Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients

Background: Platelets (PLT) have a significant effect in promoting cancer progression and hematogenous metastasis. However, the effect of platelet activation-related lncRNAs (PLT-related lncRNAs) in gastric cancer (GC) is still poorly understood. In this study, we screened and validated PLT-related...

Full description

Bibliographic Details
Main Authors: Mingjie Yuan, Yanfei Jia, Yuanxin Xing, Yunshan Wang, Yunyun Liu, Xiangdong Liu, Duanrui Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.965033/full
_version_ 1798033290442047488
author Mingjie Yuan
Mingjie Yuan
Yanfei Jia
Yuanxin Xing
Yunshan Wang
Yunyun Liu
Yunyun Liu
Xiangdong Liu
Duanrui Liu
author_facet Mingjie Yuan
Mingjie Yuan
Yanfei Jia
Yuanxin Xing
Yunshan Wang
Yunyun Liu
Yunyun Liu
Xiangdong Liu
Duanrui Liu
author_sort Mingjie Yuan
collection DOAJ
description Background: Platelets (PLT) have a significant effect in promoting cancer progression and hematogenous metastasis. However, the effect of platelet activation-related lncRNAs (PLT-related lncRNAs) in gastric cancer (GC) is still poorly understood. In this study, we screened and validated PLT-related lncRNAs as potential biomarkers for prognosis and immunotherapy in GC patients.Methods: We obtained relevant datasets from the Cancer Genome Atlas (TCGA) and Gene Ontology (GO) Resource Database. Pearson correlation analysis was used to identify PLT-related lncRNAs. By using the univariate, least absolute shrinkage and selection operator (LASSO) Cox regression analyses, we constructed the PLT-related lncRNAs model. Kaplan-Meier survival analysis, univariate, multivariate Cox regression analysis, and nomogram were used to verify the model. The Gene Set Enrichment Analysis (GSEA), drug screening, tumor immune microenvironment analysis, epithelial-mesenchymal transition (EMT), and DNA methylation regulators correlation analysis were performed in the high- and low-risk groups. Patients were regrouped based on the risk model, and candidate compounds and immunotherapeutic responses aimed at GC subgroups were also identified. The expression of seven PLT-related lncRNAs was validated in clinical medical samples using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: In this study, a risk prediction model was established using seven PLT-related lncRNAs -(AL355574.1, LINC01697, AC002401.4, AC129507.1, AL513123.1, LINC01094, and AL356417.2), whose expression were validated in GC patients. Kaplan-Meier survival analysis, the receiver operating characteristic (ROC) curve analysis, univariate, multivariate Cox regression analysis verified the accuracy of the model. We screened multiple targeted drugs for the high-risk patients. Patients in the high-risk group had a poorer prognosis since low infiltration of immune killer cells, activation of immunosuppressive pathways, and poor response to immunotherapy. In addition, we revealed a close relationship between risk scores and EMT and DNA methylation regulators. The nomogram based on risk score suggested a good ability to predict prognosis and high clinical benefits.Conclusion: Our findings provide new insights into how PLT-related lncRNAs biomarkers affect prognosis and immunotherapy. Also, these lncRNAs may become potential biomarkers and therapeutic targets for GC patients.
first_indexed 2024-04-11T20:27:56Z
format Article
id doaj.art-31e2159f420842debadd2c7f829e925a
institution Directory Open Access Journal
issn 1664-8021
language English
last_indexed 2024-04-11T20:27:56Z
publishDate 2022-09-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Genetics
spelling doaj.art-31e2159f420842debadd2c7f829e925a2022-12-22T04:04:36ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.965033965033Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patientsMingjie Yuan0Mingjie Yuan1Yanfei Jia2Yuanxin Xing3Yunshan Wang4Yunyun Liu5Yunyun Liu6Xiangdong Liu7Duanrui Liu8Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Laboratory, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, ChinaResearch Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, ChinaResearch Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, ChinaResearch Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, ChinaResearch Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, ChinaResearch Center of Basic Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaBackground: Platelets (PLT) have a significant effect in promoting cancer progression and hematogenous metastasis. However, the effect of platelet activation-related lncRNAs (PLT-related