Pyroptosis-Related Signature as Potential Biomarkers for Predicting Prognosis and Therapy Response in Colorectal Cancer Patients

Abstract

Background: Abnormal mucosal inflammation is a critical risk factor for pathogenesis and progression of colorectal cancer (CRC). As a type of proinflammatory death, pyroptosis can recast a suitable microenvironment to promote tumor growth. However, the potential role of pyroptosis in CRC remains unclear.Methods: A total of 38 pyroptosis-related gene (PRG) expression profiles and clinical information were collected from multiple public datasets. Bioinformatics methods were used to analyze the clinical significance, functional status, immune infiltration, genomic alteration, and drug sensitivity in different subgroups. Whole-genome microarray analysis was performed to analyze the regulation of gut microbiota on the expression of PRGs.Results: Two distinct molecular subtypes were identified and suggested that multilayer PRG alterations were associated with patient clinicopathological features, prognosis, and tumor microenvironment (TME) infiltrating characteristics. Furthermore, we obtained eight PRG signatures by applying differential expression analysis and univariate Cox and Lasso regression analyses. A risk prognosis model was constructed for predicting overall survival (OS) and recurrence-free survival (RFS) based on the PRG signature. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high- and low-risk groups. In addition, the PRG signature was significantly associated with the microsatellite instability (MSI), tumor mutation burden (TMB), cancer stem cell (CSC) index, immunotherapeutic characteristics, and chemotherapeutic drug sensitivity. Moreover, the in vitro experiments had shown that Fusobacterium nucleatum (F.n) could affect the CASP6 expression, which was associated with the chemoresistance to 5-fluorouracil (5-Fu) in CRC.Conclusion: Our findings provided a foundation for future research targeting pyroptosis and a new insight into the prognosis and immune cell infiltration of CRC, and they suggested that F.n might influence CRC progression through pyroptosis.

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.…”

IL-17A-mediated mitochondrial dysfunction induces pyroptosis in colorectal cancer cells and promotes CD8 + T-cell tumour infiltration

“…Numerous studies have revealed that pyroptosis-related genes (PRGs) in CRC demonstrated their potential roles in the tumour-immune-stromal microenvironment, clinicopathological features, and prognosis [ 25 , 26 ]. Pyroptosis in tumour cells would enhance the tumouricidal effect, various chemotherapeutic drugs can kill colorectal cancer cells via canonical or non-canonical pyroptosis [ 27 , 28 ].…”

Clinical value of anoikis-related genes and molecular subtypes identification in bladder urothelial carcinoma and in vitro validation

“…There is more evidence that CALR is associated with cell carcinogenesis, drug resistance of tumor cells, and epithelial-mesenchymal transformation ( 17 ). The study found that Casp6 in cancerous tissues was low expression, indicating that it had a certain inhibitory potential in tumorigenesis and progression ( 18 ). and the expression level of Casp6 was inversely correlated with the IC50 value of 5fluorouracil ( 19 , 20 ).…”