, KRASmut) and epigenetic modifications (i.e., DNA methylation, histone modification) in CCA cells and clinical patients. Moreover, we reviewed candidate gene (such as NF-kB, YAP1) that drive gene transcription factors and canonical pathways through transcriptomics profiles (including microarrays and next-generation sequencing). In addition, the proteomics database also indicates which molecules and their directly binding status could trigger dysfunction signatures in tumorigenesis (carbohydrate antigen 19-9, mucins). Most importantly, we collected metabolomics datasets and pivotal metabolites. These results reflect the pharmacotherapeutic options and evaluate pharmacokinetic/pharmacodynamics in vitro and in vivo. We reversed the panels and selected many potentially small compounds from the connectivity map and L1000CDS2 system. In this paper, we summarize the prognostic value of each candidate gene and correlate this information with clinical events in CCA. This review can serve as a reference for further research to clearly investigate the complex characteristics of CCA, which may lead to better prognosis, drug repurposing and treatment strategies.

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Combined Expression of Plasma Thrombospondin-2 and CA19-9 for Diagnosis of Pancreatic Cancer and Distal Cholangiocarcinoma: A Proteome Approach

Cited by 36 publications

References 43 publications

Bioinformatics Analysis of a Prognostic miRNA Signature and Potential Key Genes in Pancreatic Cancer

Bioinformatics Analysis of a Prognostic miRNA Signature and Potential Key Genes in Pancreatic Cancer

Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket?

Omics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma

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