KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis
| Autor: | José A. Campillo, M. Rocío Álvarez-López, M. Rocío López-Álvarez, Jorge A. Martínez-Escribano, R.M. Blanco-García, Manuel Muro, Ana M. García-Alonso, María R. Moya-Quiles, Jose Miguel Bolarín, Isabel Legaz, Alfredo Minguela, Beatriz Las Heras, Helios Martínez-Banaclocha |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Skin Neoplasms Genotype Immunology Sentinel lymph node Human leukocyte antigen HLA-C Antigens Biology Polymerase Chain Reaction Metastasis HLA-C Genetics medicine Biomarkers Tumor Humans Genetic Predisposition to Disease Receptor Melanoma Polymorphism Single-Stranded Conformational Genetic Variation Middle Aged medicine.disease Prognosis Receptors KIR2DL3 Lymphatic Metastasis Cancer research Female CD8 |
| Zdroj: | Immunogenetics. 65(5) |
| ISSN: | 1432-1211 |
| Popis: | Natural killer and CD8(+) T cells are believed to be involved in the immune protection against melanoma. Their function may be regulated by a group of receptors defined as killer immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands. In this study, we analyzed the influence of KIR genes and KIR/HLA-I combinations on melanoma susceptibility and/or prognosis in a Spanish Caucasian population. For this purpose, KIR genotyping by PCR-SSP and HLA-C genotyping by reverse PCR-SSO were performed in 187 melanoma patients and 200 matched controls. We found a significantly low frequency of KIR2DL3 in nodular melanoma (NM) patients (P = 0.001) and in ulcerated melanoma patients (P0.0001). Similarly, the KIR2DL3/C1 combination was significantly decreased in melanoma patients (Pc = 0.008) and in patients with sentinel lymph node (SLN) melanoma metastasis (Pc = 0.002). Multivariate logistic regression models showed that KIR2DL3 behaves as a protective marker for NM and ulcerated melanoma (P = 0.02, odds ratio (OR) = 0.14 and P = 0.04, OR = 0.28, respectively), whereas the KIR2DL3/C1 pair acts as a protective marker for melanoma (P = 0.017, OR = 0.54), particularly superficial spreading melanoma (P = 0.02, OR = 0.52), and SLN metastasis (P = 0.0004, OR = 0.14). In contrast, the KIR2DL3(-)/C1C2 genotype seems to be correlated with NM and ulceration. We also report that the KIR2DL1(+)/S1(-)/C2C2 genotype is associated with susceptibility to melanoma and SLN metastasis. Altogether, the study of KIR2D genes and HLA-C ligands may help in assessing cutaneous melanoma risk and prognosis. |
| Databáze: | OpenAIRE |
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