RESUMO
Lung adenocarcinoma (LUAD) is a malignant tumor with high lethality, and the aim of this study was to identify promising biomarkers for LUAD. Using the TCGA-LUAD dataset as a discovery cohort, a novel joint framework VAEjMLP based on variational autoencoder (VAE) and multilayer perceptron (MLP) was proposed. And the Shapley Additive Explanations (SHAP) method was introduced to evaluate the contribution of feature genes to the classification decision, which helped us to develop a biologically meaningful biomarker potential scoring algorithm. Nineteen potential biomarkers for LUAD were identified, which were involved in the regulation of immune and metabolic functions in LUAD. A prognostic risk model for LUAD was constructed by the biomarkers HLA-DRB1, SCGB1A1, and HLA-DRB5 screened by Cox regression analysis, dividing the patients into high-risk and low-risk groups. The prognostic risk model was validated with external datasets. The low-risk group was characterized by enrichment of immune pathways and higher immune infiltration compared to the high-risk group. While, the high-risk group was accompanied by an increase in metabolic pathway activity. There were significant differences between the high- and low-risk groups in metabolic reprogramming of aerobic glycolysis, amino acids, and lipids, as well as in angiogenic activity, epithelial-mesenchymal transition, tumorigenic cytokines, and inflammatory response. Furthermore, high-risk patients were more sensitive to Afatinib, Gefitinib, and Gemcitabine as predicted by the pRRophetic algorithm. This study provides prognostic signatures capable of revealing the immune and metabolic landscapes for LUAD, and may shed light on the identification of other cancer biomarkers.
Assuntos
Adenocarcinoma de Pulmão , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Prognóstico , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/genéticaRESUMO
BACKGROUND: The purpose of this study was to detect the serum microRNAs (miRNAs) that are differentially expressed in cervical squamous cell carcinoma (SCC) patients and negative controls, with a focus on the miRNA profiles of the patients before and after surgery. The aim of the study is to evaluate the potential of these miRNAs as novel markers for the post-therapeutic monitoring of cervical SCC patients. RESULTS: A total of 765 serum miRNAs from 10 cervical SCC patients before surgery, 10 cervical SCC patients after surgery, and 10 negative controls were profiled using a TaqMan MicroRNA Array. A set of selected differentially expressed miRNAs were further analyzed in the patients at different perioperative periods, including preoperative, 1 week postoperative, and one month postoperative. The results showed that several serum miRNAs were differentially expressed in the cervical SCC patients compared with the negative controls, including miR-646, miR-141* and miR-542-3p. More importantly, we found that levels of specific serum miRNAs were deregulated in the pre- and postoperative stages, and these miRNAs could be useful for post-therapeutic monitoring of disease progression. Finally, we depicted a regulatory network of differentially expressed serum miRNAs, and many possible target genes were predicted in the estrogen-mediated signal pathways, supporting the hypothesis that cervical SCC is a hormone-associated gynecological disease. CONCLUSIONS: Our study demonstrated that the circulating miRNAs miR-646, miR-141* and miR-542-3p could potentially serve as non-invasive biomarkers for cervical SCC. The levels of these specific miRNAs might be useful for the post-therapeutic monitoring of disease progression. This is the first report showing that circulating miRNAs could serve as biomarkers for the therapeutic intervention of cervical SCC.
Assuntos
Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/cirurgia , Análise por Conglomerados , Feminino , Redes Reguladoras de Genes/genética , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Avaliação de Resultados em Cuidados de Saúde/métodos , Período Pós-Operatório , Período Pré-Operatório , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/cirurgiaRESUMO
OBJECTIVE: To establish a detecting method of Salmonella, Shigella and Staphylococcus aureus by using quantum dots and immunomagnetic beads. METHODS: The polychrome colour CdSe quantum dots were synthetized by water phase process. Triad colour quantum dots were conjugated with specific anti-Salmonella, anti-Shigella and anti-Staphylococcus aureus antibody by covalent cross-linking reaction, and then the coupled product was confirmed by SDS-PAGE and ultraviolet absorption spectrum. Using immunomagnetic enrichment and quantum dots labeling specific antibody, the fluorescence intensity of Salmonella, Shigella and Staphylococcus aureus were observed by fluorescence microscope. RESULTS: The coupled reaction was successful by SDS-PAGE and ultraviolet absorption spectrum. Using immunomagnetic enrichment and quantum dots with different color and different wavelength labeling specific antibody, the detection time was less than 2h in the same reaction system. The samples infection with target bacteria were detected directly. The detection limit was 10 CFU/ml. CONCLUSION: This method can detect Salmonella, Shigella and Staphylococcus aureus quickly and specificly.
