Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer

Zhang,Jinxiu; Liu,Kecheng; Peng,Peng; Li,Siman; Ye,Zhe; Su,Yingjie; Liu,Shiquan; Qin,Mengbin; Huang,Jiean

doi:10.3892/ol.2019.10417

Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer

Authors:
- Jinxiu Zhang
- Kecheng Liu
- Peng Peng
- Siman Li
- Zhe Ye
- Yingjie Su
- Shiquan Liu
- Mengbin Qin
- Jiean Huang
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Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, P.R. China
Published online on: May 30, 2019 https://doi.org/10.3892/ol.2019.10417
Pages: 1163-1170
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Unlike endothelium‑dependent vasculature, vasculogenic mimicry (VM) is an alternative type of blood supply in tumors that is frequently associated with poor patient outcome. Nectin‑4 serves a vital role in the formation and maintenance of adherens junctions; integrin β‑1 (ITGB1) promotes tumor invasion, metastasis and VM formation. In the present study, the analysis of nectin‑4 mRNA expression in a database of The Cancer Genome Atlas (TCGA) was combined with that of another non‑overlapping cohort of 68 patients with CRC. TCGA data were used to examine nectin‑4 mRNA expression in CRC and its correlation with the clinicopathological features of patients. Data from the non‑overlapping cohort of patients was used to determine nectin‑4 and ITGB1 protein expression in CRC by immunohistochemical (IHC) staining. Cluster of differentiation 34/periodic acid‑Schiff double staining was performed to validate the presence of VM formation. The association with, and significance of combining nectin‑4, ITGB1 protein expression and VM formation for predicting patient prognosis was evaluated. The TCGA dataset demonstrated that nectin‑4 mRNA was upregulated in CRC, which was significantly relate to lymph node metastasis (P=0.0017), distant metastasis (P=0.0045), and tumor‑node‑metastasis (TNM) stage (P=0.0015). Of the 68 patients analyzed by IHC staining, 48 (70.6%) were positive for nectin‑4, 46 (67.6%) for ITGB1 and 17 (25%) for VM formation. Nectin‑4 protein expression was associated with ITGB1 protein expression (P<0.01) and VM formation (P<0.05). Nectin‑4, ITGB1 expression and VM formation were associated with distant metastasis stage (P<0.05) and TNM stage (P<0.05). Based on these findings it was concluded that nectin‑4 was upregulated in CRC tissues compared with normal mucosal tissues, and was associated with ITGB1 expression and VM formation. Furthermore, nectin‑4 and ITGB1 protein expression, together with VM formation may be used to predict poor prognosis in CRC.

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