lncRNAs) in gastric cancer (GC) is still poorly understood. In this study, we screened and validated PLT-related lncRNAs as potential biomarkers for prognosis and immunotherapy in GC patients.Methods: We obtained relevant datasets from the Cancer Genome Atlas (TCGA) and Gene Ontology (GO) Resource Database. Pearson correlation analysis was used to identify PLT-related lncRNAs. By using the univariate, least absolute shrinkage and selection operator (LASSO) Cox regression analyses, we constructed the PLT-related lncRNAs model. Kaplan-Meier survival analysis, univariate, multivariate Cox regression analysis, and nomogram were used to verify the model. The Gene Set Enrichment Analysis (GSEA), drug screening, tumor immune microenvironment analysis, epithelial-mesenchymal transition (EMT), and DNA methylation regulators correlation analysis were performed in the high- and low-risk groups. Patients were regrouped based on the risk model, and candidate compounds and immunotherapeutic responses aimed at GC subgroups were also identified. The expression of seven PLT-related lncRNAs was validated in clinical medical samples using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: In this study, a risk prediction model was established using seven PLT-related lncRNAs -(AL355574.1, LINC01697, AC002401.4, AC129507.1, AL513123.1, LINC01094, and AL356417.2), whose expression were validated in GC patients. Kaplan-Meier survival analysis, the receiver operating characteristic (ROC) curve analysis, univariate, multivariate Cox regression analysis verified the accuracy of the model. We screened multiple targeted drugs for the high-risk patients. Patients in the high-risk group had a poorer prognosis since low infiltration of immune killer cells, activation of immunosuppressive pathways, and poor response to immunotherapy. In addition, we revealed a close relationship between risk scores and EMT and DNA methylation regulators. The nomogram based on risk score suggested a good ability to predict prognosis and high clinical benefits.Conclusion: Our findings provide new insights into how PLT-related lncRNAs biomarkers affect prognosis and immunotherapy. Also, these lncRNAs may become potential biomarkers and therapeutic targets for GC patients.https://www.frontiersin.org/articles/10.3389/fgene.2022.965033/fullgastric cancerimmunotherapyplateletlncRNAprognosis
spellingShingle Mingjie Yuan
Mingjie Yuan
Yanfei Jia
Yuanxin Xing
Yunshan Wang
Yunyun Liu
Yunyun Liu
Xiangdong Liu
Duanrui Liu
Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients
Frontiers in Genetics
gastric cancer
immunotherapy
platelet
lncRNA
prognosis
title Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients
title_full Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients
title_fullStr Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients
title_full_unstemmed Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients
title_short Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients
title_sort screening and validation of platelet activation related lncrnas as potential biomarkers for prognosis and immunotherapy in gastric cancer patients
topic gastric cancer
immunotherapy
platelet
lncRNA
prognosis
url https://www.frontiersin.org/articles/10.3389/fgene.2022.965033/full
work_keys_str_mv AT mingjieyuan screeningandvalidationofplateletactivationrelatedlncrnasaspotentialbiomarkersforprognosisandimmunotherapyingastriccancerpatients
AT mingjieyuan screeningandvalidationofplateletactivationrelatedlncrnasaspotentialbiomarkersforprognosisandimmunotherapyingastriccancerpatients
AT yanfeijia screeningandvalidationofplateletactivationrelatedlncrnasaspotentialbiomarkersforprognosisandimmunotherapyingastriccancerpatients
AT yuanxinxing screeningandvalidationofplateletactivationrelatedlncrnasaspotentialbiomarkersforprognosisandimmunotherapyingastriccancerpatients
AT yunshanwang screeningandvalidationofplateletactivationrelatedlncrnasaspotentialbiomarkersforprognosisandimmunotherapyingastriccancerpatients
AT yunyunliu screeningandvalidationofplateletactivationrelatedlncrnasaspotentialbiomarkersforprognosisandimmunotherapyingastriccancerpatients
AT yunyunliu screeningandvalidationofplateletactivationrelatedlncrnasaspotentialbiomarkersforprognosisandimmunotherapyingastriccancerpatients
AT xiangdongliu screeningandvalidationofplateletactivationrelatedlncrnasaspotentialbiomarkersforprognosisandimmunotherapyingastriccancerpatients
AT duanruiliu screeningandvalidationofplateletactivationrelatedlncrnasaspotentialbiomarkersforprognosisandimmunotherapyingastriccancerpatients