No abstract

BackgroundCarcinosarcoma is a rare biphasic tumor composed of both carcinoma and sarcoma elements, which occurs at various sites. Most studies are case reports or small population-based studies for a single disease site, so comprehensive evaluations of epidemiology and prognostic factors for carcinosarcoma are needed.MethodsSurveillance, Epidemiology, and End Results (SEER)-8 (1975–2019) provided data for the epidemiological analysis. SEER-17 (2000–2019) provided data on the primary tumor sites, initial treatment, construction, and validation of the nomogram.ResultsThe age-adjusted incidence per 100,000 persons of carcinosarcoma increased significantly from 0.46 to 0.91 [1975–2019; average annual percent change (AAPC): 1.3%, P = 0.006], with localized stage increasing from 0.14 to 0.26 [2005–2015; annual percent change (APC): 4.2%]. The 20-year limited-duration prevalence per 100,000 increased from 0.47 to 3.36 (1999–2018). The mortality per 100,000 increased significantly from 0.16 to 0.51 (1975–2019; AAPC: 1.9%, P < 0.001). The 5-year relative survival was 32.8%. The greatest number of carcinosarcomas were from the uterus (68.7%), ovary (17.8%), lung and bronchus (2.3%). The main treatment is comprehensive treatment based on surgery; however, surgery alone is preferred in older patients. In multivariate analysis (N = 11,424), age, sex, race, year of diagnosis, disease stage, tumor site, and treatment were associated with survival. A nomogram was established to predict 1-, 3-, and 5-year survival, and the C-indexes were 0.732 and 0.748 for the training and testing sets, respectively. The receiver operating characteristic curve demonstrated that the nomogram provided a comprehensive and accurate prediction [1-year area under the curve (AUC): 0.782 vs. 0.796; 3-year AUC: 0.771 vs. 0.798; 5-year AUC: 0.777 vs. 0.810].ConclusionsIn this study, the incidence, prevalence, and mortality of carcinosarcoma have increased over the past decades. There was a rapid rise in the incidence of localized stage in recent years, which reflected improved early detection. The prognosis of carcinosarcoma remains poor, signifying the urgency of exploring targeted cancer control treatments. Explicating distribution and gender disparities of carcinosarcoma may facilitate disease screening and medical surveillance. The nomogram demonstrated good predictive capacity and facilitated clinical decision-making.

Thorase belongs to the AAA+ ATPase family, which plays a critical role in maintaining cellular homeostasis. Our previous work reported that Thorase was highly expressed in brain tissue, especially in the cerebellum. However, the roles of Thorase in the cerebellum have still not been characterized. In this study, we generated conditional knockout mice (cKO) with Thorase deletion in Purkinje cells. Thorase cKO mice exhibited cerebellar degenerative diseases-like behavior and significant impairment in motor coordination. Thorase deletion resulted in more Purkinje neuron apoptosis, leading to Purkinje cell loss in the cerebellum of Thorase cKO mice. We also found enhanced expression of the inflammatory protein ASC, IL-1β, IL-6 and TNF-α in the Thorase cKO cerebellum, which contributed to the pathogenesis of cerebellar degenerative disease. Our findings provide a better understanding of the role of Thorase in the cerebellum, which is a theoretical basis for Thorase as a therapeutic drug target for neurodegenerative diseases.

No abstract