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1.
Cancer Biol Ther ; 25(1): 2355705, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38778753

RESUMO

Triple-negative breast Cancer (TNBC) is an aggressive subtype lacking estrogen, progesterone, and HER2 receptors. Known for limited targeted therapies, it poses challenges and requires personalized treatment strategies. Differential analysis revealed a significant decrease in keratin 81 (KRT81) expression in non-TNBC samples and an increase in TNBC samples, lower KRT81 expression correlated with better TNBC patient outcomes. It emerged as an independent predictive factor for TNBC, with associations found between its expression and clinically relevant features. We further developed a nomogram for survival probability assessment based on Cox regression results, demonstrating its accuracy through calibration curves. Gene annotation analysis indicated that KRT81 is involved in immune-related pathways and tumor cell adhesion. KRT81 is associated with immune cell infiltration of Follicular helper T cells (Tfh) and CD8 + T cells, suggesting its potential impact on the immunological microenvironment. The study delved into KRT81's predictive value for immunotherapy responses, high expression of KRT81 was associated with greater potential for immune evasion. Single-cell RNA sequencing analysis pinpointed KRT81 expression within a specific malignant subtype which was a risk factor for TNBC. Furthermore, KRT81 promoted TNBC cell proliferation, migration, invasion, and adhesion was confirmed by gene knockout or overexpression assay. Co-culture experiments further indicated KRT81's potential role in inhibiting CD8 + T cells, and correlation analysis implied KRT81 was highly correlated with immune checkpoint CD276, providing insights into its involvement in the immune microenvironment via CD276. In conclusion, this comprehensive study positions KRT81 as a promising prognostic marker for predicting tumor progression and immunotherapy responses in TNBC.


Assuntos
Biomarcadores Tumorais , Linfócitos T CD8-Positivos , Imunoterapia , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Prognóstico , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/imunologia
2.
Front Med (Lausanne) ; 9: 969225, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186815

RESUMO

Purpose: Biliary drainage is an important modality for extrahepatic obstructive jaundice both in patients with palliative and resectable. Currently, endoscopic biliary drainage is preferred in clinical practice, including endoscopic nasobiliary drainage (ENBD) and endoscopic biliary stenting (EBS), both of which have their own advantages and disadvantages. The purpose of our study was to compare the safety and efficacy of endoscopic biliary stenting (EBS) only vs. EBS plus nasobiliary drain for obstructive jaundice. Methods: We consecutively reviewed patients with endoscopic biliary drainage in our institution from November 2014 to March 2021. Combined (ENBD plus stent) and single approach (EBS only) were defined as combined approach and single modality, respectively, and all eligible patients were divided into a combined approach group and a single modality group. We compared combined vs. single modality approaches to investigate whether there were statistical differences in liver chemistries, postoperative adverse events, and stent patency time. Results: In 271 patients, a total of 356 times endoscopic biliary drainages were performed. All eligible patients were divided into the combined approach group (n = 74) and the single modality group (n = 271). The combined approach was associated with a lower incidence of postoperative cholangitis and bleeding and greater improvement in liver chemistries, although it was not statistically significant. However, it was superior to the single modality group in terms of hospital stay (12.7 ± 5.2 vs. 14.5 ± 7.9 days, p = 0.020 < 0.05) and stent patency time (8.1 ± 3.9 vs. 4.3±2.7 months, p = 0.001 < 0.05). Conclusion: Endoscopic combined (ENBD plus stent) drainage is a more advantageous biliary drainage method that is characterized by more adequate biliary drainage, a lower incidence of postoperative adverse events, and longer effective biliary drainage time.

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