Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma

Abstract Long non-coding RNAs (lncRNAs) have a notable role in the diagnosis and prognosis of cancer. However, the associations between lncRNA-related hub genes (LRHGs) expression and the corresponding outcomes have not been fully understood in lung adenocarcinoma (LUAD). Here, a total of 71 patient...

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Main Authors: Yong Li, Danfei Shi, Yan Jiang, Yanqin Hu, Qiuxia Liu, Yanping Xie, Xilin Zhang
Format: Article
Language:English
Published: BMC 2024-11-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-024-13144-2
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author Yong Li
Danfei Shi
Yan Jiang
Yanqin Hu
Qiuxia Liu
Yanping Xie
Xilin Zhang
author_facet Yong Li
Danfei Shi
Yan Jiang
Yanqin Hu
Qiuxia Liu
Yanping Xie
Xilin Zhang
author_sort Yong Li
collection DOAJ
description Abstract Long non-coding RNAs (lncRNAs) have a notable role in the diagnosis and prognosis of cancer. However, the associations between lncRNA-related hub genes (LRHGs) expression and the corresponding outcomes have not been fully understood in lung adenocarcinoma (LUAD). Here, a total of 71 patients diagnosed with LUAD and 60 healthy volunteers at The First Affiliated Hospital of Huzhou University from April, 2023 to December, 2023 were enrolled in the present study. A LRHGs model was established using least absolute shrinkage and selection operator analyses of The Cancer Genome Atlas-LUAD datasets. The underlying mechanisms of the LRHGs were investigated via Gene Set Enrichment Analysis and Gene Set Variation Analysis. Additionally, the diagnostic role of serum HOXD cluster antisense RNA 2 (HOXD-AS2) was assessed by receiver operating characteristic (ROC) curve analysis. Lastly, TCGA-LUAD samples were divided into high- and low-HOXD-AS2 expression groups based on the median expression. The associations between HOXD-AS2 expression and miR-4538 as well as Calmodulin-Dependent Protein Kinase Type II subunit Beta (CAMK2B) levels were conducted through Pearson correlation analysis. A comprehensive analysis identified 141 differentially expressed lncRNAs between 539 LUAD tissues and 59 normal samples. A prognostic marker for overall survival was established by constructing a predictive signature consisting of 9 LRHGs. Subsequently, 474 LUAD samples were categorized into a high or low-risk group based on the median of the risk score. An independent prognostic model was constructed to confirm the validity of this categorization. Further comparisons of the clinicopathological features and LRHG-related pathways were performed between the two groups. Examinations of LRHG expression in two LUAD clusters and of the association between LRHG expression and immune infiltration were also conducted. HOXD-AS2 expression was shown to be elevated in LUAD tissues compared with matched normal tissues, and the serum HOXD-AS2 level was also notably increased in LUAD samples compared with healthy controls. The results of the ROC analysis indicated that the sensitivity and specificity of HOXD-AS2 were higher than that of cytokeratin-19 fragment (CYFRA21-1), which is a serum marker for LUAD. Pearson analyses indicated that miR-4538 level was negatively associated with HOXD-AS2 expression, but CAMK2B level showed positive correlation in LUAD. The results of the present study therefore indicated that the constructed LRHG model, particularly HOXD-AS2, could independently diagnose and predict the prognosis of LUAD, which suggested the underlying mechanism of the HOXD-AS2/miR-4538/CAMK2B, and might offer efficient strategies for LUAD treatment.
