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Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma

BACKGROUND: Acidosis in the tumor microenvironment (TME) is involved in tumor immune dysfunction and tumor progression. We attempted to develop an acidosis-related index (ARI) signature to improve the prognostic prediction of pancreatic carcinoma (PC). METHODS: Differential gene expression analyses...

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Autores principales: Tang, Pingfei, Qu, Weiming, Wu, Dajun, Chen, Shihua, Liu, Minji, Chen, Weishun, Ai, Qiongjia, Tang, Haijuan, Zhou, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727107/
https://www.ncbi.nlm.nih.gov/pubmed/34993253
http://dx.doi.org/10.1155/2021/3821055
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author Tang, Pingfei
Qu, Weiming
Wu, Dajun
Chen, Shihua
Liu, Minji
Chen, Weishun
Ai, Qiongjia
Tang, Haijuan
Zhou, Hongbing
author_facet Tang, Pingfei
Qu, Weiming
Wu, Dajun
Chen, Shihua
Liu, Minji
Chen, Weishun
Ai, Qiongjia
Tang, Haijuan
Zhou, Hongbing
author_sort Tang, Pingfei
collection PubMed
description BACKGROUND: Acidosis in the tumor microenvironment (TME) is involved in tumor immune dysfunction and tumor progression. We attempted to develop an acidosis-related index (ARI) signature to improve the prognostic prediction of pancreatic carcinoma (PC). METHODS: Differential gene expression analyses of two public datasets (GSE152345 and GSE62452) from the Gene Expression Omnibus database were performed to identify the acidosis-related genes. The Cancer Genome Atlas–pancreatic carcinoma (TCGA-PAAD) cohort in the TCGA database was set as the discovery dataset. Univariate Cox regression and the Kaplan–Meier method were applied to screen for prognostic genes. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish the optimal model. The tumor immune infiltrating pattern was characterized by the single-sample gene set enrichment analysis (ssGSEA) method, and the prediction of immunotherapy responsiveness was conducted using the tumor immune dysfunction and exclusion (TIDE) algorithm. RESULTS: We identified 133 acidosis-related genes, of which 37 were identified as prognostic genes by univariate Cox analysis in combination with the Kaplan–Meier method (p values of both methods < 0.05). An acidosis-related signature involving seven genes (ARNTL2, DKK1, CEP55, CTSV, MYEOV, DSG2, and GBP2) was developed in TCGA-PAAD and further validated in GSE62452. Patients in the acidosis-related high-risk group consistently showed poorer survival outcomes than those in the low-risk group. The 5-year AUCs (areas under the curve) for survival prediction were 0.738 for TCGA-PAAD and 0.889 for GSE62452, suggesting excellent performance. The low-risk group in TCGA-PAAD showed a higher abundance of CD8+ T cells and activated natural killer cells and was predicted to possess an elevated proportion of immunotherapeutic responders compared with the high-risk counterpart. CONCLUSIONS: We developed a reliable acidosis-related signature that showed excellent performance in prognostic prediction and correlated with tumor immune infiltration, providing a new direction for prognostic evaluation and immunotherapy management in PC.
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spelling pubmed-87271072022-01-05 Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma Tang, Pingfei Qu, Weiming Wu, Dajun Chen, Shihua Liu, Minji Chen, Weishun Ai, Qiongjia Tang, Haijuan Zhou, Hongbing J Immunol Res Research Article BACKGROUND: Acidosis in the tumor microenvironment (TME) is involved in tumor immune dysfunction and tumor progression. We attempted to develop an acidosis-related index (ARI) signature to improve the prognostic prediction of pancreatic carcinoma (PC). METHODS: Differential gene expression analyses of two public datasets (GSE152345 and GSE62452) from the Gene Expression Omnibus database were performed to identify the acidosis-related genes. The Cancer Genome Atlas–pancreatic carcinoma (TCGA-PAAD) cohort in the TCGA database was set as the discovery dataset. Univariate Cox regression and the Kaplan–Meier method were applied to screen for prognostic genes. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish the optimal model. The tumor immune infiltrating pattern was characterized by the single-sample gene set enrichment analysis (ssGSEA) method, and the prediction of immunotherapy responsiveness was conducted using the tumor immune dysfunction and exclusion (TIDE) algorithm. RESULTS: We identified 133 acidosis-related genes, of which 37 were identified as prognostic genes by univariate Cox analysis in combination with the Kaplan–Meier method (p values of both methods < 0.05). An acidosis-related signature involving seven genes (ARNTL2, DKK1, CEP55, CTSV, MYEOV, DSG2, and GBP2) was developed in TCGA-PAAD and further validated in GSE62452. Patients in the acidosis-related high-risk group consistently showed poorer survival outcomes than those in the low-risk group. The 5-year AUCs (areas under the curve) for survival prediction were 0.738 for TCGA-PAAD and 0.889 for GSE62452, suggesting excellent performance. The low-risk group in TCGA-PAAD showed a higher abundance of CD8+ T cells and activated natural killer cells and was predicted to possess an elevated proportion of immunotherapeutic responders compared with the high-risk counterpart. CONCLUSIONS: We developed a reliable acidosis-related signature that showed excellent performance in prognostic prediction and correlated with tumor immune infiltration, providing a new direction for prognostic evaluation and immunotherapy management in PC. Hindawi 2021-12-28 /pmc/articles/PMC8727107/ /pubmed/34993253 http://dx.doi.org/10.1155/2021/3821055 Text en Copyright © 2021 Pingfei Tang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Tang, Pingfei
Qu, Weiming
Wu, Dajun
Chen, Shihua
Liu, Minji
Chen, Weishun
Ai, Qiongjia
Tang, Haijuan
Zhou, Hongbing
Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma
title Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma
title_full Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma
title_fullStr Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma
title_full_unstemmed Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma
title_short Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma
title_sort identifying and validating an acidosis-related signature associated with prognosis and tumor immune infiltration characteristics in pancreatic carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727107/
https://www.ncbi.nlm.nih.gov/pubmed/34993253
http://dx.doi.org/10.1155/2021/3821055
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