LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma

Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor of the digestive system with increasing morbidity and mortality. The lack of sensitive and reliable biomarkers is one of the main reasons for the poor prognosis. Volume-regulated anion channels (VRAC), which are ubiquitously expressed in t...

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Main Authors: Rong Xu, Yaohua Hu, Qinghua Xie, Caiqin Zhang, Yong Zhao, He Zhang, Hailong Shi, Xiaoming Wang, Changhong Shi
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/22/5526
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author Rong Xu
Yaohua Hu
Qinghua Xie
Caiqin Zhang
Yong Zhao
He Zhang
Hailong Shi
Xiaoming Wang
Changhong Shi
author_facet Rong Xu
Yaohua Hu
Qinghua Xie
Caiqin Zhang
Yong Zhao
He Zhang
Hailong Shi
Xiaoming Wang
Changhong Shi
author_sort Rong Xu
collection DOAJ
description Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor of the digestive system with increasing morbidity and mortality. The lack of sensitive and reliable biomarkers is one of the main reasons for the poor prognosis. Volume-regulated anion channels (VRAC), which are ubiquitously expressed in the vertebrate cell membrane, are composed of leucine-rich repeat-containing 8A (LRRC8A) and four other homologous family members (LRRC8B–E). VRAC heterogeneous complex is implicated in each of the six “hallmarks of cancer” and represents a novel therapeutic target for cancer. In this study, LRRC8A was speculated to be a promising prognostic biomarker and therapeutic target for PAAD based on a series of bioinformatics analyses. Additional cell experiments and immunohistochemical assays demonstrated that LRRC8A can affect the prognosis of PAAD and is correlated to cell proliferation, cell migration, drug resistance, and immune infiltration. Functional analysis indicated that LRRC8A influences the progression and prognosis of patients with PAAD by the regulation of CD8<sup>+</sup> T cells immune infiltration. Taken together, these results can help in the design of new therapeutic drugs for patients with PAAD.
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spelling doaj.art-89f9cdc425f9418a86f0c50f07a79d182023-11-24T07:52:37ZengMDPI AGCancers2072-66942022-11-011422552610.3390/cancers14225526LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic AdenocarcinomaRong Xu0Yaohua Hu1Qinghua Xie2Caiqin Zhang3Yong Zhao4He Zhang5Hailong Shi6Xiaoming Wang7Changhong Shi8Division of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi’an 710032, ChinaDivision of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi’an 710032, ChinaDivision of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi’an 710032, ChinaDivision of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi’an 710032, ChinaDivision of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi’an 710032, ChinaDivision of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi’an 710032, ChinaCollege of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaDepartment of Geriatrics, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, ChinaDivision of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi’an 710032, ChinaPancreatic adenocarcinoma (PAAD) is a highly malignant tumor of the digestive system with increasing morbidity and mortality. The lack of sensitive and reliable biomarkers is one of the main reasons for the poor prognosis. Volume-regulated anion channels (VRAC), which are ubiquitously expressed in the vertebrate cell membrane, are composed of leucine-rich repeat-containing 8A (LRRC8A) and four other homologous family members (LRRC8B–E). VRAC heterogeneous complex is implicated in each of the six “hallmarks of cancer” and represents a novel therapeutic target for cancer. In this study, LRRC8A was speculated to be a promising prognostic biomarker and therapeutic target for PAAD based on a series of bioinformatics analyses. Additional cell experiments and immunohistochemical assays demonstrated that LRRC8A can affect the prognosis of PAAD and is correlated to cell proliferation, cell migration, drug resistance, and immune infiltration. Functional analysis indicated that LRRC8A influences the progression and prognosis of patients with PAAD by the regulation of CD8<sup>+</sup> T cells immune infiltration. Taken together, these results can help in the design of new therapeutic drugs for patients with PAAD.https://www.mdpi.com/2072-6694/14/22/5526pancreatic adenocarcinoma (PAAD)bioinformatics analysesleucine-rich repeat-containing protein 8A (LRRC8A)immune infiltration
spellingShingle Rong Xu
Yaohua Hu
Qinghua Xie
Caiqin Zhang
Yong Zhao
He Zhang
Hailong Shi
Xiaoming Wang
Changhong Shi
LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma
Cancers
pancreatic adenocarcinoma (PAAD)
bioinformatics analyses
leucine-rich repeat-containing protein 8A (LRRC8A)
immune infiltration
title LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma
title_full LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma
title_fullStr LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma
title_full_unstemmed LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma
title_short LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma
title_sort lrrc8a is a promising prognostic biomarker and therapeutic target for pancreatic adenocarcinoma
topic pancreatic adenocarcinoma (PAAD)
bioinformatics analyses
leucine-rich repeat-containing protein 8A (LRRC8A)
immune infiltration
url https://www.mdpi.com/2072-6694/14/22/5526
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