RESUMEN
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis. Cancer-associated fibroblasts (CAFs) play a critical role in regulating TNBC tumor development. This study aimed to identify and characterize a specific subtype of CAFs associated with TNBC. Initially, using high-throughput bulk transcriptomic data in two cohorts, we identified three CAF-related subtypes (CS1, CS2, CS3) in TNBC samples. These three CAFs subtypes were closely linked to the tumor microenvironment. The CS1 subtype exhibited a relatively immune-rich microenvironment and a favourable prognosis, whereas the CS3 subtype displayed an immune-deprived tumor microenvironment and an unfavourable prognosis. Through WGCNA analysis, POSTN was identified as a key biomarker for CAFs associated with TNBC. Then, POSTN+CAFs was identified and characterized. Both POSTN and POSTN+CAFs showed significant positive correlations with stromal molecules HGF and MET at both the transcriptional and protein levels. Specifically co-localized with CAFs in the tumor stromal area, POSTN, produced by POSTN+CAFs, could modulate the HGF-MET axis, serving as a bypass activation pathway to regulate tumor cell proliferation in response to EGFR inhibitor and MET inhibitor. This study underscores the significance of POSTN and POSTN+CAFs as crucial targets for the diagnosis and treatment of TNBC.
Asunto(s)
Fibroblastos Asociados al Cáncer , Moléculas de Adhesión Celular , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas c-met , Neoplasias de la Mama Triple Negativas , Microambiente Tumoral , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Femenino , Proteínas Proto-Oncogénicas c-met/metabolismo , Proteínas Proto-Oncogénicas c-met/genética , Factor de Crecimiento de Hepatocito/metabolismo , Factor de Crecimiento de Hepatocito/genética , Proliferación Celular , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , PronósticoRESUMEN
BACKGROUND: Postoperative radiotherapy (PORT) is commonly used to treat patients with resected stage III non-small cell lung cancer (NSCLC), but its effectiveness remains uncertain. This retrospective cohort study aimed to investigate the impact of PORT on overall survival (OS) and evaluate its heterogeneity among subgroups of patients. METHODS: A total of 6305 patients with resected stage III NSCLC were included in this study from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching was conducted to balance baseline characteristics between the patients who received PORT and those who did not. OS was used as the primary outcome. Subgroup analysis was performed to identify which patient subgroups might benefit more from PORT. RESULTS: Overall, no significant difference was observed in OS between the 2 groups with or without propensity score matching. However, subgroup analysis demonstrated that PORT improved OS in patients with certain characteristics, including stage IIIA/N2, stage IIIB, squamous cell carcinoma, tumor grade III-IV, or lymph node ratio (LNR)â >â 1/3. Multivariate analysis showed that several variables were associated with adverse prognostic factors for OS, such as marital status (others), race (white), male gender, squamous cell carcinoma, elderly age, advanced stage, poor histological differentiation grade, high LNR, and not receiving chemotherapy. CONCLUSION: In patients with resected stage III NSCLC, PORT may not be beneficial for all patients. However, it may improve survival time in certain patient subgroups, such as those with stage IIIA/N2, stage IIIB, squamous cell carcinoma, tumor grade III to IV, or LNRâ >â 1/3. These findings provide important information for clinical decision-making and future research regarding the use of PORT in patients with resected stage III NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Masculino , Anciano , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Radioterapia Adyuvante , Estadificación de Neoplasias , Carcinoma de Células Escamosas/patologíaRESUMEN
Background: Lung adenocarcinoma, as a common histological type in lung cancer, the overall survival is very low, and the prognosis is poor because it is difficult to find and easily recurs. Therefore, this study aimed to explore the role of the secreted protein beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) in the development of lung adenocarcinoma and to evaluate its potential significance for early clinical biomarker screening. Methods: The mRNA expression profiles of patients with lung adenocarcinoma and normal controls were analyzed via The Cancer Genome Atlas (TCGA) database. Serum samples of clinical lung cancer patients and healthy people were obtained, and the differences in B3GNT3 expression in different stages of lung adenocarcinoma and in healthy tissues were compared. Kaplan-Meier (K-M) curves were drawn to clarify the influence of high and low expression of B3GNT3 on the prognosis of patients. Peripheral blood samples from patients with lung adenocarcinoma and healthy people were obtained clinically, and receiver operating characteristic (ROC) curves were drawn to clarify the sensitivity and specificity of B3GNT3 expression for the diagnosis of lung adenocarcinoma. Lung adenocarcinoma cells were cultured in vitro, the expression of B3GNT3 was knocked down by lentivirus infection. The expression of the apoptosis-associated genes was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results: The secreted protein B3GNT3 is significantly differentially expressed in the serum of patients with lung adenocarcinoma versus normal controls. Subgroup analysis according to lung adenocarcinoma clinical stage showed that the higher the clinical stage of lung adenocarcinoma was, the higher the B3GNT3 expression. Enzyme-linked immunosorbent assay (ELISA) revealed that B3GNT3 expression was significantly increased in the serum of patients with lung adenocarcinoma and significantly decreased after surgery. By inhibiting programmed cell death-ligand 1 (PD-L1), the level of apoptosis was significantly increased and the proliferative capacity was significantly inhibited. In contrast, the level of apoptosis was significantly increased and the proliferation ability was significantly inhibited after simultaneous overexpression of B3GNT3 and inhibition of PD-L1. Conclusions: High expression of the secreted protein B3GNT3 in lung adenocarcinoma is closely related to prognosis and can serve as a potential biological marker for the early screening of lung adenocarcinoma.
RESUMEN
Neuronal nuclear inclusion disease (NIID) is a rare and chronic progressive neurological degenerative disease. We presented a 68-year-old man with paroxysmal orientation disorder 1 year prior, mental and behavioral disorders for 2 days, and confirmed the diagnosis of NIID with skin biopsy. We suggest that patients with atypical clinical symptoms showed characteristic high signal in the dermatomedullary junction on DWI; NIID should be considered.
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There are limited reports with respect to the study on the epithelium-mesenchymal transformation (EMT) mediated by Snail in the ovarian cancer. This study detected the expression of Snail and related EMT markers in the ovarian cancer tissues, and explored the possible molecular mechanism of EMT mediated by Snail in the metastasis of ovarian cancer. The patients diagnosed with ovarian cancer according to the pathology were recruited in this study during 2010-2014. The carcinoma tissue and normal tissue adjacent to carcinoma were surgically obtained from patients. The genes of E-cadherin, ß-catenin, Fibronectin and N-cadherin were detected using the RT-PCR. The 64 patients were recruited and diagnosed as ovarian cancer by pathological examination. The expression levels of Snail, Fibronectin and N-cadherin in the stage III and IV were higher than those in the stage I and II, respectively (all P < 0.05). However, the expression levels of E-cadherin and ß-catenin decreased along with the stage developed (trend test, both P < 0.05), respectively. The expression of Snail was positively correlated with the expression of Fibronectin, N-cadherin, but negatively correlated with the expression of E-cadherin and ß-catenin. The number of A2780 cells entering into the lower compartment in the group of carcinoma tissue were significantly higher than that in the group of normal tissue after transfected with Snail expression vector. While, the invasion ability of A2780 significantly reduced after RNAi-Snail. The correlation between Snail and invasion and metastasis of ovarian cancer and epithelial-mesenchymal transition based on tissue and cell levels, and to some extent explored the molecular mechanism of the EMT process mediated by Snail.