Priority Research Papers:
Influence of tumor microenvironment on prognosis in colorectal cancer: Tissue architecture-dependent signature of endosialin (TEM-1) and associated proteins
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Daniel J. O’Shannessy1, Elizabeth B. Somers1, Lakshmi K. Chandrasekaran2, Nicholas C. Nicolaides1, Jennifer Bordeaux2, and Mark D. Gustavson2
1 Department of Translational Medicine and Diagnostics, Morphotek Inc., Exton, PA
2 HistoRx Inc. (A subsidiary of Genoptix Medical Laboratory, Inc.), Carlsbad, CA
Daniel J. O’Shannessy, email:
Keywords: Endosialin, TEM-1, CRC, tumor microenvironment, prognosis
Received: April 20, 2014 Accepted: June 14, 2014 Published: June 16, 2014
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.
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