Influence of tumor microenvironment on prognosis in colorectal cancer: Tissue architecture-dependent signature of endosialin (TEM-1) and associated proteins.

Daniel J O’Shannessy,Jennifer Bordeaux,Lakshmi K Chandrasekaran,Nicholas C Nicolaides,Mark D Gustavson,Elizabeth B Somers

doi:10.18632/oncotarget.2108

Daniel J O’Shannessy, Jennifer Bordeaux + Show 4 more

Open Access

https://doi.org/10.18632/oncotarget.2108

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Journal: Oncotarget	Publication Date: Jun 16, 2014
Citations: 64	License type: cc-by

Affiliation: Morphotek (United States)

Abstract

Tumor survival is influenced by interactions between tumor cells and the stromal microenvironment. One example is Endosialin (Tumor Endothelial Marker-1 (TEM-1) or CD248), which is expressed primarily by cells of mesenchymal origin and some tumor cells. The expression, as a function of architectural masking, of TEM-1 and its pathway-associated proteins was quantified and examined for association with five-year disease-specific survival on a colorectal cancer (CRC) cohort divided into training (n=330) and validation (n=164) sets. Although stromal expression of TEM-1 had prognostic value, a more significant prognostic signature was obtained through linear combination of five compartment-specific expression scores (TEM-1 Stroma, TEM-1 Tumor Vessel, HIF2α Stromal Vessel, Collagen IV Tumor, and Fibronectin Stroma). This resulted in a single continuous risk score (TAPPS: TEM-1 Associated Pathway Prognostic Signature) which was significantly associated with decreased survival on both the training set [HR=1.76 (95%CI: 1.44-2.15); p<0.001] and validation set [HR=1.38 (95%CI: 1.02-1.88); p=0.04]. Importantly, since prognosis is a critical clinical question in Stage II patients, the TAPPS score also significantly predicted survival in the Stage II patient (n=126) cohort [HR=1.75 (95%CI: 1.22-2.52); p=0.002] suggesting the potential of using the TAPPS score to assess overall risk in CRC patients, and specifically in Stage II patients.

Highlights

Maintenance of epithelial tissues, including those involved in malignant diseases, requires interactions with neighboring cells, especially stromal cells
We have shown that Tumor Endothelial Marker-1 (TEM-1) and a subset of its associated pathway partners can predict outcomes of patients with colorectal cancer (CRC)
The TAPPS score described could be useful in clinical practice using standard of care therapeutic regimens to aid in predicting patient chemotherapeutic benefit, especially in Stage II patients

Summary

Introduction

Maintenance of epithelial tissues, including those involved in malignant diseases, requires interactions with neighboring cells, especially stromal cells. Experimental animal models have demonstrated that cancer invasion is stimulated by stromal microenvironments similar to those present in wound healing [5] This observation suggests that growth factors implicated in wound healing such as transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) may play a role in altering the stromal host compartment in support of cancer [6]. In both wound www.impactjournals.com/oncotarget healing and tumorigenesis, the fibroblast-to-myofibroblast transition marks the stromal alteration that leads to the biological functions of the lesion

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