Development and Validation of the Pyroptosis-related genes Signature for Predicting the Prognosis of Colorectal Cancer

Background: Pyroptosis is an important component of the tumor microenvironment, associated with the occurrence and progression of cancer. However, the expression of pyroptosis-related genes and its impact on the prognosis of colon cancer (CC) remains unclear. Here, we constructed and validated a pyroptosis-related genes signature to predict the prognosis of patients with CC.Methods: Public data source was obtained to screen out candidate genes for further analysis. Various methods were combined to construct a robust pyroptosis-related genes signature for predicting the prognosis of patients with CC. Based on the gene signature and clinical features, a decision tree and nomogram were developed to improve risk stratification and quantify risk assessment for individual patients.Results: The pyroptosis-related genes signature successfully discriminated CC patients with high-risk in the training cohorts. The prognostic value of this signature was further confirmed in independent validation cohort. Multivariable Cox regression and stratified survival analysis revealed this signature was an independent prognostic factor for CC patients. The decision tree identified risk subgroups powerfully, and the nomogram incorporating the gene signature and clinical risk factors performed well in the calibration plots.Conclusions: Pyroptosis-related genes signature was an independent prognostic factor, and can be used to predict the prognosis of patients with CC.

[1]  X. Zu,et al.  Siglec15 shapes a non-inflamed tumor microenvironment and predicts the molecular subtype in bladder cancer , 2021, Theranostics.

[2]  Lei Chen,et al.  Acyl-CoA Thioesterase 8 and 11 as Novel Biomarkers for Clear Cell Renal Cell Carcinoma , 2020, Frontiers in Genetics.

[3]  Xianjun Yu,et al.  Ferroptosis, necroptosis, and pyroptosis in anticancer immunity , 2020, Journal of Hematology & Oncology.

[4]  Jing Sun,et al.  Development and validation of a hypoxia-related gene signature to predict overall survival in early-stage lung adenocarcinoma patients , 2020, Therapeutic advances in medical oncology.

[5]  Ji-Hong Liu,et al.  Downregulation of ST3GAL5 is associated with muscle invasion, high grade and a poor prognosis in patients with bladder cancer , 2020, Oncology letters.

[6]  L. Shen,et al.  Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells , 2020, Science.

[7]  Feng-jun Wang,et al.  The role of Caspase-1/GSDMD-mediated pyroptosis in Taxol-induced cell death and a Taxol-resistant phenotype in nasopharyngeal carcinoma regulated by autophagy , 2020, Cell Biology and Toxicology.

[8]  Xi Chen,et al.  Overexpression of GSDMC is a prognostic factor for predicting a poor outcome in lung adenocarcinoma , 2019, Molecular medicine reports.

[9]  Xi Wu,et al.  Pyroptosis: A new frontier in cancer. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[10]  V. Liska,et al.  Expression of Serpin B9 as a Prognostic Factor of Colorectal Cancer , 2019, AntiCancer Research.

[11]  J. Hsieh,et al.  RAB38 is a potential prognostic factor for tumor recurrence in non-small cell lung cancer. , 2019, Oncology letters.

[12]  I. Holen,et al.  Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment , 2019, Clinical Cancer Research.

[13]  B. Liu,et al.  High expression of RAB38 promotes malignant progression of pancreatic cancer , 2018, Molecular medicine reports.

[14]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[15]  S. Amselem,et al.  Photoaging and skin cancer: Is the inflammasome the missing link? , 2018, Mechanisms of Ageing and Development.

[16]  Hyun-Woo Shin,et al.  Cervical cancer is addicted to SIRT1 disarming the AIM2 antiviral defense , 2018, Oncogene.

[17]  Di Chen,et al.  Downregulation of gasdermin D promotes gastric cancer proliferation by regulating cell cycle‐related proteins , 2018, Journal of digestive diseases.

[18]  D. Sargent,et al.  Prognostic Value of Molecular Detection of Lymph Node Metastases After Curative Resection of Stage II Colon Cancer: A Systematic Pooled Data Analysis. , 2015, Clinical colorectal cancer.

[19]  J. Regimbeau,et al.  A lymph node ratio of 10% is predictive of survival in stage III colon cancer: a French regional study. , 2014, International surgery.

[20]  Philip Rosenstiel,et al.  NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. , 2013, The Journal of clinical investigation.

[21]  C. Compton,et al.  Microsatellite instability and loss of heterozygosity at chromosomal location 18q: prospective evaluation of biomarkers for stages II and III colon cancer--a study of CALGB 9581 and 89803. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  Helga Thorvaldsdóttir,et al.  Molecular signatures database (MSigDB) 3.0 , 2011, Bioinform..

[23]  D. Kerr,et al.  Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  R. Labianca,et al.  Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  N. Beauchemin,et al.  Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. , 2010, Immunity.

[26]  Hirokazu Takahashi,et al.  Shape of Barrett's epithelium is associated with prevalence of erosive esophagitis. , 2010, World journal of gastroenterology.

[27]  Ben S. Wittner,et al.  Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 , 2009, Nature.

[28]  D. Kerr,et al.  Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study , 2007, The Lancet.

[29]  Markus Abt,et al.  Capecitabine as adjuvant treatment for stage III colon cancer. , 2005, The New England journal of medicine.

[30]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[31]  Huashan Zhang,et al.  A Novel De ned Pyroptosis-Related Gene Signature For Predicting the Prognosis of Prostate Cancer , 2021 .

[32]  J. Gu,et al.  Upregulation of myosin Va by Snail is involved in cancer cell migration and metastasis , 2010, International journal of cancer.

[33]  G. Landberg,et al.  Expression of the leukotriene D4 receptor CysLT1, COX-2, and other cell survival factors in colorectal adenocarcinomas. , 2003, Gastroenterology.