Affiliation:
1. Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2. Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Center for Digestive Diseases Research and Clinical Translation of Shanghai Jiao Tong University, China
3. Department of Forensic Medicine, Shanghai Medical College of Fudan University, Shanghai, China
Abstract
Pyroptosis is a programmed cell death, which garners increasing attention by relating to immune and therapy response. However, the role of pyroptosis in colorectal cancer (CRC) remains unclear. Our study mainly to explore the role of pyroptosis in CRC. The mRNA expression data and corresponding clinical information of CRC patients were achieved from The Cancer Genome Atlas (TCGA). Pyroptosis-related genes (PRGs) were identified using DESeq2 R package and biological function was analyzed using cluster Profiler R package. A PRGs-based prognosis model was constructed by a univariate Cox and LASSO regression analyses. Then, the affecting of risk signature to clinicopathological characteristics, immune status and infiltrated immune cells, immune checkpoint and chemotherapy sensitivity was analyzed. qRT-PCR and IHC were performed for the expression level of PRGs. Moreover, a nomogram predict model was constructed. Total 57 PRGs were identified between 500 CRC samples and 44 normal samples. Those PRGs mainly enriched in immune-related and pyroptosis-related pathways. GABRD, NADK, TMEM240, RER1, AGRN, UBE2J2, CALML6, PLCH2, TMEM88B have been identified as gene signature and a prognostic model was constructed and validated. CRC patients with high-risk score showed poor survival, high TMB score, high proportion of CD4 + memory T cells, common lymphoid progenitors, cancer associated fibroblasts, mast cells, and neutrophils. The immune checkpoint related genes, CD160, CD200R1, CD244, CD28, CD40LG, CD44, CD48, CD80, CD86, HHLA2, ICOS, IDO1, TIGIT, TNFRSF25, TNFRSF4, TNFRSF9, TNFSF15, TNFSF18 also increased in high-risk score group. CRC patients with high-risk score more sensitive to docetaxel and rapamycin but resistance to gemcitabine and mitomycin. Moreover, a predictive nomogram for 1-, 3-, 5-year for CRC patients was established and validated. In the study, a PRGs-based prognostic model and a predictive model were constructed. These models are effective and robust in prediction the 1-, 3-, and 5-year survival of CRC patients.
Funder
Cross disciplinary Research Fund of Shanghai JiaoTong University
Fundamental research program funding of Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Cross disciplinary Research Fund of Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine