Expression of Vasohibin-2 in Pancreatic Ductal Adenocarcinoma Promotes Tumor Progression and is Associated with a Poor Clinical Outcome

被引:23
作者
Kim, Jung-Chul [1 ]
Kim, Kyung-Tae [2 ]
Park, Jong-Tae [3 ]
Kim, Hyun-Jong [1 ]
Sato, Yasufumi [4 ]
Kim, Hyung-Seok [3 ]
机构
[1] Chonnam Natl Univ, Sch Med, Dept Surg, Div Hepatobiliary Pancreat Surg, Gwangju 501757, South Korea
[2] Inje Univ, Ilsan Paik Hosp, Dept Anesthesiol & Pain Med, Goyang, South Korea
[3] Chonnam Natl Univ, Sch Med, Dept Forens Med, Gwangju 501757, South Korea
[4] Tohoku Univ, Inst Dev Aging & Canc, Dept Vasc Biol, Sendai, Miyagi 980, Japan
基金
新加坡国家研究基金会;
关键词
Pancreatic ductal adenocarcinoma; Vasohibin-2; tumor angiogenesis; Prognosis; CELL LUNG-CANCER; PROGNOSTIC-SIGNIFICANCE; ANGIOGENESIS; GROWTH; CARCINOMA; LOCALIZATION; BIOMARKERS; FAMILY;
D O I
10.5754/hge141015
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
This study aimed to assess the expression of vasohibin-2 (VASH2) in pancreatic ductal adenocarcinoma (PDAC) as a marker of tumor aggressiveness and its impact on tumor angiogenesis, proliferation, and clinical outcome. We examined the expression of the VASH2 gene in human pancreatic cell lines PANC-1 and MiaPaCa-2 by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunocytochemistry. Fifty samples from patients with PDAC were immunostained with VASH2, CD34, and Ki-67 antibodies. Further, the immunoreactivity of VASH2 correlated with the pathological features, including microvessel density (MVD), tumor cell proliferation (Ki-67 labeling index), and survival. Forty-seven of the 50 samples from PDAC patients showed immunoreactivity for VASH2 along the tumor cell cytoplasm. Among the VASH2-positive samples, 22 were categorized as high VASH2 expression group, and this group had statistical significance with pN stage (p = 0.006), UICC stage (p = 0.033), tumor proliferation (p < 0.001), and MVD (p = 0.017). Moreover, patients with high VASH2 expression showed worse prognosis compared to those showing low VASH2 expression (overall logrank p = 0.003). Thus, our results suggested that overexpression of VASH2 accelerated the pace of tumor development toward a more serious malignant phenotype and was associated with a poor clinical outcome. VASH2 may be an important novel target for the management of PDAC after surgery.
引用
收藏
页码:251 / 256
页数:6
相关论文
共 29 条
[1]   Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer [J].
Ansari, D. ;
Rosendahl, A. ;
Elebro, J. ;
Andersson, R. .
BRITISH JOURNAL OF SURGERY, 2011, 98 (08) :1041-1055
[2]   Effects of estrogen depletion on angiogenesis in estrogen-receptor-positive breast carcinoma - an immunohistochemical study of vasohibin-1 and CD31 with correlation to pathobiological response of the patients in neoadjuvant aromatase inhibitor therapy [J].
Chan, Monica S. M. ;
Wang, Lin ;
Chanplakorn, Niramol ;
Tamaki, Kentaro ;
Ueno, Takayuki ;
Toi, Masakazu ;
Loo, Wings T. Y. ;
Chow, Louis W. C. ;
Suzuki, Takashi ;
Sasano, Hironobu .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2012, 16 :S69-S78
[3]   Pathology of pancreatic ductal adenocarcinoma: Facts, challenges and future developments [J].
Esposito, Irene ;
Konukiewitz, Bjoern ;
Schlitter, Anna Melissa ;
Kloeppel, Guenter .
WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (38) :13833-13841
[4]  
Fujioka S, 2001, CANCER, V92, P1788, DOI 10.1002/1097-0142(20011001)92:7<1788::AID-CNCR1695>3.0.CO
[5]  
2-Z
[6]  
Hwang Insang, 2012, Chonnam Med J, V48, P174, DOI 10.4068/cmj.2012.48.3.174
[7]   Prognostic significance of angiogenesis in human pancreatic cancer [J].
Ikeda, N ;
Adachi, M ;
Taki, T ;
Huang, C ;
Hashida, H ;
Takabayashi, A ;
Sho, M ;
Nakajima, Y ;
Kanehiro, H ;
Hisanaga, M ;
Nakano, H ;
Miyake, M .
BRITISH JOURNAL OF CANCER, 1999, 79 (9-10) :1553-1563
[8]   Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis [J].
Jamieson, Nigel B. ;
Carter, C. Ross ;
McKay, Colin J. ;
Oien, Karin A. .
CLINICAL CANCER RESEARCH, 2011, 17 (10) :3316-3331
[9]   Correlation between cyclooxygenase-2 and tumor angiogenesis in non-small cell lung cancer [J].
Kim, HS ;
Youm, HR ;
Lee, JS ;
Min, KW ;
Chung, JH ;
Park, CS .
LUNG CANCER, 2003, 42 (02) :163-170
[10]  
Kim HS, 2012, INT J CLIN EXP PATHO, V5, P754