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Expression of GIV/Girdin, a metastasis‐related protein, predicts patient survival in colon cancer
Author(s) -
GarciaMarcos Mikel,
Jung Barbara H.,
Ear Jason,
Cabrera Betty,
Carethers John M.,
Ghosh Pradipta
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-167304
Subject(s) - colorectal cancer , metastasis , hazard ratio , medicine , oncology , microsatellite instability , biomarker , cancer , hepatocellular carcinoma , cancer research , pathology , biology , allele , confidence interval , gene , genetics , microsatellite
Metastasis accounts for the majority of cancer‐related deaths. Accurate prediction of meta‐static potential of tumors has been elusive, and the search for clinically useful markers continues. We previously reported that GIV/Girdin triggers tumor cell migration by virtue of a C‐terminal guanine‐nucle‐otide exchange factor motif that activates Gai. Here we identify GIV as a metastasis‐related protein whose full‐length transcript (GIV‐fl) is expressed exclusively in highly invasive colon, breast, and pancreatic carcinoma cells and not in their poorly invasive counterparts. A prospective, exploratory biomarker study conducted on a cohort of 56 patients with stage II colorectal cancer revealed a significant correlation between GIV‐fl expression in tumor epithelium and shortened metastasis‐free survival. Survival rate for patients with GIV‐fl‐positive tumors is significantly reduced compared with the patients with GIV‐fl‐negative tumors [ P <0.0001;hazard ratio=0.076;CI=0.052–0.30 (95%)]. At the 5‐yr mark, survival is 100% in the GIV‐fl‐negative group and 62 ± 9% (mean± se; P =6×10 ‐5 ) in the GIV‐fl‐positive group. Furthermore, GIV‐fl expression predicts a risk of mortality independent of the microsatellite stability status, a well‐established prognosticator of colo‐rectal cancers. We conclude that GIV‐fl is a novel metastasis‐related protein and an independent adverse prognos‐ticator that may serve as a useful adjunct to traditional staging strategies in colorectal carcinoma.—Garcia‐Marcos, M., Jung, B. H., Ear, J., Cabrera, B., Carethers, J. M., Ghosh, P. Expression of GIV/Girdin, a metastasis‐related protein, predicts patient survival in colon cancer. FASEB J. 25, 590–599 (2011). www.fasebj.org