title: Loss of XRCC1 confers a metastatic phenotype to melanoma cells and is associated with poor survival in patients with melanoma.
abstract: Ultraviolet (UV) radiation-induced DNA damage and genomic instability is one of the leading causes for melanoma. X-ray repair cross-complementary protein 1, XRCC1, plays a critically important role in base excision repair pathway. This study was therefore performed to analyze the correlation between XRCC1 expression, melanoma progression, and patient survival. Using a tissue microarray with a total of 119 patients with melanoma, we demonstrate that loss of XRCC1 expression is associated with the progression of disease from dysplastic nevi to primary melanoma and to metastatic melanoma. We found that the loss of XRCC1 was correlated with the progression of melanoma from AJCC stage II to stage III and with worse overall and disease-specific 5-yr and 10-yr survival of patients with melanoma. Furthermore, we also illustrate the inhibitory effect of XRCC1 on melanoma cell invasion and migration, which are the regulatory events in melanoma metastasis.
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Bhandaru
authors.forename: Magdalena
authors.initials: M
authors.lastname: Martinka
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Anand
authors.initials: A
authors.lastname: Rotte
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D004416:Dysplastic Nevus Syndrome / Q000235:genetics / Q000473:pathology; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000556:secondary*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D009367:Neoplasm Staging; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: XRCC1; cell cycle; invasion; melanoma; migration; prognosis