The ferroptosis-related long non-coding RNAs signature predicts biochemical recurrence and immune cell infiltration in prostate cancer

Abstract Background Findings from numerous studies have revealed that ferroptosis is closely related to tumorigenesis and immune cell infiltration. Long non-coding RNAs (lncRNAs) are reportedly involved in the progression of various cancers, including prostate cancer (PCa). This study was designed t...

Full description

Bibliographic Details
Main Authors: Chunhui Liu, Yue Gao, Jiaxuan Ni, Saisai Chen, Qiang Hu, Can Wang, Mingjin Hu, Ming Chen
Format: Article
Language:English
Published: BMC 2022-07-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-022-09876-8
_version_ 1818509798104104960
author Chunhui Liu
Yue Gao
Jiaxuan Ni
Saisai Chen
Qiang Hu
Can Wang
Mingjin Hu
Ming Chen
author_facet Chunhui Liu
Yue Gao
Jiaxuan Ni
Saisai Chen
Qiang Hu
Can Wang
Mingjin Hu
Ming Chen
author_sort Chunhui Liu
collection DOAJ
description Abstract Background Findings from numerous studies have revealed that ferroptosis is closely related to tumorigenesis and immune cell infiltration. Long non-coding RNAs (lncRNAs) are reportedly involved in the progression of various cancers, including prostate cancer (PCa). This study was designed to establish a ferroptosis-related lncRNA (frlncRNA) signature to predict PCa prognosis. Methods The frlncRNAs were identified by studying their expression by Pearson’s correlation analysis. Differentially expressed prognosis related frlncRNAs were identified by the Wilcoxon test and univariate Cox regression analysis. The LASSO Cox regression model was used to build a model to predict biochemical recurrence (BCR) based on frlncRNAs. The GSEA software (version 4.1.0) was used to explore the enriched pathways in high- and low- risk groups. Patients with PCa were clustered into different subgroups by unsupervised clustering based on the frlncRNAs considered in the prognostic model. Real-time PCR and CCK8 assays were performed to verify the expression and function of frlncRNAs. Results We identified 35 differentially expressed prognosis related frlncRNAs based on data on PCa from TCGA. A risk signature based on five frlncRNAs (AP006284.1, AC132938.1, BCRP3, AL360181.4 and AL135999.1), was confirmed to perform well in predicting BCR. The high-risk group had higher disease grades and a greater number of infiltrating immune cells. Besides this, we found that the five frlncRNAs were connected with typical immune checkpoints. With respect to molecular mechanisms, several metabolic pathways were found to enriched in the low-risk group. Furthermore, patients could be classified into different subtypes with different PSA-free times using the five frlncRNAs. Notably, AP006284.1, AC132938.1, BCRP3 and AL135999.1 were upregulated in PCa cells and tissues, whereas AL360181.4 exhibited the opposite trend. The downregulation of BCRP3 and AP006284.1 impaired the proliferation of 22RV1 cells. Conclusion We generated a prognostic model based on five frlncRNAs, with clinical usefulness, and thus provided a novel strategy for predicting the BCR of patients with PCa.
first_indexed 2024-12-10T22:50:22Z
format Article
id doaj.art-4ddcb1b4d84e423da93d45cc65b5ad10
institution Directory Open Access Journal
issn 1471-2407
language English
last_indexed 2024-12-10T22:50:22Z
publishDate 2022-07-01
publisher BMC
record_format Article
series BMC Cancer
spelling doaj.art-4ddcb1b4d84e423da93d45cc65b5ad102022-12-22T01:30:27ZengBMCBMC Cancer1471-24072022-07-0122111410.1186/s12885-022-09876-8The ferroptosis-related long non-coding RNAs signature predicts biochemical recurrence and immune cell infiltration in prostate cancerChunhui Liu0Yue Gao1Jiaxuan Ni2Saisai Chen3Qiang Hu4Can Wang5Mingjin Hu6Ming Chen7Department of Urology, Affiliated Zhongda Hospital of Southeast UniversitySurgical Research Center, Institute of Urology, Medical School of Southeast UniversityDepartment of Urology, Affiliated Zhongda Hospital of Southeast UniversitySurgical Research Center, Institute of Urology, Medical School of Southeast UniversitySurgical Research Center, Institute of Urology, Medical School of Southeast UniversitySurgical Research Center, Institute of Urology, Medical School of Southeast UniversityDepartment of Urology, Lishui People’s HospitalDepartment of Urology, Affiliated Zhongda Hospital of Southeast UniversityAbstract Background Findings from numerous studies have revealed that ferroptosis is closely related to tumorigenesis and immune cell infiltration. Long non-coding RNAs (lncRNAs) are reportedly involved