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High WFDC3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: A study using the TCGA database and bioinformatics analysis

Whey-acidic-protein (WAP) four-disulfide core domain protein 3 (WFDC3) is one of the WAP family proteins. This protein family is associated with the development of solid tumors and affects the tumor immunological microenvironment. However, the prognostic value of WFDC3 in pancreatic adenocarcinoma (...

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Autores principales: Wu, Wei, Wang, Jiayuan, Hu, Zhiping, Zhao, Yiguo, Wang, Xin, Bai, Nan, Chen, Lei, Gao, Pengji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10589585/
https://www.ncbi.nlm.nih.gov/pubmed/37861515
http://dx.doi.org/10.1097/MD.0000000000035595
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author Wu, Wei
Wang, Jiayuan
Hu, Zhiping
Zhao, Yiguo
Wang, Xin
Bai, Nan
Chen, Lei
Gao, Pengji
author_facet Wu, Wei
Wang, Jiayuan
Hu, Zhiping
Zhao, Yiguo
Wang, Xin
Bai, Nan
Chen, Lei
Gao, Pengji
author_sort Wu, Wei
collection PubMed
description Whey-acidic-protein (WAP) four-disulfide core domain protein 3 (WFDC3) is one of the WAP family proteins. This protein family is associated with the development of solid tumors and affects the tumor immunological microenvironment. However, the prognostic value of WFDC3 in pancreatic adenocarcinoma (PAAD) and its effect on the tumor immune microenvironment is yet to be clarified. The Cancer Genome Atlas database and Genotype-Tissue Expression database were used to analyze the differential expression of WFDC3 between the tumor and adjacent tissues. The clinical significance of WFDC3 was analyzed in The Cancer Genome Atlas and International Cancer Genome Consortium database using WFDC3 transcripts and clinical information. In order to elucidate the underlying mechanisms, gene set enrichment analysis was conducted to determine potential activated pathways. Immune score evaluation and publicly available pharmacogenomics database [the Genomics of Drug Sensitivity in Cancer] were utilized to quantify immune cell infiltration and the effect on chemotherapeutic drug sensitivity. WFDC3 levels were higher in PAAD tissues than in normal pancreatic tissues. High levels of WFDC3 expression progressively increased as PAAD tumor stages progressed. Patients with elevated WFDC3 expression showed a poor prognosis. The gene set enrichment analysis analysis revealed that glutamate, arginine, and proline, and histidine metabolism levels were elevated in patients with a high WFDC3 expression phenotype. B, CD4(+) T, and CD8(+) T cell infiltration was diminished in PAAD tissues with elevated WFDC3 expression. According to pharmacogenomics, PAAD tissues with high WFDC3 expression are susceptible to gemcitabine. WFDC3 is highly expressed in PAAD, and patients with a high level of WFDC3 expression have a shorter overall survival time, indicating a poorer prognosis. High expression of WFDC3 may lead to the development of PAAD by affecting the amino acid metabolism and the tumor immunological microenvironment. WFDC3 may serve as a potential diagnostic and prognostic biomarker for PAAD patients.
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spelling pubmed-105895852023-10-22 High WFDC3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: A study using the TCGA database and bioinformatics analysis Wu, Wei Wang, Jiayuan Hu, Zhiping Zhao, Yiguo Wang, Xin Bai, Nan Chen, Lei Gao, Pengji Medicine (Baltimore) 5700 Whey-acidic-protein (WAP) four-disulfide core domain protein 3 (WFDC3) is one of the WAP family proteins. This protein family is associated with the development of solid tumors and affects the tumor immunological microenvironment. However, the prognostic value of WFDC3 in pancreatic adenocarcinoma (PAAD) and its effect on the tumor immune microenvironment is yet to be clarified. The Cancer Genome Atlas database and Genotype-Tissue Expression database were used to analyze the differential expression of WFDC3 between the tumor and adjacent tissues. The clinical significance of WFDC3 was analyzed in The Cancer Genome Atlas and International Cancer Genome Consortium database using WFDC3 transcripts and clinical information. In order to elucidate the underlying mechanisms, gene set enrichment analysis was conducted to determine potential activated pathways. Immune score evaluation and publicly available pharmacogenomics database [the Genomics of Drug Sensitivity in Cancer] were utilized to quantify immune cell infiltration and the effect on chemotherapeutic drug sensitivity. WFDC3 levels were higher in PAAD tissues than in normal pancreatic tissues. High levels of WFDC3 expression progressively increased as PAAD tumor stages progressed. Patients with elevated WFDC3 expression showed a poor prognosis. The gene set enrichment analysis analysis revealed that glutamate, arginine, and proline, and histidine metabolism levels were elevated in patients with a high WFDC3 expression phenotype. B, CD4(+) T, and CD8(+) T cell infiltration was diminished in PAAD tissues with elevated WFDC3 expression. According to pharmacogenomics, PAAD tissues with high WFDC3 expression are susceptible to gemcitabine. WFDC3 is highly expressed in PAAD, and patients with a high level of WFDC3 expression have a shorter overall survival time, indicating a poorer prognosis. High expression of WFDC3 may lead to the development of PAAD by affecting the amino acid metabolism and the tumor immunological microenvironment. WFDC3 may serve as a potential diagnostic and prognostic biomarker for PAAD patients. Lippincott Williams & Wilkins 2023-10-20 /pmc/articles/PMC10589585/ /pubmed/37861515 http://dx.doi.org/10.1097/MD.0000000000035595 Text en Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) (https://creativecommons.org/licenses/by-nc/4.0/) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
spellingShingle 5700
Wu, Wei
Wang, Jiayuan
Hu, Zhiping
Zhao, Yiguo
Wang, Xin
Bai, Nan
Chen, Lei
Gao, Pengji
High WFDC3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: A study using the TCGA database and bioinformatics analysis
title High WFDC3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: A study using the TCGA database and bioinformatics analysis
title_full High WFDC3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: A study using the TCGA database and bioinformatics analysis
title_fullStr High WFDC3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: A study using the TCGA database and bioinformatics analysis
title_full_unstemmed High WFDC3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: A study using the TCGA database and bioinformatics analysis
title_short High WFDC3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: A study using the TCGA database and bioinformatics analysis
title_sort high wfdc3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: a study using the tcga database and bioinformatics analysis
topic 5700
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10589585/
https://www.ncbi.nlm.nih.gov/pubmed/37861515
http://dx.doi.org/10.1097/MD.0000000000035595
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