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LOXL2 Is highly expressed in cancer-associated fibroblasts and associates to poor colon cancer survival

Other TitlesLOXL2 in colon cancer prognosis
AuthorsTorres, Sofía ; García-Palmero, Irene ; Bartolomé, Rubén Álvaro ; Padilla, Guillermo ; Peláez-García, Alberto ; López-Lucendo, María F. ; Casal, J. Ignacio
KeywordsPrognostic biomarker
Cancer-associated fibroblasts
Colon cancer
Issue Date1-Nov-2015
PublisherAmerican Association for Cancer Research
CitationClin Cancer Res 21(21) 4892-902 (2015)
AbstractPurpose: Cancer-associated fibroblasts (CAF) are major mediators in tumor microenvironment. We investigated the changes in protein expression in colon cancer–associated fibroblasts compared with normal fibroblasts (NF) in the context of searching for prognostic biomarkers, particularly for stage II patients.
Experimental Design: CAFs and NFs isolated from colon cancer patients were used to identify differentially expressed proteins using quantitative proteomics. Stromal expression of deregulated proteins was analyzed by IHC. Prognostic impact was studied using external gene-expression datasets for training,then quantitative PCR and IHC for validation in different cohorts of patients. Combined datasets were used for prediction of risk assessment at stages II and III.
Results: A desmoplastic signature composed of 32 proteins,highly specific for stromal components in colon cancer, was identified. These proteins were enriched for extracellular matrix organization components, TGFb signaling pathway, fibrosis, and wound-healing proteins. The expression in CAFs of 11 upregulated proteins and four downregulated proteins, selected for biomarker validation, was verified by orthogonal techniques.LOXL2 displayed a high prognostic impact by using external independent datasets and further validation in two different cohorts of patients. High expression of LOXL2 was associated with higher recurrence P ¼ 0.001 HR, 5.38 [95% confidence interval (CI), 1.70–17.01] and overall survival P ¼ 0.001 HR,8.52 (95% CI, 1.90–38.29). IHC analysis revealed a prognostic value for LOXL2 in stage II patients.
Description36 p.-5 fig.-1 tab. Torres, Sofía et al.
Publisher version (URL)http://dx.doi.org/ 10.1158/1078-0432.CCR-14-3096
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