title: Influence of tumor microenvironment on prognosis in colorectal cancer: Tissue architecture-dependent signature of endosialin (TEM-1) and associated proteins.
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.
authors: Department of Translational Medicine and Diagnostics, Morphotek Inc., Exton, PA.
authors: Daniel J
authors: DJ
authors: O'Shannessy
authors: Department of Translational Medicine and Diagnostics, Morphotek Inc., Exton, PA.
authors: Elizabeth B
authors: EB
authors: Somers
authors: HistoRx Inc. (A subsidiary of Genoptix Medical Laboratory, Inc.), Carlsbad, CA.
authors: Lakshmi K
authors: LK
authors: Chandrasekaran
authors: Department of Translational Medicine and Diagnostics, Morphotek Inc., Exton, PA.
authors: Nicholas C
authors: NC
authors: Nicolaides
authors: HistoRx Inc. (A subsidiary of Genoptix Medical Laboratory, Inc.), Carlsbad, CA.
authors: Jennifer
authors: J
authors: Bordeaux
authors: HistoRx Inc. (A subsidiary of Genoptix Medical Laboratory, Inc.), Carlsbad, CA.
authors: Mark D
authors: MD
authors: Gustavson
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009363:Neoplasm Proteins; D011379:Prognosis; D016019:Survival Analysis; D059016:Tumor Microenvironment
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human; D009363:Neoplasm Proteins