RESUMEN
Ferroptosis and cuproptosis are recently discovered forms of cell death that have gained interest as potential cancer treatments, particularly for hepatocellular carcinoma. Long non-coding RNAs (lncRNAs) influence cancer cell activity by interacting with various nucleic acids and proteins. However, the role of ferroptosis and cuproptosis-related lncRNAs (FCRLs) in cancer remains underexplored. Ferroptosis and cuproptosis scores for each sample were assessed using Gene Set Variation Analysis (GSVA). Weighted correlation network analysis identified the FCRLs most relevant to our study. A risk model based on FCRLs was developed to categorize patients into high-risk and low-risk groups. We then compared overall survival (OS), tumor immune microenvironment, and clinical characteristics between these groups. The IPS score and ImmuCellAI webpage were used to predict the association between FCRL-related signatures and immunotherapy response. Finally, we validated the accuracy of FCRLs in hepatocellular carcinoma cell lines using induction agents (elesclomol and erastin). Patients in different risk subgroups showed significant differences in OS, immune cell infiltration, pathway activity, and clinical characteristics. Cellular assays revealed significant changes in the expression of AC019080.5, AC145207.5, MIR210HG, and LINC01063 in HCC cell lines following the addition of ferroptosis and cuproptosis inducers. We created a signature of four FCRLs that accurately predicted survival in HCC patients, laid the foundation for basic research related to ferroptosis and cuproptosis in hepatocellular carcinoma, and provided therapeutic recommendations for HCC patients.
Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Ferroptosis/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , ARN Largo no Codificante/genética , Pronóstico , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Microambiente Tumoral/genética , Masculino , Femenino , Biomarcadores de Tumor/genética , Persona de Mediana EdadRESUMEN
PURPOSE: To explore the optimal treatment strategy and relevant prognostic analysis for hypopharyngeal squamous-cell carcinoma patients (HSCC) with T3-T4 or node-positive. METHODS AND MATERIALS: From 2004 to 2018, data for 2574 patients from the Surveillance, Epidemiology, and End Results database (SEER) and 66 patients treated at our center from 2013 to 2022 with T3-T4 or N + HSCC were collected. Patients in the SEER cohort were randomly assigned to the training set or validation set at a 7:3 ratio. Variables with statistically significant (P < 0.05) in univariate COX regression analysis or clinical significance were included in the multivariate COX regression model and subsequently used to construct the nomogram. RESULTS: The 3-year OS (52.9%vs44.4%, P < 0.01) and 3-year CSS rate (58.7%vs51.5%, P < 0.01) rates in the surgery combined with postoperative adjuvant therapy (S + ADT) group were superior to the radiotherapy combined with chemotherapy (CRT) group. The multivariate Cox regression analysis of the training group showed that age, race, marital status, primary site, T stage, N stage, and treatment modalities were correlated with OS and CSS. Based on those variables, we constructed nomograms for OS and CSS. Both the internal and external validation showed high prediction accuracy of the nomogram. CONCLUSION: Among patients with T3-T4 or node-positive, S + ADT was associated with superior OS and CSS compared to those treated with primary CRT, while the survival rate in the CRT group was comparable to S + ADT group in T2-T3 disease. The internal and external verification shows that the prognostic model has good discrimination ability and accuracy.