Priority Research Papers:
Influence of tumor microenvironment on prognosis in colorectal cancer: Tissue architecture-dependent signature of endosialin (TEM-1) and associated proteins
Metrics: PDF 1287 views | HTML 1110 views | ?
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.