AUTHOR=Coto-Llerena Mairene , Ercan Caner , Kancherla Venkatesh , Taha-Mehlitz Stephanie , Eppenberger-Castori Serenella , Soysal Savas D. , Ng Charlotte K. Y. , Bolli Martin , von Flüe Markus , Nicolas Guillaume P. , Terracciano Luigi M. , Fani Melpomeni , Piscuoglio Salvatore 

TITLE=High Expression of FAP in Colorectal Cancer Is Associated With Angiogenesis and Immunoregulation Processes

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00979

DOI=10.3389/fonc.2020.00979

ISSN=2234-943X

ABSTRACT=Fibroblast activation protein α (FAP) plays an important role in tissue remodeling and helps
tumor cells invade surrounding tissue. We sought to investigate FAP as a prognostic molecular
marker in colorectal cancer (CRC) using immunohistochemical and transcriptomic data. FAP
expression and clinicopathologic information were obtained from The Cancer Genome Atlas
dataset. FAP association with tissue cellular heterogeneity landscape was explored using xCell
method. FAP protein expression was evaluated in a cohort of 92 CRCs and 19 non-tumoral
tissue. FAP was found upregulated in tumors both at the mRNA and protein levels and its
expression was associated with advanced stages, poor survival and consensus molecular
subtype 4. FAP expression was associated with angiogenesis and collagen-degradation. We
observed an enrichment in immune-cell process-related genes associated with FAP
overexpression. CRCs with high-FAP expression display an inflamed phenotype enriched for
macrophages and monocytes. Those tumors showed enrichment for Treg populations and
depletion of Th1 and natural killer T cells, pointing to an immunosuppressive environment.
CRCs with high levels of stromal FAP are associated with aggressive disease progression and
survival. Our results suggest other roles of FAP in tumor progression such as modulation of
angiogenesis and immunoregulation in the tumor microenvironment.