Skip to main content
Erschienen in: Pathology & Oncology Research 4/2015

01.09.2015 | Research

Overexpressions of DLL4 and CD105 are Associated with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma

verfasst von: Liangjing Zhou, Leilai Yu, Guoping Ding, Wenchao Chen, Sixin Zheng, Liping Cao

Erschienen in: Pathology & Oncology Research | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

The aim of this study was to investigate the expression of Delta-like ligand 4(DLL4) and Endoglin(CD105) labeled microvessel density(MVD) in pancreatic ductal adenocarcinoma (PDAC) and evaluate their correlation with major clinicopathologic features and patients’ survival. Forty-two pancreatic cancer and 20 normal pancreatic tissues were included in the study. Immunohistochemical staining was employed to assess the expression level of DLL4 both in tumor cells and stromal vascular endothelial cells, as well as CD105 which was used to determine MVD. The relationships of DLL4 and CD105 expression with clinicopathologic parameters and clinical outcome were evaluated. Both DLL4 and CD105-labeled microvessel were observed highly immunostained in PDAC cases, and high expression of DLL4 was positively correlated with MVD. Moreover, the high expression of DLL4 was significantly associated with histological grade, node stage and TNM stage in not only the cancer cells but also stroma; while high expression of CD105 was associated with histological grade, TNM stage, node stage and distant metastasis. In univariant analysis, patients with high expression of DLL4 and CD105 tended to significantly poorer overall survival. Both DLL4 and CD105 were overexpressed in a large proportion of patients with PDAC. The expression of DLL4 was positively correlated with CD105-labeled MVD, indicating DLL4 may involved in angiogenesis. In addition, high DLL4 and CD105 expression correlated with the poor clinical outcome and overall survival in patients with PDAC.
Literatur
2.
Zurück zum Zitat Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90CrossRefPubMed Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90CrossRefPubMed
3.
Zurück zum Zitat Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1(1):27–31CrossRefPubMed Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1(1):27–31CrossRefPubMed
4.
Zurück zum Zitat Svagzdys S, Lesauskaite V, Pavalkis D et al (2009) Microvessel density as a new prognostic marker after radiotherapy in rectal cancer. BMC Cancer 9:95PubMedCentralCrossRefPubMed Svagzdys S, Lesauskaite V, Pavalkis D et al (2009) Microvessel density as a new prognostic marker after radiotherapy in rectal cancer. BMC Cancer 9:95PubMedCentralCrossRefPubMed
5.
Zurück zum Zitat Uzzan B, Nicolas P, Cucherat M et al (2004) Microvessel density as a prognostic factor in womenwith breast cancer: a systematic reviewof the literature and meta-analysis. Cancer Res 64(9):2941–2955CrossRefPubMed Uzzan B, Nicolas P, Cucherat M et al (2004) Microvessel density as a prognostic factor in womenwith breast cancer: a systematic reviewof the literature and meta-analysis. Cancer Res 64(9):2941–2955CrossRefPubMed
6.
Zurück zum Zitat Zhao HC, Qin R, Chen XX et al (2006) Microvessel density is a prognostic marker of human gastric cancer. World J Gastroenterol 12(47):7598–7603PubMedCentralPubMed Zhao HC, Qin R, Chen XX et al (2006) Microvessel density is a prognostic marker of human gastric cancer. World J Gastroenterol 12(47):7598–7603PubMedCentralPubMed
7.
Zurück zum Zitat Han H, Silverman JF, Santucci TS et al (2001) Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis. Ann Surg Oncol 8(1):72–79CrossRefPubMed Han H, Silverman JF, Santucci TS et al (2001) Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis. Ann Surg Oncol 8(1):72–79CrossRefPubMed
8.
Zurück zum Zitat Barău A, Ruiz-Sauri A, Valencia G et al (2013) High microvessel density in pancreatic ductal adenocarcinoma is associated with high grade. Virchows Arch 462:541–546CrossRefPubMed Barău A, Ruiz-Sauri A, Valencia G et al (2013) High microvessel density in pancreatic ductal adenocarcinoma is associated with high grade. Virchows Arch 462:541–546CrossRefPubMed
9.
Zurück zum Zitat van der Zee JA, van Eijck CH, Hop WC et al (2011) Angiogenesis: a prognostic determinant in pancreatic cancer? Eur J Cancer 47(17):2576–2584CrossRefPubMed van der Zee JA, van Eijck CH, Hop WC et al (2011) Angiogenesis: a prognostic determinant in pancreatic cancer? Eur J Cancer 47(17):2576–2584CrossRefPubMed
10.
