RESUMO
BACKGROUND: Advanced cervical cancer carries a particularly poor prognosis, and few treatment options exist. Identification of effective molecular markers is vital to improve the individualisation of treatment. We investigated transcriptional data from cervical carcinomas related to patient survival and recurrence to identify potential molecular drivers for aggressive disease. METHODS: Primary tumour RNA-sequencing profiles from 20 patients with recurrence and 53 patients with cured disease were compared. Protein levels and prognostic impact for selected markers were identified by immunohistochemistry in a population-based patient cohort. RESULTS: Comparison of tumours relative to recurrence status revealed 121 differentially expressed genes. From this gene set, a 10-gene signature with high prognostic significance (p = 0.001) was identified and validated in an independent patient cohort (p = 0.004). Protein levels of two signature genes, HLA-DQB1 (n = 389) and LIMCH1 (LIM and calponin homology domain 1) (n = 410), were independent predictors of survival (hazard ratio 2.50, p = 0.007 for HLA-DQB1 and 3.19, p = 0.007 for LIMCH1) when adjusting for established prognostic markers. HLA-DQB1 protein expression associated with programmed death ligand 1 positivity (p < 0.001). In gene set enrichment analyses, HLA-DQB1high tumours associated with immune activation and response to interferon-γ (IFN-γ). CONCLUSIONS: This study revealed a 10-gene signature with high prognostic power in cervical cancer. HLA-DQB1 and LIMCH1 are potential biomarkers guiding cervical cancer treatment.
Assuntos
Cadeias beta de HLA-DQ/genética , Proteínas com Domínio LIM/genética , Transcriptoma , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Cadeias beta de HLA-DQ/fisiologia , Humanos , Proteínas com Domínio LIM/fisiologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Análise de Sobrevida , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVES: The purpose of this study was to identify differentially expressed genes (DEGs) related to acute lung injury (ALI) induced by sepsis with DNA microarray. MATERIALS AND METHODS: Gene expression profile GSE10474 was downloaded from Gene Expression Omnibus (GEO) database which includes 34 samples, among which 13 patients with ALI + sepsis and 21 patients with sepsis alone. The DEGs were identified between ALI + sepsis and sepsis alone samples using R, which were further analyzed using bioinformatics methods. Firstly, HitPredict was used to search protein-protein interactions of the DEGs. Secondly, WebGestalt was adopted for functional enrichment analysis of genes in the interaction networks. Finally, DNA methylation was analyzed to explain the differential expression. RESULTS: A total of 12 genes were identified as DEGs by comparing chip data from ALI + sepsis samples and those from sepsis alone samples, among which occludin (OCLN) and major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1) had 21 and 6 interactors, respectively. Functional enrichment analysis revealed several significantly over-represented terms: cellular component organization, macromolecular organization and biosynthesis, and response to stimulus. In addition, methylation was found in the promoters of OCLN and HLA-DQB1. CONCLUSIONS: We screened DEGs in septic ALI samples, and several interesting genes were obtained, especially OCLN and HLA-DQB1. They may be developed into marker genes for diagnosis or treatment of ALI.
Assuntos
Lesão Pulmonar Aguda/genética , Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Metilação de DNA , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/fisiologia , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/fisiologia , Humanos , Ocludina/genética , Ocludina/fisiologia , Sepse/genéticaRESUMO
Human leucocyte antigen (HLA) DQB1*0602 allele, a well-known genetic risk factor for narcolepsy, has been associated with sleep parameters in healthy subjects. We aimed to assess the association of this allele with daytime sleepiness and altered sleep electroencephalogram characteristics in the general population and in patients with obstructive sleep apnoea syndrome (OSAS). Eight hundred and ninety-four individuals from the Epidemiologic Study of Sleep were genotyped for the HLA DQB1*0602 allele. Full-night polysomnography was performed, and daytime sleepiness was analysed according to the Epworth Sleepiness Scale. HLA-DQB1*0602 allele-positive and -negative subjects in the general population, as well as in patients with OSAS, exhibited similar sleep parameters and levels of daytime sleepiness. However, spectral analysis showed that allele-positive individuals with OSAS exhibited higher theta power during sleep Stage 1 (P < 0.05) in occipital derivations, and lower delta power during sleep Stages 1 and 2 (P < 0.01) compared with individuals negative for the allele, even after correction for potential confounders as age, sex, body mass index and European ancestry. No significant differences in the electroencephalogram variables were found in individuals without OSAS. The data highlight the HLA-DQB1*0602 as a potential genetic factor influencing sleep physiology in individuals diagnosed with OSAS.