Molecular Subtypes Based on Cell Differentiation Trajectories in Head and Neck Squamous Cell Carcinoma: Differential Prognosis and Immunotherapeutic Responses.

Objective: Head and neck squamous cell carcinoma (HNSCC) is one of the most common and lethal malignant tumors. We aimed to investigate the HNSCC cell differentiation trajectories and the corresponding clinical relevance. Methods: Based on HNSCC cell differentiation-related genes (HDRGs) identified by single-cell sequencing analysis, the molecular subtypes and corresponding immunity, metabolism, and stemness characteristics of 866 HNSCC cases were comprehensively analyzed. Machine-learning strategies were used to develop a HNSCC cell differentiation score (HCDscore) in order to quantify the unique heterogeneity of individual samples. We also assessed the prognostic value and biological characteristics of HCDscore using the multi-omics data. Results: HNSCCs were stratified into three distinct molecular subtypes based on HDRGs: active stroma (Cluster-A), active metabolism (Cluster-B), and active immune (Cluster-C) types. The three molecular subtypes had different characteristics in terms of biological phenotype, genome and epigenetics, prognosis, immunotherapy and chemotherapy responses. We then demonstrated the correlations between HCDscore and the immune microenvironment, subtypes, carcinogenic biological processes, genetic variation, and prognosis. The low-HCDscore group was characterized by activation of immunity, enhanced response to anti-PD-1/PD-L1 immunotherapy, and better survival compared to the high-HCDscore group. Finally, by integrating the HCDscore with prognostic clinicopathological characteristics, a nomogram with strong predictive performance and high accuracy was constructed. Conclusions: This study revealed that the cell differentiation trajectories in HNSCC played a nonnegligible role in patient prognosis, biological characteristics, and immune responses. Evaluating cancer cell differentiation will help to develop more effective immunotherapy, metabolic therapy, and chemotherapy strategies.

Epidemiological characteristics of hepatic echinococcosis, concurrent cerebral echinococcosis, and pulmonary echinococcosis in Ganzi County, Sichuan Province, China.

Human echinococcosis has become a major public health problem in most parts of the world. The objective of this article was to study the demographics of patients with hepatic echinococcosis in Ganzi County to elucidate the main risk factors, as well as to report the concurrent prevalence of cerebral echinococcosis and pulmonary echinococcosis.We recruited 195 patients with hepatic echinococcosis from the Datongma area of Ganzi County from January 2018 to November 2018. The patients' demographics, living environments, supported medical resources, knowledge of echinococcosis prevention and control, and hygienic practices were investigated and analyzed. The prevalence of cerebral echinococcosis and pulmonary echinococcosis were also investigated.The data were analyzed to identify risk factors for human echinococcosis. Our analysis showed that the herding Tibetan population within the 20 to 60 age group, and females, in particular, were at the highest risk of human echinococcosis infection. Having stray dogs around habitations and intimate activities with dogs and livestock were also behavioral risk factors. People with poor health literacy and low educational qualifications had possible risks of infection. In terms of hygiene, not using tap water as the drinking water source and lack of medical staff were significantly correlated with echinococcosis prevalence. Four patients were diagnosed with cerebral echinococcosis. Among them, 1 patient had both cerebral echinococcosis and pulmonary echinococcosis.Possible high-risk factors for echinococcosis were being female, herding population, in the 20 to 60 age group, having stray dogs around habitations, having activities with dogs and livestock, having poor health literacy, having low educational qualifications, and not using tap water as a drinking water source. The detection rate for brain echinococcosis in patients with hepatic echinococcosis was high (2.05%). Effective preventive strategies should be implemented in epidemic areas. Head CT scans should be applied for early detection of cerebral echinococcosis to carry out the treatment.