RESUMEN
Head and neck squamous carcinoma (HNSC) is a prevalent malignant disease, with the majority of patients being diagnosed at an advanced stage. Endoplasmic reticulum stress (ERS) is considered to be a process that promotes tumorigenesis and impacts the tumor microenvironment (TME) in various cancers. The study aims to investigate the predictive value of ERS in HNSC and explore the correlation between ERS-related genes and TME. A series of bioinformatics analyses were carried out based on mRNA and scRNA-seq data from the TCGA and GEO databases. We conducted RT-qPCR and western blot to validate the signature, and performed cell functional experiments to investigate the in vitro biological functions of the gene. We identified 63 ERS-related genes that were associated with outcome and stage in HNSC. A three-gene signature (ATF6, TRIB3, and UBXN6) was developed, which presents predictive value in the prognosis and immunotherapy response of HNSC patients. The high-risk group exhibited a worse prognosis but may benefit from immunotherapy. Furthermore, there was a significant correlation between the signature and immune infiltration. In the high-risk group, fibroblasts were more active in intercellular communication, and more T cells were observed at the end of the sequential phase. The genes in the ERS-related signature were overexpressed in HNSC cells, and the knockdown of TRIB3 significantly inhibited cell proliferation and migration. This study established a novel ERS-related signature that has potential implications for HNSC therapy and the understanding of TME.
Asunto(s)
Estrés del Retículo Endoplásmico , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral , Humanos , Estrés del Retículo Endoplásmico/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Microambiente Tumoral/genética , Pronóstico , Línea Celular Tumoral , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Factor de Transcripción Activador 6/metabolismo , Factor de Transcripción Activador 6/genética , Femenino , Proliferación Celular/genética , Biología Computacional/métodos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Masculino , Movimiento Celular/genética , Perfilación de la Expresión Génica , Transcriptoma , Proteínas Represoras , Proteínas de Ciclo CelularRESUMEN
BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 months). Publication bias was assessed using Begg's test and Egger's test. RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery [total thyroidectomy (TT) vs. lobectomy], surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT, while preoperative PTH was a protective factor. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.
Asunto(s)
Hipoparatiroidismo , Complicaciones Posoperatorias , Tiroidectomía , Humanos , Hipoparatiroidismo/etiología , Hipoparatiroidismo/epidemiología , Tiroidectomía/efectos adversos , Factores de Riesgo , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Femenino , Masculino , Factores SexualesRESUMEN
Gliomas are the major type of primary brain tumors. Accumulating research has demonstrated that tubulin is connected with the development and malignant progression of tumors. TUBA1C is a subtype of α-tubulin and is linked to prognosis in multiple cancers. In this study, the prognosis-related gene TUBA1C in glioma was identified and analyzed by bioinformatic approaches such as Kaplan-Meier (KM) survival time analysis, univariate and multivariate Cox analysis, receiver operating characteristic (ROC) analysis and functional enrichment analysis. Based on the above analyses, we found that glioma tissues had significantly higher expression of TUBA1C than normal brain tissues, and high expression of TUBA1C has worse prognosis in glioma. Gene set enrichment analysis (GSEA) revealed the signaling pathways related to the cell cycle. Furthermore, knockdown of TUBA1C also inhibited proliferation and migration and caused apoptosis and G2/M phase arrest in glioma cells. This study demonstrated that high TUBA1C expression correlated with poor outcomes in glioma patients and that knocking down TUBA1C suppressed glioma cell proliferation via cell cycle arrest. In addition, TUBA1C might be a therapeutic biomarker for gliomas.