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Deciphering the Pyroptosis-Related Prognostic Signature and Immune Cell Infiltration Characteristics of Colon Cancer

Ran Wei, Shuofeng Li, Guanhua Yu, Xu Guan, Hengchang Liu, Jichuan Quan, Zheng Jiang, Xishan Wang

2021Frontiers in Genetics29 citationsDOIOpen Access PDF

Abstract

Background: Colon cancer (CC) remains one of the most common malignancies with a poor prognosis. Pyroptosis, referred to as cellular inflammatory necrosis, is thought to influence tumor development. However, the potential effects of pyroptosis-related regulators (PRRs) on the CC immune microenvironment remain unknown. Methods: In this study, 27 PRRs reported in the previous study were used to cluster the 1,334 CC samples into three pyroptosis-related molecular patterns. Through subtype pattern differential analysis and structure network mining using Weighted Gene Co-expression Network Analysis (WGCNA), 854 signature genes associated with the PRRs were discovered. Further LASSO-penalized Cox regression of these genes established an eight-gene assessment model for predicting prognosis. Results: The CC patients were subtyped based on three distinct pyroptosis-related molecular patterns. These pyroptosis-related patterns were correlated with different clinical outcomes and immune cell infiltration characteristics in the tumor microenvironment. The pyroptosis-related eight-signature model was established and used to assess the prognosis of CC patients with medium-to-high accuracy by employing the risk scores, which was named “PRM-scores.” Greater inflammatory cell infiltration was observed in tumors with low PRM-scores, indicating a potential benefit of immunotherapy in these patients. Conclusions: This study suggests that PRRs have a significant effect on the tumor immune microenvironment and tumor development. Evaluating the pyroptosis-related patterns and related models will promote our understanding of immune cell infiltration characteristics in the tumor microenvironment and provide a theoretical basis for future research targeting pyroptosis in cancer.

Topics & Concepts

PyroptosisImmune systemTumor microenvironmentInfiltration (HVAC)ImmunotherapyMedicineCancer researchBiologyImmunologyInflammationInflammasomePhysicsThermodynamicsInflammasome and immune disordersFerroptosis and cancer prognosisCancer-related molecular mechanisms research