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ALPPL2 Is a Potential Diagnostic Biomarker for Pancreatic Cancer-Derived Extracellular Vesicles.

ABSTRACT: Pancreatic cancer is an aggressive malignancy that often goes undiagnosed in the early stages. Non-invasive, early, and accurate diagnosis is therefore undoubtedly the "holy grail" of pancreatic cancer research. However, despite extensive research efforts, there is no definitive biomarker for this cancer. Previously, we identified alkaline phosphatase placental-like 2 (ALPPL2) as a diagnostic biomarker for pancreatic ductal adenocarcinoma and developed a 2'-fluoro modified RNA aptamer toward it. In this study, we show that ALPPL2 is present in pancreatic cancer extracellular vesicles (EVs) and therefore has potential application in liquid biopsy-based diagnostic strategies. We also developed ALPPL2 direct and sandwich aptamer-linked immobilized sorbent assay (ALISA) for EVs, which could sensitively and specifically detect the protein. We believe that our ALISA format may have a potential diagnostic utility in screening pancreatic-cancer-derived EVs.

SUBMITTER: Shin HS

PROVIDER: S-EPMC6819892 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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ALPPL2 Is a Potential Diagnostic Biomarker for Pancreatic Cancer-Derived Extracellular Vesicles.

Shin Hye-Su HS Jung Sang Baek SB Park Sungho S Dua Pooja P Lee Dong Ki DK

Molecular therapy. Methods & clinical development 20190912

Pancreatic cancer is an aggressive malignancy that often goes undiagnosed in the early stages. Non-invasive, early, and accurate diagnosis is therefore undoubtedly the "holy grail" of pancreatic cancer research. However, despite extensive research efforts, there is no definitive biomarker for this cancer. Previously, we identified alkaline phosphatase placental-like 2 (ALPPL2) as a diagnostic biomarker for pancreatic ductal adenocarcinoma and developed a 2'-fluoro modified RNA aptamer toward it. ...[more]

PMID: 31687420

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Project description:Gliomas are the most common type of the malignant brain tumor, which arise from glial cells. They make up about 40% of all primary brain tumors and around 70% of all primary malignant brain tumors. They can occur anywhere in the central nervous system (CNS) and have a poor prognosis. The average survival of glioma patients is approximately 6-15 months with poor aspects of life. In this edge, identification of proteins secreted by cancer cells is of special interest because it may provide a better understanding of tumor progression and provide early diagnosis of the diseases. Extracellular vesicles (EVs) were isolated from pooled plasma of healthy controls (n=03) and patients with different grades of glioma (Grade I or II or III, n=03 each). Nanoparticle tracking analysis, western blot, and flow cytometry were performed to determine the size, morphology, the concentration of glioma-derived vesicles and EV marker, CD63. Further, iTRAQ-based LC-MS/MS analysis of EV protein was performed to determine the differential protein abundance in extracellular vesicles across different glioma grades. We further verified galectin-3 binding protein (LGALS3BP) by ELISA in individual blood plasma and plasma-derived vesicles from control and glioma patients (n=40 each). Analysis by Max Quant identified 123 proteins from the pooled patient exosomes, out of which 34, 21, and 14 proteins were found to be differentially abundant by more than 1.3-fold in the different grades of glioma grade I, pilocytic astrocytoma; grade II, diffuse astrocytoma; grade III, anaplastic astrocytoma, respectively, in comparison with the control samples. A total of seven proteins-namely, CRP, SAA2, SERPINA3, SAA1, C4A, LV211, and KV112-showed differential abundance in all the three grades. LGALS3BP was seen to be upregulated across the different grades, and ELISA analysis from individual blood plasma and plasma-derived extracellular vesicles confirmed the increased expression of LGALS3BP in glioma patients (p<0.001). The present study provides LGALS3BP as a potential biomarker for early detection of glioma and improve survival outcome of the patient. The present study further provides the information of progression and monitoring the tumor grades (grade 1, grade II, grade III).

Dataset Information

ALPPL2 Is a Potential Diagnostic Biomarker for Pancreatic Cancer-Derived Extracellular Vesicles.

Publications

ALPPL2 Is a Potential Diagnostic Biomarker for Pancreatic Cancer-Derived Extracellular Vesicles.

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