Polimorfismo ins/del 14pb, alelos do gene HLA-G, expressão de sHLA-G e neoplasia intra-epitelial cervical de graus ll(NICll) e III (NICIII)

Abstract

Resumo: O cancer cervical (CC) e o segundo cancer que mais afeta mulheres no mundo todo, ele progride a partir de lesoes no cervix uterino causadas pelo virus HPV, estas lesoes sao denominadas neoplasias intraepiteliais cervicais (NIC). As NICs são classificadas em lesao e baixo grau (NIC I) e lesoes de alto grau (NIC II e III). O desenvolvimento do CC depende da persistencia do virus no organismo e esta persistencia esta diretamente relacionada com a eficiencia da resposta imune contra as celulas infectadas. O antigeno leucocitario humano (HLA)-G e um gene HLA de classe I nao classico que apresenta um papel imunorregulatorio. Ele e capaz de inibir a resposta imune quando interage com receptores inibitorios presentes nas celulas Natural Killer e em Linfocitos T. A proteina HLA-G pode ser expressa na forma ligada a membrana celular, ou soluvel (sHLA-G). A expressao de HLA-G ja foi relacionada com diversas patologias e diferentes tipos de canceres como uma estrategia de escape do sistema imune. Neste estudo o objetivo foi investigar a associacao de polimorfismos do gene HLA-G e sua expressao soluvel com o desenvolvimento de lesoes cervicais. A amostra constitui de 100 mulheres diagnosticadas com NIC II, 101 NIC III, e 106 mulheres saudaveis, negativas para NIC. Foi feito a tipagem alelicas para o gene HLA-G e para o polimorfismo de 14 pb presente no exon 8 deste gene; alem disso foi realizada a quantificacao serica de sHLA-G. Nao foi registrada associacao entre a frequencia dos alelos identificados na amostra, ou do polimorfismo de 14 pb e a quantificacao de sHLA-G com predisposicao ou protecao ao desenvolvimento de lesoes cervicais. Tambem nao foi possivel definir associacoes entre os niveis sericos de sHLA-G com os alelos, ou com a presenca ou ausencia dos 14 pb. Palavras chave: HLA-G, sHLA-G, HPV, NIC e cancer cervical.

Abstract: Cervical cancer (CC) is the second cancer that most affects women worldwide, it progresses from lesions in the uterine cervix caused by HPV virus, these lesions are called cervical intraepithelial neoplasia (CIN). CINs are classified in low-grade (CIN I) and high-grade lesions (CIN II and III). The development of the CC depends on the persistence of the virus in the body and this persistence is directly related to the efficiency of the immune response against infected cells. Human leukocyte antigen (HLA)-G is an HLA class I non-classic that presents an immunoregulatory role. It is able to inhibit the immune response when interacting with inhibitory receptors present on natural killer cells and T lymphocytes The HLA-G protein can be expressed in the membrane bound form, or soluble (sHLA-G). The expression of HLA-G has been associated with several diseases and different types of cancers as a strategy to escape from the immune system. In this study the aim was to investigate the association of polymorphisms of the HLA-G gene and its soluble expression with the development of cervical lesions. The sample consisted of 100 women diagnosed with CIN II, 101 with CIN III, and 106 healthy women negative for CIN. Allele typing for the gene HLA-G and for the 14 bp polymorphism present in exon 8 of this gene was done, also serum sHLA-G was quantified. No association was recorded between the frequency of the alleles identified in the sample, or 14 bp polymorphism and quantification of sHLA-G with predisposition or protection to the development of cervical lesions. Nor was it possible to define associations between serum levels of sHLA-G with the alleles, or the presence or absence of 14 bp. Keywords: HLA-G, sHLA-G, HPV, NIC and cervical cancer.