Expression of vasohibin-2 in pancreatic ductal adenocarcinoma promotes tumor progression and is associated with a poor clinical outcome.
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.
Jung-Chul
JC
Kim
Kyung-Tae
KT
Kim
Jong-Tae
JT
Park
Hyun-Jong
HJ
Kim
Yasufumi
Y
Sato
Hyung-Seok
HS
Kim
D000368:Aged; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
D042501:Angiogenic Proteins; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012333:RNA, Messenger; C574858:VASH2 protein, human