Expression patterns and immunological characterization of PANoptosis -related genes in gastric cancer

BackgroundAccumulative studies have demonstrated the close relationship between tumor immunity and pyroptosis, apoptosis, and necroptosis. However, the role of PANoptosis in gastric cancer (GC) is yet to be fully understood.MethodsThis research attempted to identify the expression patterns of PANopt...

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Main Authors: Xin Qing, Junyi Jiang, Chunlei Yuan, Kunke Xie, Ke Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-08-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1222072/full
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author Xin Qing
Xin Qing
Junyi Jiang
Chunlei Yuan
Kunke Xie
Ke Wang
author_facet Xin Qing
Xin Qing
Junyi Jiang
Chunlei Yuan
Kunke Xie
Ke Wang
author_sort Xin Qing
collection DOAJ
description BackgroundAccumulative studies have demonstrated the close relationship between tumor immunity and pyroptosis, apoptosis, and necroptosis. However, the role of PANoptosis in gastric cancer (GC) is yet to be fully understood.MethodsThis research attempted to identify the expression patterns of PANoptosis regulators and the immune landscape in GC by integrating the GSE54129 and GSE65801 datasets. We analyzed GC specimens and established molecular clusters associated with PANoptosis-related genes (PRGs) and corresponding immune characteristics. The differentially expressed genes were determined with the WGCNA method. Afterward, we employed four machine learning algorithms (Random Forest, Support Vector Machine, Generalized linear Model, and eXtreme Gradient Boosting) to select the optimal model, which was validated using nomogram, calibration curve, decision curve analysis (DCA), and two validation cohorts. Additionally, this study discussed the relationship between infiltrating immune cells and variables in the selected model.ResultsThis study identified dysregulated PRGs and differential immune activities between GC and normal samples, and further identified two PANoptosis-related molecular clusters in GC. These clusters demonstrated remarkable immunological heterogeneity, with Cluster1 exhibiting abundant immune infiltration. The Support Vector Machine signature was found to have the best discriminative ability, and a 5-gene-based SVM signature was established. This model showed excellent performance in the external validation cohorts, and the nomogram, calibration curve, and DCA indicated its reliability in predicting GC patterns. Further analysis confirmed that the 5 selected variables were remarkably related to infiltrating immune cells and immune-related pathways.ConclusionTaken together, this work demonstrates that the PANoptosis pattern has the potential as a stratification tool for patient risk assessment and a reflection of the immune microenvironment in GC.
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spelling doaj.art-c5fb06cced374c9684f32374edcabdd62023-08-18T11:24:51ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-08-011410.3389/fendo.2023.12220721222072Expression patterns and immunological characterization of PANoptosis -related genes in gastric cancerXin Qing0Xin Qing1Junyi Jiang2Chunlei Yuan3Kunke Xie4Ke Wang5Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, ChinaWest China Hospital, Sichuan University, Chengdu, ChinaClinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, ChinaClinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, ChinaClinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, ChinaClinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, ChinaBackgroundAccumulative studies have demonstrated the close relationship between tumor immunity and pyroptosis, apoptosis, and necroptosis. However, the role of PANoptosis in gastric cancer (GC) is yet to be fully understood.MethodsThis research attempted to identify the expression patterns of PANoptosis regulators and the immune landscape in GC by integrating the GSE54129 and GSE65801 datasets. We analyzed GC specimens and established molecular clusters associated with PANoptosis-related genes (PRGs) and corresponding immune characteristics. The differentially expressed genes were determined with the WGCNA method. Afterward, we employed four machine learning algorithms (Random Forest, Support Vector Machine, Generalized linear Model, and eXtreme Gradient Boosting) to select the optimal model, which was validated using nomogram, calibration curve, decision curve analysis (DCA), and two validation cohorts. Additionally, this study discussed the relationship between infiltrating immune cells and variables in the selected model.ResultsThis study identified dysregulated PRGs and differential immune activities between GC and normal samples, and further identified two PANoptosis-related molecular clusters in GC. These clusters demonstrated remarkable immunological heterogeneity, with Cluster1 exhibiting abundant immune infiltration. The Support Vector Machine signature was found to have the best discriminative ability, and a 5-gene-based SVM signature was established. This model showed excellent performance in the external validation cohorts, and the nomogram, calibration curve, and DCA indicated its reliability in predicting GC patterns. Further analysis confirmed that the 5 selected variables were remarkably related to infiltrating immune cells and immune-related pathways.ConclusionTaken together, this work demonstrates that the PANoptosis pattern has the potential as a stratification tool for patient risk assessment and a reflection of the immune microenvironment in GC.https://www.frontiersin.org/articles/10.3389/fendo.2023.1222072/fullPANoptosisgastric cancermolecular patternsimmune infiltrationmachine learning
spellingShingle Xin Qing
Xin Qing
Junyi Jiang
Chunlei Yuan
Kunke Xie
Ke Wang
Expression patterns and immunological characterization of PANoptosis -related genes in gastric cancer
Frontiers in Endocrinology
PANoptosis
gastric cancer
molecular patterns
immune infiltration
machine learning
title Expression patterns and immunological characterization of PANoptosis -related genes in gastric cancer
title_full Expression patterns and immunological characterization of PANoptosis -related genes in gastric cancer
title_fullStr Expression patterns and immunological characterization of PANoptosis -related genes in gastric cancer
title_full_unstemmed Expression patterns and immunological characterization of PANoptosis -related genes in gastric cancer
title_short Expression patterns and immunological characterization of PANoptosis -related genes in gastric cancer
title_sort expression patterns and immunological characterization of panoptosis related genes in gastric cancer
topic PANoptosis
gastric cancer
molecular patterns
immune infiltration
machine learning
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1222072/full
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AT chunleiyuan expressionpatternsandimmunologicalcharacterizationofpanoptosisrelatedgenesingastriccancer
AT kunkexie expressionpatternsandimmunologicalcharacterizationofpanoptosisrelatedgenesingastriccancer
AT kewang expressionpatternsandimmunologicalcharacterizationofpanoptosisrelatedgenesingastriccancer