CD44, Sonic Hedgehog, and Gli1 Expression Are Prognostic Biomarkers in Gastric Cancer Patients after Radical Resection.

Chen Jian-Hui,Wu Hui,Chen Si-Le,Zhai Er-Tao,Chen Chuang-Qi,Cai Shi-Rong,Wu Kai-Ming,He Yu-Long,Zhang Xin-Hua

doi:10.1155/2016/1013045

Abstract

Aim. CD44 and Sonic Hedgehog (Shh) signaling are important for gastric cancer (GC). However, the clinical impact, survival, and recurrence outcome of CD44, Shh, and Gli1 expressions in GC patients following radical resection have not been elucidated. Patients and Methods. CD44, Shh, and Gli1 protein levels were quantified by immunohistochemistry (IHC). The association between CD44, Shh, and Gli1 expression and clinicopathological features or prognosis of GC patients was determined. The biomarker risk score was calculated by the IHC staining score of CD44, Shh, and Gli1 protein. Results. The IHC positive staining of CD44, Shh, and Gli1 proteins was correlated with larger tumour size, worse gross type and histological type, and advanced TNM stage, which also predicted shorter overall survival (OS) and disease-free survival (DFS) after radical resection. Multivariate analysis indicated the Gli1 protein and Gli1, CD44 proteins were predictive biomarkers for OS and DFS, respectively. If biomarker risk score was taken into analysis, it was the independent prognostic factor for OS and DFS. Conclusions. CD44 and Shh signaling are important biomarkers for tumour aggressiveness, survival, and recurrence in GC.

Highlights

Due to an increased early detection rate and therapeutic advancements, the survival of gastric cancer (GC) patients has improved in the past 3 decades worldwide
To investigate the role of the tumour stem cell biomarker CD44 and Sonic Hedgehog (Shh) signaling pathway in GC tumour, we evaluated the levels of CD44, Shh, and Gli1 protein in tumour tissues using immunohistochemistry (IHC) (Figure 1) and the positive stainings of Gli1, Shh, and CD44 protein were mainly localized in the nucleus, cytoplasm, and cell membrane, respectively
We found that 57.8% (59/101), 71.3% (72/101), and 57.8% (59/101) GC tumour specimens stained positively for CD44, Shh, and Gli1 protein, respectively

Summary

Introduction

Due to an increased early detection rate and therapeutic advancements, the survival of gastric cancer (GC) patients has improved in the past 3 decades worldwide. CD44, widely accepted as a CSCs marker for gastric cancer in many studies [4,5,6], is involved in cell-cell adhesion, cell-matrix interactions, and tumour metastasis [4]. Several studies have demonstrated that increased CD44 expression activates several signalling pathways related to cancer progression and metastasis, including Shh pathway [10]. Song et al [10] demonstrated that the Shh pathway is essential for maintenance of human gastric cancer CSCs in vitro. The clinical impact and interaction between the Shh pathway and CD44 expression in gastric cancer

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