A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis. Cuproptosis is a novel type of cell death, which differs from previously reported types of cell death such as apoptosis, autophagy, proptosis, ferroptosis, necroptosis, etc. Long non-coding RNAs (lncRNAs) play multip...

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Main Authors: Jingyi Wu, Jianzuo Yao, Shu Jia, Xiaokun Yao, Jingping Shao, Weijuan Cao, Shuwei Ma, Xiaomin Yao, Hong Li
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S240584402306560X
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author Jingyi Wu
Jianzuo Yao
Shu Jia
Xiaokun Yao
Jingping Shao
Weijuan Cao
Shuwei Ma
Xiaomin Yao
Hong Li
author_facet Jingyi Wu
Jianzuo Yao
Shu Jia
Xiaokun Yao
Jingping Shao
Weijuan Cao
Shuwei Ma
Xiaomin Yao
Hong Li
author_sort Jingyi Wu
collection DOAJ
description Background: Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis. Cuproptosis is a novel type of cell death, which differs from previously reported types of cell death such as apoptosis, autophagy, proptosis, ferroptosis, necroptosis, etc. Long non-coding RNAs (lncRNAs) play multiple roles in HCC. Methods: We downloaded information from The Cancer Genome Atlas (TCGA) database, and obtained cuproptosis-related genes from published studies. The cuproptosis-related lncRNAs were obtained by correlation analysis, and subsequently used to construct a prognostic cuproptosis-related lncRNA signature. Analyses of overall survival (OS), progression-free survival (PFS), receiver operating characteristic (ROC) curve with the area under the curve (AUC) values and the index of concordance (c-index) curve were used to evaluate the signature. The tumor microenvironment (TME) was analyzed by ESTIMATE algorithm. The immune cell data was downloaded from the Tumor Immune Estimation Resource (TIMER) 2.0 database. Immune-related pathways were analyzed by single-sample gene set enrichment analysis (ssGSEA) algorithm. Immunophenoscore (IPS) scores from The Cancer Immunome (TCIA) database were used to evaluate immunotherapy response. The “pRRophetic” was employed to screen drugs for high-risk patients. The candidate lncRNA expression levels were detected by Real Time Quantitative PCR. Results: We constructed a cuproptosis-related lncRNA signature containing seven lncRNAs: AC125437.1, PCED1B-AS1, PICSAR, AP001372.2, AC027097.1, LINC00479, and SLC6A1-AS1. This signature had excellent accuracy, and was independent of the stratification of clinicopathological features. Further study showed that high-risk tumors under this signature had higher TMB, fewer TME components and higher tumor purity. The tumors with high risk were not enriched in immune cell infiltration or immune process pathways, and high-risk patients had a poor response to immunotherapy. Moreover, 29 drugs such as sorafenib, dasatinib and paclitaxel were screened for high-risk HCC patients to improve their prognosis. The expression levels of the candidate lncRNAs in HCC tissue were significantly increased (except PCED1B-AS1). Conclusions: Our prognostic cuproptosis-related lncRNA signature was accurate and effective for predicting the prognosis of HCC. The immunotherapy was unsuitable for high-risk HCC patients with this signature.
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spelling doaj.art-6baddc86534c4f678121798ff89f00a72023-10-01T05:59:17ZengElsevierHeliyon2405-84402023-09-0199e19352A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinomaJingyi Wu0Jianzuo Yao1Shu Jia2Xiaokun Yao3Jingping Shao4Weijuan Cao5Shuwei Ma6Xiaomin Yao7Hong Li8Faculty of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, 315100, PR ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Li Huili Hospital Affiliated to Ningbo University, Ningbo, 315040, PR ChinaFaculty of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, 315100, PR ChinaFaculty of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, 315100, PR ChinaFaculty of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, 315100, PR ChinaFaculty of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, 315100, PR ChinaFaculty of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, 315100, PR ChinaFaculty of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, 315100, PR ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Li Huili Hospital Affiliated to Ningbo University, Ningbo, 315040, PR China; Corresponding author.Background: Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis. Cuproptosis is a novel type of cell death, which differs from previously reported types of cell death such as apoptosis, autophagy, proptosis, ferroptosis, necroptosis, etc. Long non-coding RNAs (lncRNAs) play multiple roles in HCC. Methods: We downloaded information from The Cancer Genome Atlas (TCGA) database, and obtained cuproptosis-related genes from published studies. The cuproptosis-related lncRNAs were obtained by correlation analysis, and subsequently used to construct a prognostic cuproptosis-related lncRNA signature. Analyses of overall survival (OS), progression-free survival (PFS), receiver operating characteristic (ROC) curve with the area under the curve (AUC) values and the index of concordance (c-index) curve were used to evaluate the signature. The tumor microenvironment (TME) was analyzed by ESTIMATE algorithm. The immune cell data was downloaded from the Tumor Immune Estimation Resource (TIMER) 2.0 database. Immune-related pathways were analyzed by single-sample gene set enrichment analysis (ssGSEA) algorithm. Immunophenoscore (IPS) scores from The Cancer Immunome (TCIA) database were used to evaluate immunotherapy response. The “pRRophetic” was employed to screen drugs for high-risk patients. The candidate lncRNA expression levels were detected by Real Time Quantitative PCR. Results: We constructed a cuproptosis-related lncRNA signature containing seven lncRNAs: AC125437.1, PCED1B-AS1, PICSAR, AP001372.2, AC027097.1, LINC00479, and SLC6A1-AS1. This signature had excellent accuracy, and was independent of the stratification of clinicopathological features. Further study showed that high-risk tumors under this signature had higher TMB, fewer TME components and higher tumor purity. The tumors with high risk were not enriched in immune cell infiltration or immune process pathways, and high-risk patients had a poor response to immunotherapy. Moreover, 29 drugs such as sorafenib, dasatinib and paclitaxel were screened for high-risk HCC patients to improve their prognosis. The expression levels of the candidate lncRNAs in HCC tissue were significantly increased (except PCED1B-AS1). Conclusions: Our prognostic cuproptosis-related lncRNA signature was accurate and effective for predicting the prognosis of HCC. The immunotherapy was unsuitable for high-risk HCC patients with this signature.http://www.sciencedirect.com/science/article/pii/S240584402306560XBioinformaticscuproptosislncRNAHepatocellular carcinomaImmunotherapy
spellingShingle Jingyi Wu
Jianzuo Yao
Shu Jia
Xiaokun Yao
Jingping Shao
Weijuan Cao
Shuwei Ma
Xiaomin Yao
Hong Li
A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma
Heliyon
Bioinformatics
cuproptosis
lncRNA
Hepatocellular carcinoma
Immunotherapy
title A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma
title_full A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma
title_fullStr A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma
title_full_unstemmed A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma
title_short A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma
title_sort cuproptosis related lncrna signature for predicting prognosis and immune response in hepatocellular carcinoma
topic Bioinformatics
cuproptosis
lncRNA
Hepatocellular carcinoma
Immunotherapy
url http://www.sciencedirect.com/science/article/pii/S240584402306560X
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