Novel Role for RGS1 in Melanoma Progression

Auerback Melanoma Research Laboratory, Cutaneous Oncology Program, UCSF Comprehensive Cancer Center, Department of Dermatology, University of California San Francisco, San Francisco, CA 94115, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 06/2008; 32(8):1207-12. DOI: 10.1097/PAS.0b013e31816fd53c
Source: PubMed


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.

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    • "Single-nucleotide polymorphisms in this gene have been associated with spondylarteritis, type 1 diabetes mellitus and celiac disease [20]–[22]. In addition they are an independent prognostic marker of disease survival in melanomas [23]. So far, there is no clear association with atherogenesis or CVD. "
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    Full-text · Article · Feb 2012 · PLoS ONE
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    • "As each probe has a unique length due to the stuffer sequence, electrophoresis conveniently separates and quantifies the amount of PCR product indicating the DNA copy number [24]. Mutation-specific MLPA combines copy number detection and hot-spot mutations in a single assessment [54]. "
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    • "Family A/RZ RGS17/RGSZ2 " in prostate cancer [99]; " in lung cancer [99] RGS19/GAIP " in ovarian cancer [53]; regulates wnt/b-catenin signaling [100]; binding partner GIPC down-regulated in primary kidney tumors, colorectal tumors, gastric cancer, and prostate cancer [101] RGS20/RGSZ1 " in melanoma [102] Family B/R4 RGS1 " in melanoma [55]; " in head and neck squamous cell carcinoma [103]; " in adult T-cell leukemia [70]; " in renal cell carcinoma [54]; " in ovarian cancer [54]; " in cervical cancer [104]; " in mantle cell lymphoma [81] RGS2 # in ovarian cancer [53]; " in breast cancer [65]; " in fibrolamellar carcinoma [105]; # in prostate cancer [17]; # in acute myeloid leukemia [69]; " in mantle cell lymphoma [81] RGS3 " in docetaxel resistant breast cancers [106]; " associated with enhanced glioma cell motility [71]; " in soft tissue sarcomas [107] RGS4 " associated with enhanced glioma cell motility [71]; " in thyroid carcinoma [66]; # in ovarian cancer [53] RGS5 " in hepatocellular carcinoma [61]; " in breast cancer, melanoma, multiple myeloma, ovarian cancer, and acute myeloid leukemia [98]; " in fibrolamellar carcinoma [105] RGS8 N/A RGS13 # in mantle cell lymphoma [59]; " in B-and T-cell lymphoma [108] RGS16 " in pediatric high hyperdiploid acute lymphoblastic leukemias [109]; " in pineal parenchymal tumors [110]; p53 target gene in colorectal cancer [111] RGS18 N/A "
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