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spelling doaj-art-847be521bf244007a0b3d33c5a4d58132024-11-10T12:29:38ZengBMCBMC Cancer1471-24072024-11-0124112110.1186/s12885-024-13144-2Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinomaYong Li0Danfei Shi1Yan Jiang2Yanqin Hu3Qiuxia Liu4Yanping Xie5Xilin Zhang6Department of Laboratory Medicine, First Affiliated Hospital of Huzhou UniversityDepartment of Pathology, First Affiliated Hospital of Huzhou UniversityDepartment of Respiratory Medicine, First Affiliated Hospital of Huzhou UniversityDepartment of Laboratory Medicine, First Affiliated Hospital of Huzhou UniversityDepartment of Laboratory Medicine, First Affiliated Hospital of Huzhou UniversityDepartment of Respiratory Medicine, First Affiliated Hospital of Huzhou UniversityCentral Laboratory, Huzhou Key Laboratory of Translational Medicine, First Affiliated Hospital of Huzhou UniversityAbstract Long non-coding RNAs (lncRNAs) have a notable role in the diagnosis and prognosis of cancer. However, the associations between lncRNA-related hub genes (LRHGs) expression and the corresponding outcomes have not been fully understood in lung adenocarcinoma (LUAD). Here, a total of 71 patients diagnosed with LUAD and 60 healthy volunteers at The First Affiliated Hospital of Huzhou University from April, 2023 to December, 2023 were enrolled in the present study. A LRHGs model was established using least absolute shrinkage and selection operator analyses of The Cancer Genome Atlas-LUAD datasets. The underlying mechanisms of the LRHGs were investigated via Gene Set Enrichment Analysis and Gene Set Variation Analysis. Additionally, the diagnostic role of serum HOXD cluster antisense RNA 2 (HOXD-AS2) was assessed by receiver operating characteristic (ROC) curve analysis. Lastly, TCGA-LUAD samples were divided into high- and low-HOXD-AS2 expression groups based on the median expression. The associations between HOXD-AS2 expression and miR-4538 as well as Calmodulin-Dependent Protein Kinase Type II subunit Beta (CAMK2B) levels were conducted through Pearson correlation analysis. A comprehensive analysis identified 141 differentially expressed lncRNAs between 539 LUAD tissues and 59 normal samples. A prognostic marker for overall survival was established by constructing a predictive signature consisting of 9 LRHGs. Subsequently, 474 LUAD samples were categorized into a high or low-risk group based on the median of the risk score. An independent prognostic model was constructed to confirm the validity of this categorization. Further comparisons of the clinicopathological features and LRHG-related pathways were performed between the two groups. Examinations of LRHG expression in two LUAD clusters and of the association between LRHG expression and immune infiltration were also conducted. HOXD-AS2 expression was shown to be elevated in LUAD tissues compared with matched normal tissues, and the serum HOXD-AS2 level was also notably increased in LUAD samples compared with healthy controls. The results of the ROC analysis indicated that the sensitivity and specificity of HOXD-AS2 were higher than that of cytokeratin-19 fragment (CYFRA21-1), which is a serum marker for LUAD. Pearson analyses indicated that miR-4538 level was negatively associated with HOXD-AS2 expression, but CAMK2B level showed positive correlation in LUAD. The results of the present study therefore indicated that the constructed LRHG model, particularly HOXD-AS2, could independently diagnose and predict the prognosis of LUAD, which suggested the underlying mechanism of the HOXD-AS2/miR-4538/CAMK2B, and might offer efficient strategies for LUAD treatment.https://doi.org/10.1186/s12885-024-13144-2Lung adenocarcinomaLncRNADiagnosisceRNA
spellingShingle Yong Li
Danfei Shi
Yan Jiang
Yanqin Hu
Qiuxia Liu
Yanping Xie
Xilin Zhang
Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma
BMC Cancer
Lung adenocarcinoma
LncRNA
Diagnosis
ceRNA
title Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma
title_full Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma
title_fullStr Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma
title_full_unstemmed Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma
title_short Establishment of potential lncRNA-related hub genes involved competitive endogenous RNA in lung adenocarcinoma
title_sort establishment of potential lncrna related hub genes involved competitive endogenous rna in lung adenocarcinoma
topic Lung adenocarcinoma
LncRNA
Diagnosis
ceRNA
url https://doi.org/10.1186/s12885-024-13144-2
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AT danfeishi establishmentofpotentiallncrnarelatedhubgenesinvolvedcompetitiveendogenousrnainlungadenocarcinoma
AT yanjiang establishmentofpotentiallncrnarelatedhubgenesinvolvedcompetitiveendogenousrnainlungadenocarcinoma
AT yanqinhu establishmentofpotentiallncrnarelatedhubgenesinvolvedcompetitiveendogenousrnainlungadenocarcinoma
AT qiuxialiu establishmentofpotentiallncrnarelatedhubgenesinvolvedcompetitiveendogenousrnainlungadenocarcinoma
AT yanpingxie establishmentofpotentiallncrnarelatedhubgenesinvolvedcompetitiveendogenousrnainlungadenocarcinoma
AT xilinzhang establishmentofpotentiallncrnarelatedhubgenesinvolvedcompetitiveendogenousrnainlungadenocarcinoma