Prognostic value of glypican-1 for patients with advanced pancreatic cancer following regional intra-arterial chemotherapy.

Regional intra-arterial chemotherapy (RIAC) is a potential alternative treatment for advanced pancreatic cancer (APC) with fewer adverse effects than other treatment options. However, specific biomarkers to determine the prognosis of patients with APC have thus far, been unsatisfactory. Glypican-1 (GPC1) in exosomes has been identified as an early diagnostic biomarker for pancreatic adenocarcinoma. The aim of the present study was to investigate whether the presence of GPC1 in extracellular vesicles (EVs) could serve as a predictor of RIAC outcome for patients with APC. EVs in circulation were isolated and the percentage of GPC1+ EVs was measured using flow cytometry. Compared with healthy individuals, the levels of GPC1+ EVs were significantly increased in patients with APC (P<0.01). Following RIAC treatment, the percentage of GPC1+ EVs was decreased (P=0.023). Furthermore, patients with APC exhibiting a greater decrease of GPC1+ EVs experienced improved overall survival (OS) rates. In summary, the present study provides insights into identifying GPC1 as a novel prognostic biomarker for patients with APC following RIAC treatment.

[1]  Honghe Zhang,et al.  Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: a meta-analysis. , 2015, International journal of clinical and experimental medicine.

[2]  David Elashoff,et al.  Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. , 2010, Gastroenterology.

[3]  T. Conroy,et al.  Current standards and new innovative approaches for treatment of pancreatic cancer. , 2016, European journal of cancer.

[4]  Paul Harrison,et al.  Classification, Functions, and Clinical Relevance of Extracellular Vesicles , 2012, Pharmacological Reviews.

[5]  Troels Z. Kristiansen,et al.  Biomarker Discovery from Pancreatic Cancer Secretome Using a Differential Proteomic Approach*S , 2006, Molecular & Cellular Proteomics.

[6]  H. Cárdenes,et al.  Locally advanced pancreatic cancer: current therapeutic approach. , 2006, The oncologist.

[7]  He Ren,et al.  Regional Intra-Arterial vs. Systemic Chemotherapy for Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials , 2012, PloS one.

[8]  C. Théry,et al.  Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. , 2014, Annual review of cell and developmental biology.

[9]  Raghu Kalluri,et al.  The biology and function of exosomes in cancer. , 2016, The Journal of clinical investigation.

[10]  W. George,et al.  Regional chemotherapy for inoperable pancreatic carcinoma , 1996, Cancer.

[11]  L. Wood,et al.  Pancreatic cancer , 2016, The Lancet.

[12]  T. Yasuda,et al.  A new method of intra-arterial regional chemotherapy with more selective drug delivery for locally advanced pancreatic cancer. , 1996, Hepato-gastroenterology.

[13]  Christian Pilarsky,et al.  Glypican-1 identifies cancer exosomes and detects early pancreatic cancer , 2015, Nature.

[14]  Zhen Zhang,et al.  Intensity modulated radiotherapy for locally advanced and metastatic pancreatic cancer: a mono-institutional retrospective analysis , 2015, Radiation Oncology.

[15]  J. Prados,et al.  Serum Cytokine Profile in Patients With Pancreatic Cancer , 2014, Pancreas.

[16]  Simon C Watkins,et al.  Isolation of biologically-active exosomes from human plasma. , 2014, Journal of immunological methods.

[17]  H. Friess,et al.  Correlation of glypican-1 expression with TGF-beta, BMP, and activin receptors in pancreatic ductal adenocarcinoma. , 2006, International journal of oncology.

[18]  M. Hidalgo,et al.  Pancreatic ductal adenocarcinoma: metastatic disease , 2017, Clinical and Translational Oncology.

[19]  W. Fisher,et al.  Pancreatic cancer: advances in treatment. , 2014, World journal of gastroenterology.

[20]  S. Steinberg,et al.  Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial , 2011, Trials.

[21]  Michael Liem,et al.  Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma , 2013, Proteomics.

[22]  D. Klimstra,et al.  Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. , 1996, Annals of surgery.

[23]  T. Sasada,et al.  Intra-arterial Infusion Chemotherapy With 5-Fluorouracil and Cisplatin in Advanced Pancreatic Cancer: A Feasibility Study , 2008, American journal of clinical oncology.

[24]  D. V. Von Hoff,et al.  Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  M. McCarter,et al.  Characteristics of 10-Year Survivors of Pancreatic Ductal Adenocarcinoma. , 2015, JAMA surgery.

[26]  Xiaoyu Liu,et al.  Gemcitabine-Based Regional Intra-Arterial Infusion Chemotherapy in Patients With Advanced Pancreatic Adenocarcinoma , 2016, Medicine.

[27]  H. Friess,et al.  The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer. , 1998, The Journal of clinical investigation.

[28]  Y. Yamashita,et al.  5-Fluorouracil Intra-arterial Infusion Combined With Systemic Gemcitabine for Unresectable Pancreatic Cancer , 2005, Pancreas.

[29]  A. Bozdağ,et al.  The diagnostic importance of CEA and CA 19-9 for the early diagnosis of pancreatic carcinoma. , 2000, Hepato-gastroenterology.

[30]  J. Long,et al.  Combinational therapy: new hope for pancreatic cancer? , 2012, Cancer letters.

[31]  S. Mulvihill,et al.  Biomarkers in pancreatic adenocarcinoma: current perspectives , 2016, OncoTargets and therapy.

[32]  Xing-ming Jiang,et al.  GPC1 Regulated by miR-96-5p, Rather than miR-182-5p, in Inhibition of Pancreatic Carcinoma Cell Proliferation , 2014, International journal of molecular sciences.

[33]  Feng Yang,et al.  Effect of multiple‐phase regional intra‐arterial infusion chemotherapy on patients with resectable pancreatic head adenocarcinoma , 2009, Chinese medical journal.

[34]  Graça Raposo,et al.  Extracellular vesicles: Exosomes, microvesicles, and friends , 2013, The Journal of cell biology.

[35]  C. Corke,et al.  A Seldinger Technique for Minitracheostomy Insertion , 1988, Anaesthesia and intensive care.

[36]  Douglas B. Evans,et al.  Tumor‐Node‐Metastasis Staging of Pancreatic Adenocarcinoma , 2008, CA: a cancer journal for clinicians.

[37]  Lian Duan,et al.  GPC-1 may serve as a predictor of perineural invasion and a prognosticator of survival in pancreatic cancer. , 2017, Asian journal of surgery.

[38]  M. Schlumpberger,et al.  Characterization of RNA from Exosomes and Other Extracellular Vesicles Isolated by a Novel Spin Column-Based Method , 2015, PloS one.

[39]  A. Shiras,et al.  Tumor exosomes: cellular postmen of cancer diagnosis and personalized therapy. , 2016, Nanomedicine.