Pyroptosis is related to immune infiltration and predictive for survival of colon adenocarcinoma patients

Abstract

Pyroptosis is a novel type of programmed cell death, initiated by inflammasome. Pyroptosis inhibits the development and metastasis of colon cancer and is associated with patients’ prognosis. However, how the pyroptosis-related genes predict the survival of patients is still unclear. In the study, colon adenocarcinoma (COAD) patients were divided into two groups according to the expression of pyroptosis-related regulators through consensus clustering. DEGs between two clusters were analyzed by using COX and Lasso regression. Then, regression coefficients in Lasso were used to calculate the risk score for every patient. Patients were classified into two types: low- and high-risk group according to their risk score. The difference of immune microenvironment infiltration and clinicopathological characteristics between subgroups was performed. Moreover, the nomogram model was built on the bases of risk model and clinicopathological factors. The TCGA-COAD cohort and GEO cohort were used as training and validating set respectively. 398 COAD patients in TCGA training set were identified as two regulation patterns via unsupervised clustering method. Patients in cluster 2 showed better prognosis (P = 0.002). Through differentiated expression analysis, COX and Lasso regression, a 5-gene prognostic risk model was constructed. This risk model was significantly associated with OS (HR: 2.088, 95% CI: 1.183–3.688, P = 0.011), validated in GEO set (HR:1.344, 95%CI: 1.061–1.704, P = 0.014), and patients with low risk had better prognosis (P < 0.001 in TCGA; P = 0.038 in GEO). Through ROC analysis, it can be found that this model presented better predictive accuracy for long-term survival. Clinical analyses demonstrated that high-risk group had more advanced N stage, higher risk of metastasis and later pathological stage. Immune-related analysis illustrated that low-risk group had more immune cell infiltration and more activated immune pathways. The pyroptosis-related risk model can be predictive for the survival of COAD patients. That patients with higher risk had poorer prognosis was associated with more advanced tumor stage and higher risk of metastasis, and resulted from highly activated pro-tumor pathways and inhibited immune system and poorer integrity of intestinal epithelial. This study proved the relationship between pyroptosis and immune, which offered basis for future studies.

Correlation of gasdermin B staining patterns with prognosis, progression, and immune response in colorectal cancer

“…In another study on GSDMB expression in CRC, Lu et al [ 37 ] clustered TCGA-colon adenocarcinoma based on 12 pyroptosis-related regulators. The cluster with the highest GSDMB expression—which was linked to a higher number of activated CD8 + T cells, dendritic cells, macrophages, NK cells, and helper T cells—showed a better prognosis than the other cluster, which was related to advanced N stage.…”

Identification and validation of a pyroptosis-related prognostic model for colorectal cancer based on bulk and single-cell RNA sequencing data

“…This study specifically investigated the regulatory function of pyroptosis-related genes on immune infiltration. CD4+ T cells are key participants in anti-tumor immune responses and significantly impact CRC prognosis[ 64 - 67 ]. Previous studies have highlighted that activated memory CD4+ T cells exhibit infiltrative and antitumor effects during the early stages of CRC progression[ 68 ], while infiltration of memory resting CD4+ T cells is associated with a favorable prognosis[ 69 ].…”

Experimental prognostic model integrating N6-methyladenosine-related programmed cell death genes in colorectal cancer

“… 45 While the roles of various programmed cell death (PCD) modes in CRC prognosis have been explored in the literature, these models have primarily focused on individual modes of cell death, such as the apoptosis-related prognostic signature, 46 autophagy-related signature, 47 , 48 , 49 , 50 , 51 cuproptosis-related signature, 52 , 53 , 54 ferroptosis-related signature, 55 , 56 , 57 necroptosis-related signature, 58 , 59 and pyroptosis-related prognostic signature. 60 , 61 , 62 , 63 , 64 , 65 However, the interplay between m6A modification and PCD in CRC prognosis remains unexplored, representing a gap in the existing literature. In this study, we identified 854 m6A-related PCD genes through Pearson correlation analysis and then selected 10 prognosis-related genes through univariate and multivariate Cox proportional hazard regression.…”