RESUMO
Breast cancer (BC) continues to pose a significant burden on global cancer-related morbidity and mortality, primarily driven by metastasis. However, the combined influence of microRNAs (miRNAs) and intratumoral microbiota on BC metastasis remains largely unexplored. In this study, we aimed to elucidate the interplay between intratumoral microbiota composition, miRNA expression profiles, and their collective influence on metastasis development in BC patients by employing 16S rRNA sequencing and qPCR methodologies. Our findings revealed an increase in the expression of miR-149-5p, miR-20b-5p, and miR-342-5p in metastatic breast cancer (Met-BC) patients. The Met-BC patients exhibited heightened microbial richness and diversity, primarily attributed to diverse pathogenic bacteria. Taxonomic analysis identified several pathogenic and pro-inflammatory species enriched in Met-BC, contrasting with non-metastatic breast cancer (NonMet-BC) patients, which displayed an enrichment in potential probiotic and anti-inflammatory species. Notably, we identified and verified a baseline prognostic signature for metastasis in BC patients, with its clinical relevance further validated by its impact on overall survival. In conclusion, the observed disparities in miRNA expression and species-level bacterial abundance suggest their involvement in BC progression. The development of a prognostic signature holds promise for metastasis risk assessment, paving the way for personalized interventions and improved clinical outcomes in BC patients.
Assuntos
Neoplasias da Mama , Progressão da Doença , MicroRNAs , Microbiota , Metástase Neoplásica , Humanos , MicroRNAs/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/microbiologia , Feminino , Microbiota/genética , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Regulação Neoplásica da Expressão Gênica , Prognóstico , Adulto , IdosoRESUMO
Early breast cancer patients often experience relapse due to residual disease after treatment. Liquid biopsy is a methodology capable of detecting tumor components in blood, but low concentrations at early stages pose challenges. To detect them, next-generation sequencing has promise but entails complex processes. Exploring larger blood volumes could overcome detection limitations. Herein, a total of 282 high-volume plasma and blood-cell samples were collected for dual ctDNA/CTCs detection using a single droplet-digital PCR assay per patient. ctDNA and/or CTCs were detected in 100% of pre-treatment samples. On the other hand, post-treatment positive samples exhibited a minimum variant allele frequency of 0.003% for ctDNA and minimum cell number of 0.069 CTCs/mL of blood, surpassing previous investigations. Accurate prediction of residual disease before surgery was achieved in patients without a complete pathological response. A model utilizing ctDNA dynamics achieved an area under the ROC curve of 0.92 for predicting response. We detected disease recurrence in blood in the three patients who experienced a relapse, anticipating clinical relapse by 34.61, 9.10, and 7.59 months. This methodology provides an easily implemented alternative for ultrasensitive residual disease detection in early breast cancer patients.
RESUMO
No disponible
Assuntos
Humanos , Feminino , Idoso , Cálculos/complicações , Cálculos/diagnóstico por imagem , Duodenopatias/complicações , Duodenopatias/diagnóstico por imagem , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologiaAssuntos
Obstrução Duodenal/etiologia , Cálculos Biliares/complicações , Obstrução da Saída Gástrica/etiologia , Dor Abdominal/etiologia , Idoso , Duodenopatias/fisiopatologia , Feminino , Cálculos Biliares/cirurgia , Obstrução da Saída Gástrica/diagnóstico , Humanos , Radiografia Abdominal/métodos , Vômito/etiologiaAssuntos
Fraturas da Coluna Vertebral/etiologia , Espondilite Anquilosante/complicações , Vértebras Torácicas/lesões , Tomografia Computadorizada por Raios X , Acidentes por Quedas , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/lesões , Masculino , Pessoa de Meia-Idade , Marca-Passo Artificial , Paraplegia/etiologia , Compressão da Medula Espinal/etiologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Espondilite Anquilosante/diagnóstico , Espondilolistese/diagnóstico por imagem , Espondilolistese/etiologia , Síncope/complicações , Vértebras Torácicas/diagnóstico por imagemRESUMO
No disponible