RESUMO
Emerging evidence indicated that changes in DNA methylation early in breast cancer (BC) development might be clinically relevant for therapeutic decisions. Through analysis of whole-genome gene expression microarray and DNA methylation microarray, we explored genes with abnormal DNA methylation in BC for early detection. Firstly, human BC tissues and adjacent non-cancerous tissues were collected from nine BC patients. Gene expression microarray sequencing was conducted for identifying differentially expressed genes and DNA methylation microarray sequencing for differentially methylated genes in BC. Differentially expressed genes and methylated genes in BC were further explored using the Cancer Genome Atlas database. The correlation between DNA methylation and gene expression was illustrated by multiple comparisons. In other 60 clinical samples, methylation specific polymerase chain reaction (PCR) and reverse transcription quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC and adjacent non-cancerous tissues. In total, 1680 upregulated genes and 1249 downregulated genes were determined in BC. Chromosome 16 and 17 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in each gene region. Chromosome 19 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in the exoniensis 1, untranslated region-5 and transcriptional start site 200 gene regions. In other 60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA methylation and decreased gene expression in BC. MCF7 cells treated with RG108 showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1 were identified with increased DNA methylation and decreased gene expression in BC, which may serve as biomarkers in early BC detection.
Assuntos
Neoplasias da Mama/genética , Metilação de DNA/genética , Detecção Precoce de Câncer , Genoma Humano/genética , Proteínas de Homeodomínio/genética , Fator de Crescimento Insulin-Like I/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fatores de Transcrição/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Metilação de DNA/efeitos dos fármacos , Bases de Dados de Ácidos Nucleicos , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Células MCF-7 , Pessoa de Meia-Idade , Ftalimidas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Transcriptoma/genética , Triptofano/análogos & derivados , Triptofano/farmacologia , Regulação para Cima/genéticaRESUMO
OBJECTIVE: To analyze the status of HLA-DPA1 and DPB1 matching for unrelated donor-recipient pairs matched at high-resolution allele level for HLA-A, B, C, DRB1 and DQB1 loci. METHODS: A total of 76 unrelated donor-recipient pairs matching at allele level for HLA-A, B, C, DRB1 and DQB1 loci were subjected to HLA-DPA1 and DPB1 sequence-based typing (SBT). HLA-DPA1and DPB1 matching status at high-resolution allelic level was also analyzed. RESULTS: The allelic identity ratio for single HLA-DPA1 and DPB1 were 17.1% and 9.2%, respectively. HLA-DPA1 and DPB1 allelic identity ratio were both very low. The majority of unrelated donor-recipient pairs (73.7%) had an incompatibility at 1 HLA-DPA1 allele, 9.2% of pairs had an incompatibility at 2 DPA1 alleles. As for the high-polymorphic HLA-DPB1 gene, 57.9% of studied donor-recipient pairs had an incompatibility at 1 HLA-DPB1 allele, almost 1/3 (32.9%) of them were completely incompatible. When HLA-DPA1 and DPB1 genes were analyzed together, the donor-recipient pairs matched at 2/4 was the most common (51.4%), 4/4 allelic complete matched pairs accounted for 5.6%, and 0/4 matched pairs accounted for 8.3%. CONCLUSION: Our results indicated that the ratio of HLA-DPA1 and DPB1 complete match in the unrelated donor-recipient pairs matching at allelic level for HLA-A, B, C, DRB1 and DQB1 loci were very low. The effect of HLA-DPA1 and DPB1 matching status on clinical unrelated stem cell transplantation still needs to be elucidated.
Assuntos
Cadeias alfa de HLA-DP/genética , Cadeias beta de HLA-DP/genética , Cadeias beta de HLA-DQ/genética , Antígenos de Histocompatibilidade Classe I/genética , Doadores não Relacionados , Alelos , Teste de Histocompatibilidade/métodos , Humanos , Transplante/métodosRESUMO
BACKGROUND: The association studies of killer cell immunoglobulin-like receptors (KIRs) with the occurrence of myelodysplastic syndromes (MDS) are limited worldwide; this study investigated the genetic risk/protective factors of MDS in KIR and human leucocyte antigen (HLA) systems to gain a better understanding of the role played by KIR and their cognate HLA ligands in MDS pathogenesis. METHODS: We genotyped a total number of 77 patients with MDS from Chinese Southern Han and 745 healthy controls for the KIR loci and HLA class I. The carrier frequencies of KIR genes, KIR genotypes, class I HLA ligands, and KIR-HLA combinations were calculated by direct counting. The effect of individual KIR genes and HLA ligands on MDS risk was evaluated by logistic regression analyses using SAS 9.2 software. RESULTS: We found that neither the KIR genes nor the KIR genotypes were associated with the occurrence of MDS. However, we observed that the frequencies for the strong inhibitory ligand HLA-Bw4 as well as KIR3DL1-HLA-Bw4 combination were significantly higher in healthy controls than those in the MDS patient group, respectively (73.42% vs. 62.34%, P = 0.038; 70.87% vs. 59.74%, P = 0.043). CONCLUSION: Our results showed that HLA-Bw4 ligand and KIR3DL1-HLA-Bw4 combination could confer a protective effect against MDS in Chinese Southern Han.