in the progression of various cancers, including prostate cancer (PCa). This study was designed to establish a ferroptosis-related lncRNA (frlncRNA) signature to predict PCa prognosis. Methods The frlncRNAs were identified by studying their expression by Pearson’s correlation analysis. Differentially expressed prognosis related frlncRNAs were identified by the Wilcoxon test and univariate Cox regression analysis. The LASSO Cox regression model was used to build a model to predict biochemical recurrence (BCR) based on frlncRNAs. The GSEA software (version 4.1.0) was used to explore the enriched pathways in high- and low- risk groups. Patients with PCa were clustered into different subgroups by unsupervised clustering based on the frlncRNAs considered in the prognostic model. Real-time PCR and CCK8 assays were performed to verify the expression and function of frlncRNAs. Results We identified 35 differentially expressed prognosis related frlncRNAs based on data on PCa from TCGA. A risk signature based on five frlncRNAs (AP006284.1, AC132938.1, BCRP3, AL360181.4 and AL135999.1), was confirmed to perform well in predicting BCR. The high-risk group had higher disease grades and a greater number of infiltrating immune cells. Besides this, we found that the five frlncRNAs were connected with typical immune checkpoints. With respect to molecular mechanisms, several metabolic pathways were found to enriched in the low-risk group. Furthermore, patients could be classified into different subtypes with different PSA-free times using the five frlncRNAs. Notably, AP006284.1, AC132938.1, BCRP3 and AL135999.1 were upregulated in PCa cells and tissues, whereas AL360181.4 exhibited the opposite trend. The downregulation of BCRP3 and AP006284.1 impaired the proliferation of 22RV1 cells. Conclusion We generated a prognostic model based on five frlncRNAs, with clinical usefulness, and thus provided a novel strategy for predicting the BCR of patients with PCa.https://doi.org/10.1186/s12885-022-09876-8FerroptosislncRNAImmune cell infiltrationProstate cancerPrognostic model
spellingShingle Chunhui Liu
Yue Gao
Jiaxuan Ni
Saisai Chen
Qiang Hu
Can Wang
Mingjin Hu
Ming Chen
The ferroptosis-related long non-coding RNAs signature predicts biochemical recurrence and immune cell infiltration in prostate cancer
BMC Cancer
Ferroptosis
lncRNA
Immune cell infiltration
Prostate cancer
Prognostic model
title The ferroptosis-related long non-coding RNAs signature predicts biochemical recurrence and immune cell infiltration in prostate cancer
title_full The ferroptosis-related long non-coding RNAs signature predicts biochemical recurrence and immune cell infiltration in prostate cancer
title_fullStr The ferroptosis-related long non-coding RNAs signature predicts biochemical recurrence and immune cell infiltration in prostate cancer
title_full_unstemmed The ferroptosis-related long non-coding RNAs signature predicts biochemical recurrence and immune cell infiltration in prostate cancer
title_short The ferroptosis-related long non-coding RNAs signature predicts biochemical recurrence and immune cell infiltration in prostate cancer
title_sort ferroptosis related long non coding rnas signature predicts biochemical recurrence and immune cell infiltration in prostate cancer
topic Ferroptosis
lncRNA
Immune cell infiltration
Prostate cancer
Prognostic model
url https://doi.org/10.1186/s12885-022-09876-8
work_keys_str_mv AT chunhuiliu theferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT yuegao theferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT jiaxuanni theferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT saisaichen theferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT qianghu theferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT canwang theferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT mingjinhu theferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT mingchen theferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT chunhuiliu ferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT yuegao ferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT jiaxuanni ferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT saisaichen ferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT qianghu ferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT canwang ferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT mingjinhu ferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer
AT mingchen ferroptosisrelatedlongnoncodingrnassignaturepredictsbiochemicalrecurrenceandimmunecellinfiltrationinprostatecancer