Pyroptosis: A promising biomarker for predicting colorectal cancer prognosis and enhancing immunotherapy efficacy

Table 1 Differences between pyroptosis and apoptosis

	Apoptosis[5-9]	Pyroptosis[1,2,19-21]
Definition	The orderly death of cells autonomously controlled by genes in order to maintain a stable internal environment	An inflammatory programmed cell death triggered by various pathological stimuli, such as stroke, heart attack, cancer, and microbial infection
Trigger factor	Gene regulation under physiological conditions	Pathological stimulation
Cell morphological changes	The cell size is usually reduced, the cell membrane structure is intact, and the organelles are intact	The cell size is usually enlarged and cell morphology is deformed, the cell membrane is broken, and the organelles are deformed
Marker events	Nucleoprotein, cytoskeleton, and protein crosslinking are destroyed, phagocyte ligands are expressed, and apoptotic bodies are formed	The nucleus is concentrated and pyrosome is formed
DNA change	DNA is degraded into fragments of 180-200 bp and its integral multiples	DNA is randomly degraded
Molecular mechanism	Caspase-2/3/6/7/8/9/10, in which caspase-3 is the main regulator of apoptosis	Human caspase-1/4/5; murine caspase-1/11
Detection indexes	Early apoptosis detection indicators: Annexin V and JC-1; metaphase apoptosis detection index: Caspase; late apoptotic detection index: TUNEL staining	No specific detection indicators, but the cell morphology could be observed by scanning electron microscopy and TUNEL staining, GSDMD immunofluorescence staining could be used to detect the expression levels of pyro related genes or proteins (caspase-1/4/5/11, etc.), and the levels of inflammatory factors (IL-1β, IL-18, etc.) could be detected by ELISA. CCK-8 assay can be used to determine cell viability
Dependency	The endogenous pathway (also called the mitochondrial pathway) is based on caspase-9	Classical pathway: Based on caspase-1; nonclassical pathway: Based on caspase-4/5/11