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Published on: January 19, 2019
Genomic and Immunological Characterization of Pyroptosis in Lung Adenocarcinoma
Yaobo Song1, Zhen Qu2, Hu Feng3
1Department of Medical Oncology Ward, Yantaishan Hospital, Yantai 264001, China.
Abstract:
Pyroptosis is a programmed cell death that may either promote or hinder cancer growth under different circumstances. Pyroptosis-related genes (PRGs) could be a useful target for cancer therapy, and are uncommon in lung adenocarcinoma (LUAD). The expression profiles, mutation data and clinical information of LUAD patients were included in this study. A pyroptosis-related prognostic risk score (PPRS) model was constructed by performing Cox regression, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis to score LUAD patients. Somatic mutation and copy number variation (CNV), tumor immunity, and sensitivity to immunotherapy/chemotherapy were compared between different PPRS groups. Clinical parameters of LUAD were combined with PPRS to construct a decision tree and nomogram. Red module was highly positively correlated with pyroptosis. Seven genes (FCRLB, COTL1, GNG10, CASP4, DOK1, CCR2, and AQP8) were screened from the red module to construct a PPRS model. Significantly lower overall survival (OS), higher incidence of somatic mutation and CNV, elevated infiltration level of the immune cell together with increased probability of immune escape were observed in LUAD patients with higher PPRS, and were more sensitive to Cisplatin, Docetaxel, and Vinorelbine. We constructed a new PPRS model for patients with LUAD. The model might have clinical significance in the prediction of the prognosis of patients with LUAD and in the efficacy of chemotherapy and immunotherapy.
Insights
This study developed a pyroptosis-related prognostic risk score (PPRS) model for lung adenocarcinoma (LUAD). The PPRS model predicts patient survival and chemotherapy/immunotherapy response in LUAD.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pyroptosis, a programmed cell death, has complex roles in cancer, potentially promoting or hindering tumor growth.
- Pyroptosis-related genes (PRGs) are infrequently found in lung adenocarcinoma (LUAD) but represent potential therapeutic targets.
Purpose of the Study:
- To construct and validate a pyroptosis-related prognostic risk score (PPRS) model for LUAD patients.
- To investigate the association between the PPRS model and clinical parameters, tumor immunity, and treatment sensitivity in LUAD.
Main Methods:
- Utilized Cox regression, weighted gene co-expression network analysis (WGCNA), and LASSO regression to identify PRGs and build the PPRS model.
- Analyzed expression profiles, mutation data, and clinical information of LUAD patients.
- Compared somatic mutations, copy number variations (CNVs), tumor immunity, and treatment sensitivity across different PPRS groups.
Main Results:
- A seven-gene PPRS model (FCRLB, COTL1, GNG10, CASP4, DOK1, CCR2, AQP8) was constructed, with the 'red module' strongly correlating with pyroptosis.
- Higher PPRS scores in LUAD patients were linked to significantly lower overall survival (OS), increased somatic mutation and CNV rates, and elevated immune cell infiltration.
- Patients with higher PPRS exhibited a greater probability of immune escape and showed increased sensitivity to chemotherapies like Cisplatin, Docetaxel, and Vinorelbine.
Conclusions:
- The developed PPRS model offers a novel tool for predicting prognosis in LUAD patients.
- The PPRS model may guide clinical decisions regarding chemotherapy and immunotherapy efficacy in LUAD treatment.

