Clinicopathological and Prognostic Significance of α5β1-integrin and MMP-14 Expressions in Colorectal Cancer

Abstract

The purpose of this study was to evaluate the association of expression level of α5β1-integrin and MMP-14 with clinicopathologic features and prognosis in colorectal cancer (CRC). The expressions of α5β1-integrin and MMP-14 in normal colorectal mucosa and CRC tissue were detected with immunohistochemistry. We estimated the five-year survival rate by the Kaplan-Meier method. The positive expressions rates of α5β1-integrin and MMP-14 in CRC tissue were 60.6% and 63.3% respectively, and there were significant differences on their positive expression rates between in CRC tissue and in normal colorectal mucosa(P<0.05). The expression rates of α5β1-integrin and MMP-14 in patients with poor histological differentiation, lymph node metastasis and high clinical staging were heightened. There was a significant difference (P<0.05) on the five-year survival rate for α5β1-integrin expression, which was 44.6% in positive groups and 75.5% in negative groups. And there was a significant difference (P<0.05) on the five-year survival rate for MMP-14 expression, which was 48.2% in positive group and 73.1% in negative group. The expression of α5β1-integrin and MMP-14 is correlated with the progression and metastasis of CRC, and α5β1-integrin and MMP-14 may be used as prognostic markers in CRC.Key words: CRC, immunohistochemistry, prognosis, survival CRC is the third most common cancer worldwide [1]. CRC is a cause of significant morbidity and cancer-related mortality in China both men and women. More than 17 million new cases of CRC were reported every year in China mainland. Despite recent treatment options and prognosis for patients with advanced CRC have improved through the development of novel drugs, progress in the treatment of CRC has been limited [2,3]. Most newly diagnosed patients will present with incurable disease, and have a median survival of less than 1 year. If metastasis has occurred, patient five-year survival rate after surgery falls dramatically from 90% to less than 10% [4]. It is, therefore, important to increase our understanding of the molecular changes leading to development, spread and metastasis of CRC and to identify potentially prognostic and predictive biomarkers for the disease.The conspicuous characteristic of malignant tumor is invasion and metastasis. To date, it is now clear that adhesive interaction play a critical role in the process of metastatic tumor dissemination [5].Cell adhesion molecules (CAMs) are involved in cell-cell and cell-extracellular matrix(ECM) binding, a highly complex process [6]. Integrins are the major adhesive molecules in cells and have been associated with metastasis of cancer cells. The integrins , a superfamily of heterodimer cell surface glycoprotein receptors composed of distinct α and β subunits [7], were originally described as cell adhesion receptors, but their functions in cell behavior including motility and invasion and their interactions with classical growth factor receptor signaling pathways have been increasingly recognized in the past few years [8]. Inte...

Inhibiting the SUMO Pathway Represses the Cancer Stem Cell Population in Breast and Colorectal Carcinomas

“…Further studies have demonstrated that MMP14 contributes to tumor growth and invasion through a critical role in altering tumor cell shape and establishing a reactive stroma that supports invasion (Vosseler et al., 2009). MMP14 has been shown to facilitate cell invasion and metastasis in a wide variety of cancer types, and its expression is associated with an unfavorable outcome in breast cancer (Jiang et al., 2006), colorectal cancer (Yang et al., 2013), neuroblastoma (Xiang et al., 2015), nasopharyngeal carcinoma (Zhao et al., 2015), small cell lung cancer (Wang et al., 2014), and mammary phyllodes tumors (Kim et al., 2012). The current results provide support for the ability to repress MMP14 expression and affect cell invasion and metastasis through the therapeutic development of SUMO inhibitors.…”

MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies

“…Of these 546 studies, we excluded 525 that did not meet the selection criteria. After reviewing the full text of the remaining 21 studies, we ultimately included 11 studies [11][12][13][14][15][16][17][18][19][20][21] in the final analysis. Ten studies were excluded from the final review for these reasons: (1) insufficient survival data (n=8) [23][24][25][26][27][28][29][30] and (2) MT1-MMP expression was not measured by immunohistochemistry (n =2) [31,32].…”

miRNA-337-3p inhibits gastric cancer progression through repressing myeloid zinc finger 1-facilitated expression of matrix metalloproteinase 14

“…In addition, MMP-14 contributes to pro-angiogenic responses through facilitating the expression of vascular epidermal growth factor ( VEGF ) and releasing bioactive ECM products [4]. High MMP-14 expression has been documented in most types of human malignancies, including colon cancer [5], breast cancer [6], ovary cancer [7], and skin cancer [8], and its elevated expression is associated with tumor invasion and metastasis [9]. Previous studies have shown that MMP-14 is highly expressed in gastric cancer, and is correlated with poor outcome of patients [10], suggesting the importance of MMP-14 in the progression of gastric cancer.…”