ABSTRACT
AIMS: Cancer-associated fibroblasts (CAFs) have been shown to promote the metastasis of head and neck squamous cell carcinoma (HNSCC), but the underlying mechanisms remain unclear. The purpose of this study is to identify gene in CAFs that are associated with metastasis and to preliminarily validate its impact on the metastasis of HNSCC. MATERIALS AND METHODS: Scissor analysis was utilized to process single-cell and bulk RNA sequencing datasets, identifying genes associated with the metastasis of HNSCC through differential gene expression analysis. A risk model was constructed using LASSO regression analysis. Quantitative real time-PCR and Western blot were employed to measure mRNA and protein expressions, respectively. Multiplex immunohistochemistry (mIHC) was used to assess protein expression in CAFs. siRNA was utilized to achieve gene knockdown. CCK-8 and Transwell assays were employed to evaluate the biological characteristics of HNSCC cells. KEY FINDINGS: Compare to the nonmetastatic primary CAFs (nmCAFs), tissue inhibitors of metalloproteinase-1 (TIMP1) was founded to be overexpressed in the cells and tissues of metastatic primary CAFs (mCAFs). Knocking down TIMP1 in CAFs can signifucantly inhibit the proliferation, invasion, and migration of HNSCC cells. SIGNIFICANCE: CAFs facilitate HNSCC cell metastasis by upregulating TIMP1, highlighting TIMP1 as a potential therapeutic target in HNSCC metastasis management.
Subject(s)
Cancer-Associated Fibroblasts , Head and Neck Neoplasms , Single-Cell Analysis , Squamous Cell Carcinoma of Head and Neck , Tissue Inhibitor of Metalloproteinase-1 , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/secondary , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/metabolism , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-1/genetics , Single-Cell Analysis/methods , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Neoplasm Metastasis/genetics , Cell Movement/genetics , Sequence Analysis, RNA/methods , Male , FemaleABSTRACT
OBJECTIVES: Current scales for Pemphigus vulgaris (PV) do not adequately represent the clinical variability of oral lesions. This study aimed to develop an independent scale, the Pemphigus Oral Lesions Area Index (POLAI), for assessment of oral PV exclusively, and compare POLAI, Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Oral Disease Severity Score (ODSS) regarding inter- and intra-observer reliability and validity. MATERIALS AND METHODS: Retrospective cohort included 209 sets of digital-photographs. Additional clinical cohort included 32 PV patients. All visits were assessed by four clinicians using the PDAI, ABSIS, ODSS and POLAI, and were rated by three specialists using the Physician's Global Assessment (PGA). RESULTS: The intraclass correlation coefficient showed the inter-observer reliability with 0.89 and 0.86 for PDAI, 0.87 for ABSIS, 0.93 for ODSS, 0.96 for POLAI, and 0.97 and 0.96 for PGA. Intra-observer agreements showed excellent reliability for all 4 scores. Highest correlation was observed between PGA and POLAI (correlation coefficients were 0.96). The mean time taken to complete each scale was within 1.5 min. CONCLUSION: POLAI is valid for the assessment of oral PV with superior inter- and intra-observer reliability to PDAI, ABSIS and ODSS, and is feasible in clinic.
ABSTRACT
Background: The purpose of this study was to identify the prognostic value of cuproptosis and copper metabolism-related genes, to clarify their molecular and immunological characteristics, and to elucidate their benefits in head and neck squamous cell carcinoma (HNSCC). Methods: The details of human cuproptosis and copper metabolism-related genes were searched and filtered from the msigdb database and the latest literature. To identify prognostic genes associated with cuproptosis and copper metabolism, we used least absolute shrinkage and selection operator regression, and this coefficient was used to set up a prognostic risk score model. HNSCC samples were divided into two groups according to the median risk. Afterwards, the function and immune characteristics of these genes in HNSCC were analyzed. Results: The 14-gene signature was constructed to classify HNSCC patients into low-risk and high-risk groups according to the risk level. In the The Cancer Genome Atlas (TCGA) cohort, the overall survival (OS) rate of the high-risk group was lower than that of the low-risk group (P < 0.0001). The area under the curve of the time-dependent Receiver Operator Characteristic (ROC) curve assessed the good performance of the genetic signature in predicting OS and showed similar performance in the external validation cohort. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment assays and Protein-Protein Interaction (PPI) protein networks have been used to explore signaling pathways and potential mechanisms that were markedly active in patients with HNSCC. Furthermore, the 14 cuproptosis and copper metabolism-related genes were significantly correlated with the immune microenvironment, suggesting that these genes may be linked with the immune regulation and development of HNSCC. Conclusions: Our results emphasize the significance of cuproptosis and copper metabolism as a predictive biomarker for HNSCC, and its expression levels seem to be correlated with immune- related features; thus, they may be a possible biomarker for HNSCC prognosis.
