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.
Department of Cellular and Molecular Medicine, George E. Palade Laboratories, University of California, San Diego School of Medicine, La Jolla, CA 92093-0651, USA.
Mikel
M
Garcia-Marcos
Barbara H
BH
Jung
Jason
J
Ear
Betty
B
Cabrera
John M
JM
Carethers
Pradipta
P
Ghosh
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