High SHIP2 expression indicates poor survival in colorectal cancer.

Ju Yang,Yaoguang Ding,Maoying Fu,Wei Zhang,Weifei Fan,Xiaolin Pu,Feng Jin,Zhijun Ge,Xuefeng Gu,Jiang Li,Huihui Ni,Yajing Weng,Jun Wang,Ning Xu,Liang Qiu,Feng Zhan

doi:10.1155/2014/218968

Abstract

SH2-containing inositol 5′-phosphatase 2 (SHIP2), which generally regulates insulin signaling, cytoskeleton remodeling, and receptor endocytosis, has been suggested to play a significant role in tumor development and progression. However, the associations between SHIP2 expression and the clinical features to evaluate its clinicopathologic significance in colorectal cancer (CRC) have not been determined yet. In the present study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with CRC tissue microarrays (TMA) were employed to evaluate the mRNA and protein expression of SHIP2 in CRC. The results showed that SHIP2 expression in the mRNA and protein levels was significantly higher in CRC tissues than that in corresponding noncancerous tissues (both P < 0.05). The expression of SHIP2 protein in CRC was related to lymph node metastasis (P = 0.036), distant metastasis (P = 0.001), and overall survival (P = 0.009). Kaplan-Meier method and Cox multifactor analysis suggested that high SHIP2 protein level (P = 0.040) and positive distant metastasis (P = 0.048) were critically associated with the unfavorable survival of CRC patients. The findings suggested that SHIP2 may be identified as a useful prognostic marker in CRC and targeting CRC may provide novel strategy for CRC treatment.

Highlights

Colorectal cancer (CRC) is the third most common malignancy in the world, with an estimated incidence of more than 1.2 million new cases and over 600 000 deaths globally [1,2,3]
A total of 15 fresh colorectal cancer (CRC) tissues and matched tumor-adjacent noncancerous tissues were collected from the tissue bank of the Affiliated Hospital of Nantong University to perform quantitative real-time polymerase chain reaction test. 102 formalin-fixed, paraffin-embedded CRC tissues and corresponding tumoradjacent normal tissues were enrolled in this present study from the Affiliated Hospital of Nantong University from 2002 to 2005 to execute immunohistochemistry (IHC) analysis
SH2-containing inositol 5󸀠-phosphatase 2 (SHIP2) plays a substantial role in the negative regulation of insulin sensitivity [14]

Summary

Introduction

Colorectal cancer (CRC) is the third most common malignancy in the world, with an estimated incidence of more than 1.2 million new cases and over 600 000 deaths globally [1,2,3]. During the last two decades, several countries including China, South Korea, and Japan have witnessed a two- to threefold rise in incidence of CRC. In China, for example, the total number of CRC cases increased by 19.1% and 17.7% in Chinese males and females from 2000 to 2005, respectively [5, 6]. Despite the development of combined therapeutic modalities for CRC treatment, including surgical operation and combination of chemotherapy and adjuvant therapy, the overall prognosis of CRC remains unsatisfactory and the 5-year survival rate of CRC patients with metastasis is still under 10% [8, 9]. It is valuable and critical to discover molecular predictive markers for the prognosis, which would optimize the selection of therapeutic strategies and further improve patients’ survival for CRC [10]

Methods

Results

Conclusion