A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients

A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients

Abstract To identify a gemcitabine resistance-associated gene signature for risk stratification and prognosis prediction in pancreatic cancer. Pearson correlation analysis was performed with gemcitabine half maximal inhibitory concentration (IC50) data of 17 primary pancreatic cancer lines from Geno...

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Autores principales: Xing Wei, Xiaochong Zhou, Yun Zhao, Yang He, Zhen Weng, Chunfang Xu
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/e70d554dfc1c445f9c91725dcebfa00f
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spelling oai:doaj.org-article:e70d554dfc1c445f9c91725dcebfa00f2021-12-02T13:17:56ZA 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients10.1038/s41598-021-85680-x2045-2322https://doaj.org/article/e70d554dfc1c445f9c91725dcebfa00f2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85680-xhttps://doaj.org/toc/2045-2322Abstract To identify a gemcitabine resistance-associated gene signature for risk stratification and prognosis prediction in pancreatic cancer. Pearson correlation analysis was performed with gemcitabine half maximal inhibitory concentration (IC50) data of 17 primary pancreatic cancer lines from Genomics of Drug Sensitivity in Cancer (GDSC) and the transcriptomic data from GDSC and Broad Institute Cancer Cell Line Encyclopedia, followed by risk stratification, expression evaluation, overall survival (OS) prediction, clinical data validation and nomogram establishment. Our biomarker discovery effort identified a 14-gene signature, most of which featured differential expression. The 14-gene signature was associated with poor OS in E-MTAB-6134 (HR 2.37; 95% CI 1.75–3.2; p < 0.0001), pancreatic cancer-Canada (PACA-CA) (HR 1.76; 95% CI 1.31–2.37; p = 0.00015), and 4 other independent validation cohorts: pancreatic cancer-Australia (PACA-AU) (HR 1.9; 95% CI 1.38–2.61; p < 0.0001), The Cancer Genome Atlas (TCGA) (HR 1.73; 95% CI 1.11–2.69; p = 0.014), GSE85916 (HR 1.97; 95% CI 1.14–3.42; p = 0.014) and GSE62452 (HR 1.82; 95% CI 1.02–3.24; p = 0.039). Multivariate analysis revealed that the 14-gene risk score was an independent pancreatic cancer outcome predictor in E-MTAB-6134 (p < 0.001) and TCGA (p = 0.006). A nomogram including the 14-gene was established for eventual clinical translation. We identified a novel gemcitabine resistance gene signature for risk stratification and robust categorization of pancreatic cancer patients with poor prognosis.Xing WeiXiaochong ZhouYun ZhaoYang HeZhen WengChunfang XuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Xing Wei
Xiaochong Zhou
Yun Zhao
Yang He
Zhen Weng
Chunfang Xu
A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients
description Abstract To identify a gemcitabine resistance-associated gene signature for risk stratification and prognosis prediction in pancreatic cancer. Pearson correlation analysis was performed with gemcitabine half maximal inhibitory concentration (IC50) data of 17 primary pancreatic cancer lines from Genomics of Drug Sensitivity in Cancer (GDSC) and the transcriptomic data from GDSC and Broad Institute Cancer Cell Line Encyclopedia, followed by risk stratification, expression evaluation, overall survival (OS) prediction, clinical data validation and nomogram establishment. Our biomarker discovery effort identified a 14-gene signature, most of which featured differential expression. The 14-gene signature was associated with poor OS in E-MTAB-6134 (HR 2.37; 95% CI 1.75–3.2; p < 0.0001), pancreatic cancer-Canada (PACA-CA) (HR 1.76; 95% CI 1.31–2.37; p = 0.00015), and 4 other independent validation cohorts: pancreatic cancer-Australia (PACA-AU) (HR 1.9; 95% CI 1.38–2.61; p < 0.0001), The Cancer Genome Atlas (TCGA) (HR 1.73; 95% CI 1.11–2.69; p = 0.014), GSE85916 (HR 1.97; 95% CI 1.14–3.42; p = 0.014) and GSE62452 (HR 1.82; 95% CI 1.02–3.24; p = 0.039). Multivariate analysis revealed that the 14-gene risk score was an independent pancreatic cancer outcome predictor in E-MTAB-6134 (p < 0.001) and TCGA (p = 0.006). A nomogram including the 14-gene was established for eventual clinical translation. We identified a novel gemcitabine resistance gene signature for risk stratification and robust categorization of pancreatic cancer patients with poor prognosis.
format article
author Xing Wei
Xiaochong Zhou
Yun Zhao
Yang He
Zhen Weng
Chunfang Xu
author_facet Xing Wei
Xiaochong Zhou
Yun Zhao
Yang He
Zhen Weng
Chunfang Xu
author_sort Xing Wei
title A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients
title_short A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients
title_full A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients
title_fullStr A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients
title_full_unstemmed A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients
title_sort 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/e70d554dfc1c445f9c91725dcebfa00f
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