Novel role for RGS1 in melanoma progression.
RGS1 (regulator of G protein signaling 1) encodes a member of the regulator of G protein family. Recently, RGS1 was found to be overexpressed in gene expression-profiling studies of melanoma. However, no analyses have been reported of its expression at the protein level in melanoma. In this study, the potential impact of RGS1 as a molecular prognostic marker for melanoma was assessed using immunohistochemical analysis of a melanoma tissue microarray containing primary cutaneous melanomas from 301 patients. High RGS1 expression was significantly correlated with increased tumor thickness (P=0.0083), mitotic rate (P=0.04), and presence of vascular involvement (P<0.02). Kaplan-Meier analysis demonstrated a significant association between increasing RGS1 expression and reduced relapse-free survival (P=0.0032) as well as disease-specific survival (DSS) (P=0.018) survival. Logistic regression analysis showed RGS1 overexpression to be significantly correlated to sentinel lymph node metastasis (P=0.04). Multivariate Cox regression analysis showed that increasing RGS1 immunostaining had an independent impact on the relapse-free survival (P=0.0069) and DSS (P=0.0077) of this melanoma cohort. In the analysis of DSS, RGS1 expression level was the most powerful factor predicting DSS. RGS1 immunostaining retained independent prognostic impact even when sentinel lymph node status was included in the prognostic model (P=0.0039). These results validate the role of RGS1 as a novel prognostic marker for melanoma given its impact on the survival associated with melanoma.
Rangel
Javier
J
Auerback Melanoma Research Laboratory, Cutaneous Oncology Program, UCSF Comprehensive Cancer Center, Department of Dermatology, University of California San Francisco, San Francisco, CA 94115, USA.
Nosrati
Mehdi
M
Leong
Stanley P L
SP
Haqq
Chris
C
Miller
James R
JR
Sagebiel
Richard W
RW
Kashani-Sabet
Mohammed
M
D014408:Biomarkers, Tumor / Q000032:analysis*; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D008940:Mitotic Index; D011379:Prognosis; D016016:Proportional Hazards Models; D020710:RGS Proteins / Q000032:analysis*; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D046888:Tissue Array Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D020710:RGS Proteins; C080831:RGS1 protein, human