Expression of GIV/Girdin, a metastasis-related protein, predicts patient survival in colon cancer.
Metastasis accounts for the majority of cancer-related deaths. Accurate prediction of metastatic 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-nucleotide exchange factor motif that activates Gαi. 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 colorectal cancers. We conclude that GIV-fl is a novel metastasis-related protein and an independent adverse prognosticator that may serve as a useful adjunct to traditional staging strategies in colorectal carcinoma.
Garcia-Marcos
Mikel
M
Department of Cellular and Molecular Medicine, George E. Palade Laboratories, University of California, San Diego School of Medicine, La Jolla, CA 92093-0651, USA.
Jung
Barbara H
BH
Ear
Jason
J
Cabrera
Betty
B
Carethers
John M
JM
Ghosh
Pradipta
P
D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C502451:CCDC88A protein, human; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins