Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer

Background: Cell Cycle-Associated Protein 1 (CAPRIN1) play an important role in cell proliferation, oxidative stress, and inflammatory response. Nonetheless, its role in tumor immunity and ferroptosis is largely unknown in gastrointestinal cancer patients. Methods: Through comprehensive bioinformati...

Full description

Bibliographic Details
Main Authors: Yan Gao, Ruimin Wu, Zhijun Pei, Changbin Ke, Daobing Zeng, Xiaohui Li, Yanmin Zhang
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024048254
_version_ 1797234051815309312
author Yan Gao
Ruimin Wu
Zhijun Pei
Changbin Ke
Daobing Zeng
Xiaohui Li
Yanmin Zhang
author_facet Yan Gao
Ruimin Wu
Zhijun Pei
Changbin Ke
Daobing Zeng
Xiaohui Li
Yanmin Zhang
author_sort Yan Gao
collection DOAJ
description Background: Cell Cycle-Associated Protein 1 (CAPRIN1) play an important role in cell proliferation, oxidative stress, and inflammatory response. Nonetheless, its role in tumor immunity and ferroptosis is largely unknown in gastrointestinal cancer patients. Methods: Through comprehensive bioinformatics, we investigate CAPRIN1 expression patterns and its role in diagnosis, functional signaling pathways, tumor immune infiltration and ferroptosis of different gastrointestinal cancer subtypes. Besides, immunohistochemistry (IHC) and immune blot were used to validate our esophagus cancer clinical data. The ferroptotic features of CAPRIN1 in vitro were assessed through knockdown assays in esophagus cancer cells. Results: CAPRIN1 expression was significantly upregulated, correlated with poor prognosis, and served as an independent risk factor for most gastrointestinal cancer. Moreover, CAPRIN1 overexpression positively correlated with gene markers of most infiltrating immune cells, and immune checkpoints. CAPRIN1 knockdown significantly decreased the protein level of major histocompatibility complex class I molecules. We also identified a link between CAPRIN1 and ferroptosis-related genes in gastrointestinal cancer. Knockdown of CAPRIN1 significantly increased the production of lipid reactive oxygen species and malondialdehyde. Inhibition of CAPRIN1 expression promoted ferroptotic cell death induced by RAS-selective lethal 3 and erastin in human esophagus cancer cells. Conclusion: Collectively, our results demonstrate that CAPRIN1 is aberrantly expressed in gastrointestinal cancer, is associated with poor prognosis, and could potentially influence immune infiltration and ferroptosis.
first_indexed 2024-04-24T16:25:55Z
format Article
id doaj.art-8e4a9c65b8d14fb2bb50f790fdb8b5aa
institution Directory Open Access Journal
issn 2405-8440
language English
last_indexed 2024-04-24T16:25:55Z
publishDate 2024-04-01
publisher Elsevier
record_format Article
series Heliyon
spelling doaj.art-8e4a9c65b8d14fb2bb50f790fdb8b5aa2024-03-31T04:37:41ZengElsevierHeliyon2405-84402024-04-01107e28794Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancerYan Gao0Ruimin Wu1Zhijun Pei2Changbin Ke3Daobing Zeng4Xiaohui Li5Yanmin Zhang6Department of Pharmacy, Taihe Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, P.R. China; Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, ChinaDepartment of Pharmacy, Taihe Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, ChinaDepartment of Pharmacy, Taihe Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, ChinaDepartment of Pharmacy, Taihe Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, ChinaDepartment of Pharmacy, Taihe Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, ChinaDepartment of Pharmacy, Taihe Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, ChinaSchool of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, P.R. China; State Key Laboratory of Shaanxi for Natural Medicines Research and Engineering, Xi'an Jiaotong University, Xi'an, 710061, China; Corresponding author. School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province, 710061, China.Background: Cell Cycle-Associated Protein 1 (CAPRIN1) play an important role in cell proliferation, oxidative stress, and inflammatory response. Nonetheless, its role in tumor immunity and ferroptosis is largely unknown in gastrointestinal cancer patients. Methods: Through comprehensive bioinformatics, we investigate CAPRIN1 expression patterns and its role in diagnosis, functional signaling pathways, tumor immune infiltration and ferroptosis of different gastrointestinal cancer subtypes. Besides, immunohistochemistry (IHC) and immune blot were used to validate our esophagus cancer clinical data. The ferroptotic features of CAPRIN1 in vitro were assessed through knockdown assays in esophagus cancer cells. Results: CAPRIN1 expression was significantly upregulated, correlated with poor prognosis, and served as an independent risk factor for most gastrointestinal cancer. Moreover, CAPRIN1 overexpression positively correlated with gene markers of most infiltrating immune cells, and immune checkpoints. CAPRIN1 knockdown significantly decreased the protein level of major histocompatibility complex class I molecules. We also identified a link between CAPRIN1 and ferroptosis-related genes in gastrointestinal cancer. Knockdown of CAPRIN1 significantly increased the production of lipid reactive oxygen species and malondialdehyde. Inhibition of CAPRIN1 expression promoted ferroptotic cell death induced by RAS-selective lethal 3 and erastin in human esophagus cancer cells. Conclusion: Collectively, our results demonstrate that CAPRIN1 is aberrantly expressed in gastrointestinal cancer, is associated with poor prognosis, and could potentially influence immune infiltration and ferroptosis.http://www.sciencedirect.com/science/article/pii/S2405844024048254CAPRIN1FerroptosisImmune infiltratesPrognosisGastrointestinal cancer
spellingShingle Yan Gao
Ruimin Wu
Zhijun Pei
Changbin Ke
Daobing Zeng
Xiaohui Li
Yanmin Zhang
Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer
Heliyon
CAPRIN1
Ferroptosis
Immune infiltrates
Prognosis
Gastrointestinal cancer
title Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer
title_full Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer
title_fullStr Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer
title_full_unstemmed Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer
title_short Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer
title_sort cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer
topic CAPRIN1
Ferroptosis
Immune infiltrates
Prognosis
Gastrointestinal cancer
url http://www.sciencedirect.com/science/article/pii/S2405844024048254
work_keys_str_mv AT yangao cellcycleassociatedprotein1associateswithimmuneinfiltrationandferroptosisingastrointestinalcancer
AT ruiminwu cellcycleassociatedprotein1associateswithimmuneinfiltrationandferroptosisingastrointestinalcancer
AT zhijunpei cellcycleassociatedprotein1associateswithimmuneinfiltrationandferroptosisingastrointestinalcancer
AT changbinke cellcycleassociatedprotein1associateswithimmuneinfiltrationandferroptosisingastrointestinalcancer
AT daobingzeng cellcycleassociatedprotein1associateswithimmuneinfiltrationandferroptosisingastrointestinalcancer
AT xiaohuili cellcycleassociatedprotein1associateswithimmuneinfiltrationandferroptosisingastrointestinalcancer
AT yanminzhang cellcycleassociatedprotein1associateswithimmuneinfiltrationandferroptosisingastrointestinalcancer