Zurück zum Zitat Kuiper P, Hawinkels LJAC, de Jonge-Muller ESM et al (2011) Angiogenic markers endoglin and vascular endothelial growth factor in gastroenteropancreatic neuroendocrine tumors. World J Gastroenterol 17(2):219–225PubMedCentralCrossRefPubMed Kuiper P, Hawinkels LJAC, de Jonge-Muller ESM et al (2011) Angiogenic markers endoglin and vascular endothelial growth factor in gastroenteropancreatic neuroendocrine tumors. World J Gastroenterol 17(2):219–225PubMedCentralCrossRefPubMed
11.
Zurück zum Zitat Zhou W, Wang G, Guo S (2013) Regulation of angiogenesis via Notch signaling in breast cancer and cancer stem cells. Biochim Biophys Acta 1836(2):304–320PubMed Zhou W, Wang G, Guo S (2013) Regulation of angiogenesis via Notch signaling in breast cancer and cancer stem cells. Biochim Biophys Acta 1836(2):304–320PubMed
12.
Zurück zum Zitat Liu Z, Fan F, Wang A et al (2014) Dll4-Notch signaling in regulation of tumor angiogenesis. J Cancer Res Clin Oncol 140(4):525–536CrossRefPubMed Liu Z, Fan F, Wang A et al (2014) Dll4-Notch signaling in regulation of tumor angiogenesis. J Cancer Res Clin Oncol 140(4):525–536CrossRefPubMed
13.
Zurück zum Zitat Chen HT, Cai QC, Zheng JM et al (2012) High expression of delta-like ligand 4 predicts poor prognosis after curative resection for pancreatic cancer. Ann Surg Oncol 19(Suppl 3):S464–S474CrossRefPubMed Chen HT, Cai QC, Zheng JM et al (2012) High expression of delta-like ligand 4 predicts poor prognosis after curative resection for pancreatic cancer. Ann Surg Oncol 19(Suppl 3):S464–S474CrossRefPubMed
14.
Zurück zum Zitat Jubb AM, Soilleux EJ, Turley H et al (2010) Expression of vascular notch ligand delta-like 4 and inflammatory markers in breast cancer. Am J Pathol 176(4):2019–2028PubMedCentralCrossRefPubMed Jubb AM, Soilleux EJ, Turley H et al (2010) Expression of vascular notch ligand delta-like 4 and inflammatory markers in breast cancer. Am J Pathol 176(4):2019–2028PubMedCentralCrossRefPubMed
15.
Zurück zum Zitat Linder S, Blåsjö M, von Rosen A et al (2001) Pattern of distribution and prognostic value of angiogenesis in pancreatic duct carcinoma:a semiquantitative immunohistochemical study of 45 patients. Pancreas 22(3):240–247CrossRefPubMed Linder S, Blåsjö M, von Rosen A et al (2001) Pattern of distribution and prognostic value of angiogenesis in pancreatic duct carcinoma:a semiquantitative immunohistochemical study of 45 patients. Pancreas 22(3):240–247CrossRefPubMed
16.
Zurück zum Zitat Mullendore ME, Koorstra JB, Li YM et al (2009) Ligand-dependent Notch signaling is involved in tumor initiation and tumor maintenance in pancreatic cancer. Clin Cancer Res 15(7):2291–2301PubMedCentralCrossRefPubMed Mullendore ME, Koorstra JB, Li YM et al (2009) Ligand-dependent Notch signaling is involved in tumor initiation and tumor maintenance in pancreatic cancer. Clin Cancer Res 15(7):2291–2301PubMedCentralCrossRefPubMed
17.
18.
Zurück zum Zitat Donnem T, Andersen S, Al-Shibli K et al (2010) Prognostic impact of Notch ligands and receptors in non-small cell lung cancer: coexpression of Notch-1 and vascular endothelial growth factor-A predicts poor survival. Cancer 116:5676–5685CrossRefPubMed Donnem T, Andersen S, Al-Shibli K et al (2010) Prognostic impact of Notch ligands and receptors in non-small cell lung cancer: coexpression of Notch-1 and vascular endothelial growth factor-A predicts poor survival. Cancer 116:5676–5685CrossRefPubMed
19.
20.
Zurück zum Zitat Oishi H, Sunamura M, Egawa S et al (2010) Blockade of Delta-like ligand 4 signaling inhibits both growth and angiogenesis of pancreatic cancer. Pancreas 39(6):897–903CrossRefPubMed Oishi H, Sunamura M, Egawa S et al (2010) Blockade of Delta-like ligand 4 signaling inhibits both growth and angiogenesis of pancreatic cancer. Pancreas 39(6):897–903CrossRefPubMed
21.
Zurück zum Zitat Sheldon H, Heikamp E, Turley H et al (2010) New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 116(13):2385–2394CrossRefPubMed Sheldon H, Heikamp E, Turley H et al (2010) New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 116(13):2385–2394CrossRefPubMed
22.
Zurück zum Zitat Jacobsen TL, Brennan K, Arias AM et al (1998) Cis-interactions between Delta and Notch modulate neurogenic signalling in Drosophila. Development 125(22):4531–4540PubMed Jacobsen TL, Brennan K, Arias AM et al (1998) Cis-interactions between Delta and Notch modulate neurogenic signalling in Drosophila. Development 125(22):4531–4540PubMed
Metadaten
Titel
Overexpressions of DLL4 and CD105 are Associated with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma
verfasst von
Liangjing Zhou
Leilai Yu
Guoping Ding
Wenchao Chen
Sixin Zheng
Liping Cao
Publikationsdatum
01.09.2015
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 4/2015
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-015-9937-4

Weitere Artikel der Ausgabe 4/2015

Pathology & Oncology Research 4/2015 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.