title: A novel molecular marker of prognosis in colorectal cancer: Vasohibin-1.
abstract: Vasohibin-1 has been recently detected in endothelial cells and identified as a negative feedback regulator of angiogenesis induced by VEGF-A. However, the expression of Vasohibin-1 in colorectal cancer and its correlations with VEGF-A, microvessel density (MVD), and the prognosis of the patients remain unclear. In this study, Vasohibin-1 and VEGF-A expression were measured in 132 paraffin-embedded tissues of colorectal cancer by immunohistochemistry and Western blot, as well as in colon cancer cell lines with different metastatic potential and in normal colon cell by Western blot and real-time PCR. MVD was measured by counting CD34 positive clusters in a single field of view with the most intensive neovascularization of colon cancer tissues. The correlation between the expression of Vasohibin-1, VEGF-A, MVD, clinicopathological features, and prognosis was analyzed. We found that Vasohibin-1 and VEGF-A proteins were expressed in 88.64 % (117/132) and 84.09 % (111/132) colorectal cancer tissues, respectively. Strongly positive correlations were found between Vasohibin-1, VEGF-A expression, and MVD in the colorectal cancer tissues (Vasohibin-1 vs.
  r = 0.688, P < 0.001; Vasohibin-1 vs. MVD: r = 0.483, P < 0.001; VEGF-A vs. MVD: r = 0.491, P < 0.001). Vasohibin-1 expression has significant positive correlation with pathological TNM stage (P = 0.001), tumor stromal invasion (P = 0.004), lymph node status (P = 0.003), and distant metastasis (P = 0.033), but no correlation with tumor differentiation (P = 0.756). The patients with high Vasohibin-1 expression had significantly worse overall survival (OS) and progression-free survival (PFS) than those with low Vasohibin-1 expression (OS: P = 0.001; PFS: P = 0.003). In addition, Vasohibin-1 protein expression is an independent risk factor affecting OS and PFS. Therefore, we conclude that Vasohibin-1 is a clinically relevant predictor of patient prognosis in colorectal cancer. Vasohibin-1 might become a new biomarker and provide additional prognostic information in patients with colorectal cancer.
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
authors.forename: Yichao
authors.initials: Y
authors.lastname: Yan
authors.forename: Zhanlong
authors.initials: Z
authors.lastname: Shen
authors.forename: Yingjiang
authors.initials: Y
authors.lastname: Ye
authors.forename: Kewei
authors.initials: K
authors.lastname: Jiang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Shen
authors.forename: Harri
authors.initials: H
authors.lastname: Mustonen
authors.forename: Pauli
authors.initials: P
authors.lastname: Puolakkainen
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C493181:VASH1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A