Cargando…
Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma
BACKGROUND: Stomach adenocarcinoma (STAD), which accounts for approximately 95% of gastric cancer types, is a malignancy cancer with high morbidity and mortality. Tumor angiogenesis plays important roles in the progression and pathogenesis of STAD, in which long noncoding RNAs (lncRNAs) have been ve...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653638/ https://www.ncbi.nlm.nih.gov/pubmed/34876056 http://dx.doi.org/10.1186/s12885-021-08987-y |
_version_ | 1784611705100173312 |
---|---|
author | Han, Chen Zhang, Cong Wang, Huixia Li, Kexin Zhao, Lianmei |
author_facet | Han, Chen Zhang, Cong Wang, Huixia Li, Kexin Zhao, Lianmei |
author_sort | Han, Chen |
collection | PubMed |
description | BACKGROUND: Stomach adenocarcinoma (STAD), which accounts for approximately 95% of gastric cancer types, is a malignancy cancer with high morbidity and mortality. Tumor angiogenesis plays important roles in the progression and pathogenesis of STAD, in which long noncoding RNAs (lncRNAs) have been verified to be crucial for angiogenesis. Our study sought to construct a prognostic signature of angiogenesis-related lncRNAs (ARLncs) to accurately predict the survival time of STAD. METHODS: The RNA-sequencing dataset and corresponding clinical data of STAD were acquired from The Cancer Genome Atlas (TCGA). ARLnc sets were obtained from the Ensemble genome database and Molecular Signatures Database (MSigDB, Angiogenesis M14493, INTegrin pathway M160). A ARLnc-related prognostic signature was then constructed via univariate Cox and multivariate Cox regression analysis in the training cohort. Survival analysis and Cox regression were performed to assess the performance of the prognostic signature between low- and high-risk groups, which was validated in the validation cohort. Furthermore, a nomogram that combined the clinical pathological characteristics and risk score conducted to predict the overall survival (OS) of STAD. In addition, ARLnc-mRNA coexpression pairs were constructed with Pearson’s correlation analysis and visualized to infer the functional annotation of the ARLncs by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression of four ARLncs in STAD and their correlation with the angiogenesis markers, CD34 and CD105, were also validated by RT–qPCR in a clinical cohort. RESULTS: A prognostic prediction signature including four ARLncs (PVT1, LINC01315, AC245041.1, and AC037198.1) was identified and constructed. The OS of patients in the high-risk group was significantly lower than that of patients in the low-risk group (p < 0.001). The values of the time-dependent area under the curve (AUC) for the ARLnc signature for 1-, 3-, and 5- year OS were 0.683, 0.739, and 0.618 in the training cohort and 0.671, 0.646, and 0.680 in the validation cohort, respectively. Univariate and multivariate Cox regression analyses indicated that the ARLnc signature was an independent prognostic factor for STAD patients (p < 0.001). Furthermore, the nomogram and calibration curve showed accurate prediction of the survival time based on the risk score. In addition, 262 mRNAs were screened for coexpression with four ARLncs, and GO analysis showed that mRNAs were mainly involved in biological processes, including angiogenesis, cell adhesion, wound healing, and extracellular matrix organization. Furthermore, correlation analysis showed that there was a positive correlation between risk score and the expression of the angiogenesis markers, CD34 and CD105, in TCGA datasets and our clinical sample cohort. CONCLUSION: Our study constructed a prognostic signature consisting of four ARLnc genes, which was closely related to the survival of STAD patients, showing high efficacy of the prognostic signature. Thus, the present study provided a novel biomarker and promising therapeutic strategy for patients with STAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08987-y. |
format | Online Article Text |
