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

Zhiyong Li; Yang Liu; Baiqiang Lin; Wei Yan; Huijie Yi; Haoran Wang; Yunwei Wei

doi:10.3389/fgene.2022.925338

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

Front Genet. 2022 Jul 22:13:925338. doi: 10.3389/fgene.2022.925338. eCollection 2022.

Authors

Zhiyong Li^{1

2}, Yang Liu^{1

3}, Baiqiang Lin¹, Wei Yan¹, Huijie Yi^{4

5}, Haoran Wang¹, Yunwei Wei^{1

3}

Affiliations

¹ Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
² Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China.
³ Pancreatic and Gastrointestinal Surgery Division, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China.
⁴ Peking University School of Nursing, Beijing, China.
⁵ Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China.

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.

Keywords: colorectal cancer; genetic alteration; immune cell infiltration; prognostic; pyroptosis; single-cell sequencing.