Dickkopf-1 drives perineural invasion via PI3K-AKT signaling pathway in head and neck squamous cancer.

Perineural invasion (PNI) leads to the poor prognosis of head and neck squamous cancer (HNSCC) patients, but the mechanism of PNI remains unclear. Dickkopf-1 (DKK1), a secretory protein in the Wnt signaling pathway, was found indeed upregulated in HNSCC cells and tissues. Higher expression of DKK1 was statistically relevant to T stage, N stage, PNI, and poor prognosis of HNSCC. DKK1 overexpression enhanced the migration abilities of cancer cells. Moreover, DKK1-overexpressing cancer cells promoted cancer cells invasion of peripheral nerves in vitro and in vivo. Mechanistically, DKK1 could promote the PI3K-AKT signaling pathway. The migration abilities of neuroblastoma cells, which were enhanced by DKK1-overexpressing HNSCC cell lines, could be reversed by an inhibitor of Akt (MK2206). The association of DKK1 with PNI was also confirmed in HNSCC samples. Variables, including T stage, N stage, DKK1 expression, and PNI, were used to establish a nomogram to predict the survival probability and disease-free probability at 3 and 5 years. In summary, DKK1 can promote the PI3K-AKT signaling pathway in tumor cells and then could induce neuritogenesis and facilitate PNI. MK2206 may be a potential therapeutic target drug for HNSCC patients with PNI.

[Tislelizumab monotherapy for the treatment of recurrent/metastatic head and neck squamous cell carcinoma].

Objective:The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Methods:Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed. The information of sex, age, TNM stage, efficacy, and adverse reactions were collected. All patients were recruited from the RATIONALE 102 study. The primary end point was the objective response rate, and other end points included progression-free survival and overall survival. We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient, and used bioinformatics methods to enrich immune cells and analyze signaling pathways. All analyses were performed using R 4.1. 0 software, SPSS Statistics 24.0 software and GraphPad Prism 8. Results:As of May 31, 2020, the median follow-up time was 26.35 months. The objective response rate with tislelizumab was 50.0%, the median progression-free survival was 6.44 months, and the estimated median survival was 20.07 months. The incidence of grade 3 or higher adverse reactions was 66.7%, including hyponatremia, hypokalemia, hypercalcemia, etc. The expression of macrophage, Treg and neutrophil-related genes are higher in immune-sensitive patients, and the signaling pathways of the intestinal immune network for IgA production, graft versus host disease and autoimmune thyroid disease are significantly activated. Conclusion:Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma. The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.

Prognostic Significance of a Model Based on Acetaldehyde Dehydrogenase 2 Genetic Polymorphisms in Laryngeal Carcinoma.

OBJECTIVE: Because of the high costs associated with early-stage laryngeal carcinoma diagnosis and prognosis prediction, this study attempts to find valuable targets to establish a novel predictive model by focusing on the aldehyde dehydrogenase 2 (ALDH2) genotype and other peripheral blood markers. STUDY DESIGN: Retrospective study. SETTING: Tertiary comprehensive hospital. METHODS: From January 2011 to January 2021, 362 cases of laryngeal carcinoma were included and divided into 2 groups in this retrospective analysis. Information on medical history, alcohol, and tobacco consumption habits, ALDH2 genotypes, and other peripheral blood markers was collected. Endpoints of the current study included disease-free survival and overall survival. A nomogram model for overall survival was established and evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 236 patients were included in the training cohort, and the other 126 were included in the validation cohort. The median follow-up of the patients was 9.6 years (interquartile range: 7.5-12.5 years). Peripheral fibrinogen, hemoglobin, and ALDH2 genotypes were significantly associated with an increase in laryngeal carcinoma mortality rate on Kaplan-Meier curves. The ROC curve showed that the effectiveness of overall survival prediction by the nomogram model was better than that of traditional clinical staging. CONCLUSION: A prognostic nomogram of laryngeal carcinoma patients involving ALDH2 and peripheral blood markers and T and N stages was constructed and validated.

Near complete response to a pembrolizumab-based therapeutic strategy in an abdominal metastatic head and neck squamous cell carcinoma case.

Metastasis of head and neck squamous cell carcinoma rarely occurs in hepatic cancer and has a poor prognosis (median survival of 4 months). The efficacy of immunotherapy for these patients remains unknown. Herein, we present a patient with hypopharyngeal carcinoma metastasis to the liver with TERT and TP53 mutations together with a combined positive score of 70. The tumor invaded the abdominal wall, liver, inferior vena cava and retroperitoneal lymph nodes. The patient was treated with pembrolizumab combined with cisplatin and 5-FU for four cycles and has been maintained on pembrolizumab monotherapy until now. The patient achieved a near complete response of hepatic and subcutaneous metastases, and the tumor thrombus disappeared completely. The patient developed grade I rashes on the trunk, which were considered immune-related adverse events; thus, the patient presented a significant tumor response and good tolerance to the therapeutic strategy. On the basis of this observation, pembrolizumab-based therapeutic strategies may be an effective alternative for metastatic hypopharyngeal carcinoma and may prolong overall survival and progression-free survival, which should be confirmed by more patients in the future. Immune-related adverse events also need attention.