Abstract
Esophageal adenocarcinoma (EAC) is a highly malignant type of digestive tract cancers with a poor prognosis despite therapeutic advances. Pyroptosis is an inflammatory form of programmed cell death, whereas the role of pyroptosis in EAC remains largely unknown. Herein, we identified a pyroptosis-related five-gene signature that was significantly correlated with the survival of EAC patients in The Cancer Genome Atlas (TCGA) cohort and an independent validation dataset. In addition, a nomogram based on the signature was constructed with novel prognostic values. Moreover, the downregulation of GSDMB within the signature is notably correlated with enhanced DNA methylation. The pyroptosis-related signature might be related to the immune response and regulation of the tumor microenvironment. Several inhibitors including GDC-0879 and PD-0325901 are promising in reversing the altered differentially expressed genes in high-risk patients. Our findings provide insights into the involvement of pyroptosis in EAC progression and are promising in the risk assessment as well as the prognosis for EAC patients in clinical practice.
Highlights
Esophageal cancer is one of the most common malignancies worldwide, accounting for approximately 604,100 new cases and 544,076 deaths per year over the world (Sung et al, 2021)
The expression levels of 58 pyroptosis-correlated genes were examined in the The Cancer Genome Atlas (TCGA) data of 78 Esophageal adenocarcinoma (EAC) and 9 normal tissues
Cell death serves as an essential barrier against the development of cancer, and pyroptosis is one of the major forms of programmed cell death (Bertheloot et al, 2021)
Summary
Esophageal cancer is one of the most common malignancies worldwide, accounting for approximately 604,100 new cases and 544,076 deaths per year over the world (Sung et al, 2021). Esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) composite the principle histologic subtypes of esophageal cancer, in which the incidence of EAC in western countries has increased dramatically in the last decades (Klingelhöfer et al, 2019). Despite therapeutic advances in surgery, radiotherapy, chemotherapy, and targeted drugs, the 5-year survival of esophageal cancer remains less than 20% (Alsop and Sharma, 2016). Pyroptosis is a proinflammatory form of regulated cell death, relying on the enzymatic activity of inflammatory proteases that belong to the caspase family (Vande Walle and Lamkanfi, 2016). Pyroptosis is featured with swift plasma-membrane rupture and subsequent release of proinflammatory intracellular contents, which is distinct from apoptosis (Bergsbaken et al, 2009). Studies evaluating the role of pyroptosis in neurological, infectious, autoimmune, cardiovascular, and oncologic disorders have been
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