Vasohibin-1 Is a Poor Prognostic Factor of Ovarian Carcinoma

Abstract

Vasohibin-1 (VASH1) is an identified negative feedback inhibitor of angiogenesis induced by vascular endothelial growth factor (VEGF) in vascular endothelial cells (ECs). Expression of VASH1 has been reported not only in ECs of normal tissue, but also in ECs surrounding malignant tumors. In malignant tumors, VASH1 is also gaining attention as a prognosis prediction marker. The aim of this study is to investigate the correlation between VASH1 expression and vascular-related factors and various clinicopathological outcomes in clinical cases of ovarian carcinoma. We retrospectively analyzed clinical records of 58 patients with ovarian carcinoma. The expression patterns of VASH1 and other vascularrelated factors (CD31 as markers of microvessel density (MVD), VEGF receptor type 2 (VEGFR2), D2-40 as markers of lymphovessel density), and Ki67 (as proliferation markers of cancer cells) were examined immunohistochemically. We studied the correlation between immunohistochemical expression and overall survival. VASH1 expression pattern significantly differed between Federation of Obstetrics and Gynecology (FIGO) Stages. Numbers of VASH1-positive vessels had a significant positive correlation with MVD (Speaman's correlation coefficient (ρ) was 0.51, p < 0.001), VEGFR2-positive vessels (ρ = 0.61, p < 0.001), and percentage of Ki67 (ρ = 0.28, p = 0.034). The Cox univariable analyses revealed that the group of high VASH1 expression (> 14.6 vessels per mm 2 ) at Stages I-III is a prognostic factor (HR = 3.3, 95%CI = 0.4-8.4; p = 0.013). Our results indicate that VASH1 expression in ovarian carcinoma is significantly associated with vascular-related factors and Ki67 expression. We propose that VASH1 is a prognostic marker in ovarian carcinoma.

The Tubulin Code and Tubulin-Modifying Enzymes in Autophagy and Cancer

“…The VASH family, which includes vasohibin-1 (VASH1) and vasohibin-2 (VASH2), is a novel family of angiogenesis regulators [ 84 ] that act as tubulin-specific CCPs [ 40 , 45 ]. According to their role in angiogenesis, high expression of VASH1 and VASH2 was associated with poor clinical outcomes in gastric, ovarian, and esophageal squamous carcinoma patients [ 85 , 86 , 87 , 88 ]. Despite this, the relationship between the tubulin CCP activity of VASH1/2 and cancer progression or drug sensitivity is still a matter of debate.…”

Prognostic significance of vasohibin-1 and vasohibin-2 immunohistochemical expression in gastric cancer

“…Vasohibin expression and its impact on prognosis have been studied in patients with breast, endometrial, cervical, liver, pancreatic, colorectal, non-small cell lung, renal cell, head and neck squamous cell, esophageal squamous cell, upper urothelial, prostate, and ovarian cancers. All of these studies found that vasohibin expression (VASH1 alone, VASH2 alone, or both VASH1 and VASH2) was associated with poor prognosis, suggesting its utility as a new biomarker [18,19,[22][23][24][25][26][27][28][29][30][31][32][33][34]. In particular, the association between VASH2 expression and tumor growth has been studied in patients with pancreatic, esophageal squamous cell, and ovarian cancers [19,22,29].…”

Clinical and prognostic role of Vasohibin-1 expression in solid tumors: An evidence from a meta-analysis

“…studies were identified as meeting our inclusion criteria [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34], whose detailed information was shown in Table 2. The VASH1 relatively-low expression group (1225 individuals; 52.8%) was regarded as the control group.…”