Background Mast cells can reshape the tumour immune microenvironment and greatly affect tumour occurrence and development. However, mast cell gene prognostic and predictive value in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study was conducted to identify and establish a prognostic mast cell gene signature (MCS) for assessing the prognosis and immunotherapy response of patients with HNSCC. Methods Mast cell marker genes in HNSCC were identified using single-cell RNA sequencing analysis. A dataset from The Cancer Genome Atlas was divided into a training cohort to construct the MCS model and a testing cohort to validate the model. Fluorescence in-situ hybridisation was used to evaluate the MCS model gene expression in tissue sections from patients with HNSCC who had been treated with programmed cell death-1 inhibitors and further validate the MCS. Results A prognostic MCS comprising nine genes (KIT, RAB32, CATSPER1, SMYD3, LINC00996, SOCS1, AP2M1, LAT, and HSP90B1) was generated by comprehensively analysing clinical features and 47 mast cell-related genes. The MCS effectively distinguished survival outcomes across the training, testing, and entire cohorts as an independent prognostic factor. Furthermore, we identified patients with favourable immune cell infiltration status and immunotherapy responses. Fluorescence in-situ hybridisation supported the MCS immunotherapy response of patients with HNSCC prediction, showing increased high-risk gene expression and reduced low-risk gene expression in immunotherapy-insensitive patients. Conclusions Our MCS provides insight into the roles of mast cells in HNSCC prognosis and may have applications as an immunotherapy response predictive indicator in patients with HNSCC and a reference for immunotherapy decision-making.

The tumor immune microenvironment plays an important role in head and neck squamous cell carcinoma (HNSCC). Reliable prognostic signatures able to accurately predict the immune landscape and survival rate of HNSCC patients are crucial to ensure an individualized/effective treatment. Here, we used HNSCC transcriptomic and clinical data retrieved from The Cancer Genome Atlas and identified differentially expressed immune-related long non-coding RNAs (DEirlncRNAs). DEirlncRNA pairs were recognized using univariate analysis. Cox and Lasso regression analyses were used to determine the association between DEirlncRNA pairs and the patients' overall survival and build the prediction model. Receiver operating characteristic curves and Kaplan-Meier survival curves were used to validate the prediction model. We then reevaluated the model based on the clinical factors, tumor-infiltrating immune cells, chemotherapeutic efficacy, and immunosuppression biomarkers. We built a risk score model based on 18 DEirlncRNA pairs, closely related to the overall survival of patients (hazard ratio: 1.376; 95% confidence interval: 1.302-1.453; P < 0.0001). Compared with two recently published lncRNA signatures, our DEirlncRNA pair signature had a higher area under the curve, indicating better prognostic performance. Additionally, the signature score positively correlated with aggressive HNSCC outcomes (low immunity score, significantly reduced CD8 + T cell infiltration, and low expression of immunosuppression biomarkers). However, high-risk patients might have high chemosensitivity. Overall, the lncRNAs signature established here shows promising clinical prediction and the effective disclosure of the tumor immune microenvironment in HNSCC patients; therefore, such signature might help distinguish patients that could benefit from immunotherapy.

Background: Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significance for targeted gene therapy and prognostic evaluation. PinX1, a tumor suppressor gene, was previously demonstrated to be a powerful tool for targeting telomerase in order to resist malignant tumor proliferation and migration. The aim of this study was to explore the mechanism through which PinX1 regulates epithelial-mesenchymal transition (EMT) and tumor metastasis in NPC and investigate its clinical significance and biological role with respect to disease progression.Methods: Cell Counting Kit-8 (CCK8), Transwell assays, Colony formation analysis and Xenograft tumorigenicity assay were used to measure the nasopharyngeal CD133 + cancer stem cell proliferation, migration, and invasion abilities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were conducted to investigate the underlying mechanism that PinX1 inhibits cell proliferation, migration, and invasion via regulating EMT in nasopharyngeal CD133 + CSCs. Results: We found that the overexpression of PinX1 and P53 inhibited cell proliferation, migration, and invasion, but that the inhibition of miR-200b blocked these effects, in nasopharyngeal CD133 + cancer stem cells (CSCs). Mechanistic investigations elucidated that PinX1 inhibits cell proliferation, migration, and invasion by regulating the P53/miR-200b-mediated transcriptional suppression of Snail1, Twist1, and Zeb1, consequently inhibiting EMT in nasopharyngeal CD133 + CSCs. Conclusions: Our findings indicate that PinX1 inhibits cell proliferation, migration, and invasion via P53/miR-200bregulated EMT in the malignant progression of human NPC, which might suggest novel clinical implications for disease treatment.

The 5‐year survival rate of laryngeal cancer continues to decline, and the laryngeal particularity of the anatomy adversely affects the patient's quality of life. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are closely correlated to key steps in the malignant progression of cancer cells. In this study, we report the role of lncRNA SBF2‐AS1/miR‐302b‐3p/TGFBR2 interactions in the metastasis of laryngeal squamous cell carcinoma (LSCC). We verified that SBF2‐AS1 was significantly downregulated in LSCC tissues and cell lines using qRT‐PCR analysis. Its low expression was correlated to lymph node metastasis and an advanced clinical stage. More importantly, LSCC patients with low expression of SBF2‐AS1 tended to have a poor prognosis. Based on this, we performed gain‐of‐function and loss‐of‐function experiments in LSCC cell lines. The results confirmed that knocking down SBF2‐AS1 can promote the metastasis of LSCC cells and enhance epithelial–mesenchymal transition phenotype, while the upregulation of SBF2‐AS1 expression resulted in the opposite. Our in vivo model verified that SBF2‐AS1 overexpression could inhibit LSCC cell metastasis. Subsequent mechanistic studies revealed that SBF2‐AS1 acted as a competing endogenous RNA that upregulated the expression of TGFBR2 by endogenous sponging for miR‐302b‐3p in LSCC cell lines. Moreover, miR‐302b‐3p overexpression reversed the inhibitory effects on LSCC metastasis induced by upregulation of SBF2‐AS1 expression, and inhibition of TGFBR2 expression reversed the effect of SBF2‐AS1 on metastasis. Our study proposes SBF2‐AS1 as a biomarker to predict the prognosis of LSCC patients and a novel potential therapeutic target.