id | pubmed-8653638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86536382021-12-08 Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma Han, Chen Zhang, Cong Wang, Huixia Li, Kexin Zhao, Lianmei BMC Cancer Research BACKGROUND: Stomach adenocarcinoma (STAD), which accounts for approximately 95% of gastric cancer types, is a malignancy cancer with high morbidity and mortality. Tumor angiogenesis plays important roles in the progression and pathogenesis of STAD, in which long noncoding RNAs (lncRNAs) have been verified to be crucial for angiogenesis. Our study sought to construct a prognostic signature of angiogenesis-related lncRNAs (ARLncs) to accurately predict the survival time of STAD. METHODS: The RNA-sequencing dataset and corresponding clinical data of STAD were acquired from The Cancer Genome Atlas (TCGA). ARLnc sets were obtained from the Ensemble genome database and Molecular Signatures Database (MSigDB, Angiogenesis M14493, INTegrin pathway M160). A ARLnc-related prognostic signature was then constructed via univariate Cox and multivariate Cox regression analysis in the training cohort. Survival analysis and Cox regression were performed to assess the performance of the prognostic signature between low- and high-risk groups, which was validated in the validation cohort. Furthermore, a nomogram that combined the clinical pathological characteristics and risk score conducted to predict the overall survival (OS) of STAD. In addition, ARLnc-mRNA coexpression pairs were constructed with Pearson’s correlation analysis and visualized to infer the functional annotation of the ARLncs by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression of four ARLncs in STAD and their correlation with the angiogenesis markers, CD34 and CD105, were also validated by RT–qPCR in a clinical cohort. RESULTS: A prognostic prediction signature including four ARLncs (PVT1, LINC01315, AC245041.1, and AC037198.1) was identified and constructed. The OS of patients in the high-risk group was significantly lower than that of patients in the low-risk group (p < 0.001). The values of the time-dependent area under the curve (AUC) for the ARLnc signature for 1-, 3-, and 5- year OS were 0.683, 0.739, and 0.618 in the training cohort and 0.671, 0.646, and 0.680 in the validation cohort, respectively. Univariate and multivariate Cox regression analyses indicated that the ARLnc signature was an independent prognostic factor for STAD patients (p < 0.001). Furthermore, the nomogram and calibration curve showed accurate prediction of the survival time based on the risk score. In addition, 262 mRNAs were screened for coexpression with four ARLncs, and GO analysis showed that mRNAs were mainly involved in biological processes, including angiogenesis, cell adhesion, wound healing, and extracellular matrix organization. Furthermore, correlation analysis showed that there was a positive correlation between risk score and the expression of the angiogenesis markers, CD34 and CD105, in TCGA datasets and our clinical sample cohort. CONCLUSION: Our study constructed a prognostic signature consisting of four ARLnc genes, which was closely related to the survival of STAD patients, showing high efficacy of the prognostic signature. Thus, the present study provided a novel biomarker and promising therapeutic strategy for patients with STAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08987-y. BioMed Central 2021-12-07 /pmc/articles/PMC8653638/ /pubmed/34876056 http://dx.doi.org/10.1186/s12885-021-08987-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Han, Chen Zhang, Cong Wang, Huixia Li, Kexin Zhao, Lianmei Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma |
title | Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma |
title_full | Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma |
title_fullStr | Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma |
title_full_unstemmed | Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma |
title_short | Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma |
title_sort | angiogenesis-related lncrnas predict the prognosis signature of stomach adenocarcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653638/ https://www.ncbi.nlm.nih.gov/pubmed/34876056 http://dx.doi.org/10.1186/s12885-021-08987-y |
work_keys_str_mv | AT hanchen angiogenesisrelatedlncrnaspredicttheprognosissignatureofstomachadenocarcinoma AT zhangcong angiogenesisrelatedlncrnaspredicttheprognosissignatureofstomachadenocarcinoma AT wanghuixia angiogenesisrelatedlncrnaspredicttheprognosissignatureofstomachadenocarcinoma AT likexin angiogenesisrelatedlncrnaspredicttheprognosissignatureofstomachadenocarcinoma AT zhaolianmei angiogenesisrelatedlncrnaspredicttheprognosissignatureofstomachadenocarcinoma |