Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma

Cholangiocarcinoma (CCA) is featured by common occurrence and poor prognosis. Autophagy is a biological process that has been extensively involved in the progression of tumors. Long noncoding RNAs (lncRNAs) have been discovered to be critical in diagnosing and predicting various tumors. It may be va...

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Autores principales:	Ya Jun Liu, Alphonse Houssou Hounye, Zheng Wang, Xiaowei Liu, Jun Yi, Min Qi
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	autophagy long noncoding RNAs cholangiocarcinoma The Cancer Genome Atlas prognostic signature Gene Expression Omnibus Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ee1a26e7368644e4a1c7970c5f5d0f9f
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spelling	oai:doaj.org-article:ee1a26e7368644e4a1c7970c5f5d0f9f2021-12-02T10:13:31ZIdentification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma2234-943X10.3389/fonc.2021.780601https://doaj.org/article/ee1a26e7368644e4a1c7970c5f5d0f9f2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.780601/fullhttps://doaj.org/toc/2234-943XCholangiocarcinoma (CCA) is featured by common occurrence and poor prognosis. Autophagy is a biological process that has been extensively involved in the progression of tumors. Long noncoding RNAs (lncRNAs) have been discovered to be critical in diagnosing and predicting various tumors. It may be valuable to elaborate autophagy-related lncRNAs (ARlncRNAs) in CCA, and indeed, there are still few studies concerning the role of ARlncRNAs in CCA. Here, a prognostic ARlncRNA signature was constructed to predict the survival outcome of CCA patients. Through identification, three differentially expressed ARlncRNAs (DEARlncRNAs), including CHRM3.AS2, MIR205HG, and LINC00661, were screened and were considered predictive signatures. Furthermore, the overall survival (OS) of patients with high-risk scores was significantly lower than that of patients with low scores. Interestingly, the risk score was an independent factor for the OS of patients with CCA. Moreover, receiver operating characteristic (ROC) curve analysis showed that the screened and constructed prognosis signature for 1 year (AUC = 0.884), 3 years (AUC =0.759), and 5 years (AUC = 0.788) presented a high score of accuracy in predicting OS of CCA patients. Gene set enrichment analysis (GSEA) revealed that the three DEARlncRNAs were significantly enriched in CCA-related signaling pathways, including “pathways of basal cell carcinoma”, “glycerolipid metabolism”, etc. Quantitative real-time PCR (qRT-PCR) showed that expressions of CHRM3.AS2, MIR205HG, and LINC00661 were higher in CCA tissues than those in normal tissues, similar to the trends detected in the CCA dataset. Furthermore, Pearson’s analysis reported an intimate correlation of the risk score with immune cell infiltration, indicating a predictive value of the signature for the efficacy of immunotherapy. In addition, the screened lncRNAs were found to have the ability to modulate the expression of mRNAs by interacting with miRNAs based on the established lncRNA-miRNA-mRNA network. In conclusion, our study develops a novel nomogram with good reliability and accuracy to predict the OS of CCA patients, providing a significant guiding value for developing tailored therapy for CCA patients.Ya Jun LiuAlphonse Houssou HounyeZheng WangZheng WangXiaowei LiuJun YiMin QiFrontiers Media S.A.articleautophagylong noncoding RNAscholangiocarcinomaThe Cancer Genome Atlasprognostic signatureGene Expression OmnibusNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autophagy long noncoding RNAs cholangiocarcinoma The Cancer Genome Atlas prognostic signature Gene Expression Omnibus Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	autophagy long noncoding RNAs cholangiocarcinoma The Cancer Genome Atlas prognostic signature Gene Expression Omnibus Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ya Jun Liu Alphonse Houssou Hounye Zheng Wang Zheng Wang Xiaowei Liu Jun Yi Min Qi Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma
description	Cholangiocarcinoma (CCA) is featured by common occurrence and poor prognosis. Autophagy is a biological process that has been extensively involved in the progression of tumors. Long noncoding RNAs (lncRNAs) have been discovered to be critical in diagnosing and predicting various tumors. It may be valuable to elaborate autophagy-related lncRNAs (ARlncRNAs) in CCA, and indeed, there are still few studies concerning the role of ARlncRNAs in CCA. Here, a prognostic ARlncRNA signature was constructed to predict the survival outcome of CCA patients. Through identification, three differentially expressed ARlncRNAs (DEARlncRNAs), including CHRM3.AS2, MIR205HG, and LINC00661, were screened and were considered predictive signatures. Furthermore, the overall survival (OS) of patients with high-risk scores was significantly lower than that of patients with low scores. Interestingly, the risk score was an independent factor for the OS of patients with CCA. Moreover, receiver operating characteristic (ROC) curve analysis showed that the screened and constructed prognosis signature for 1 year (AUC = 0.884), 3 years (AUC =0.759), and 5 years (AUC = 0.788) presented a high score of accuracy in predicting OS of CCA patients. Gene set enrichment analysis (GSEA) revealed that the three DEARlncRNAs were significantly enriched in CCA-related signaling pathways, including “pathways of basal cell carcinoma”, “glycerolipid metabolism”, etc. Quantitative real-time PCR (qRT-PCR) showed that expressions of CHRM3.AS2, MIR205HG, and LINC00661 were higher in CCA tissues than those in normal tissues, similar to the trends detected in the CCA dataset. Furthermore, Pearson’s analysis reported an intimate correlation of the risk score with immune cell infiltration, indicating a predictive value of the signature for the efficacy of immunotherapy. In addition, the screened lncRNAs were found to have the ability to modulate the expression of mRNAs by interacting with miRNAs based on the established lncRNA-miRNA-mRNA network. In conclusion, our study develops a novel nomogram with good reliability and accuracy to predict the OS of CCA patients, providing a significant guiding value for developing tailored therapy for CCA patients.
format	article
author	Ya Jun Liu Alphonse Houssou Hounye Zheng Wang Zheng Wang Xiaowei Liu Jun Yi Min Qi
author_facet	Ya Jun Liu Alphonse Houssou Hounye Zheng Wang Zheng Wang Xiaowei Liu Jun Yi Min Qi
author_sort	Ya Jun Liu
title	Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma
title_short	Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma
title_full	Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma
title_fullStr	Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma
title_full_unstemmed	Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma
title_sort	identification and validation of three autophagy-related long noncoding rnas as prognostic signature in cholangiocarcinoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ee1a26e7368644e4a1c7970c5f5d0f9f
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Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma

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