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lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels
BACKGROUND: Early diagnosis of colorectal cancer could significantly improve the prognosis and reduce mortality. However, indeterminate diagnosis is often met in pathology diagnosis in biopsy samples. Abnormal expression of long non-coding RNA (lncRNA) is associated with the initiation and progressi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428707/ https://www.ncbi.nlm.nih.gov/pubmed/36059706 http://dx.doi.org/10.3389/fonc.2022.912882 |
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author | Wang, Ouxi Shi, Di Li, Yaqi Zhou, Xiaoyan Yan, Haidan Yao, Qianlan |
author_facet | Wang, Ouxi Shi, Di Li, Yaqi Zhou, Xiaoyan Yan, Haidan Yao, Qianlan |
author_sort | Wang, Ouxi |
collection | PubMed |
description | BACKGROUND: Early diagnosis of colorectal cancer could significantly improve the prognosis and reduce mortality. However, indeterminate diagnosis is often met in pathology diagnosis in biopsy samples. Abnormal expression of long non-coding RNA (lncRNA) is associated with the initiation and progression of colorectal cancer. It is of great value and clinical significance to explore lncRNAs as candidate diagnostic biomarkers in colorectal cancer. METHODS: Based on the within-sample relative expression levels of lncRNA pairs, we identified a group of candidate diagnostic biomarkers for colorectal cancer. In addition, we validated it in independent datasets produced by different laboratories and different platforms. We also tested it in colorectal cancer tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: A biomarker consisting of six lncRNA pairs including nine lncRNAs was identified for the diagnosis of colorectal cancer. For a total of 950 cancer samples and 247 non-cancer samples, both of the sensitivity and specificity could achieve approximately 90%. For adenoma samples, the accuracy could achieve 73%. For normal tissues from inflammatory bowel disease patients, 93% (14/15) were correctly classified as non-cancer. Furthermore, the lncRNA pair biomarker showed excellent performance in all clinical stages; even in the early stage, the accuracy could achieve 87% and 82% in stage I and II. Meanwhile, the biomarker was also robust to the microsatellite instability status. More importantly, we measured the biomarker in 35 colorectal cancer and 30 cancer-adjacent tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). The accuracy could achieve 93.3% (70/75). Specially, even in early-stage tumors (I and II), the accuracy could also achieve 90.9% (30/33). The enrichment analysis revealed that these lncRNAs were involved in highly associated cancer pathways and immune-related pathways. Immune analysis showed that these marker lncRNAs were associated with multiple immune cells, implying that they might be involved in the regulation of immune cell functions in colorectal cancer. Most of the biomarker lncRNAs were also differentially expressed between the mutant group and wild-type group of colorectal cancer driver genes. CONCLUSION: We identified and validated six lncRNA pairs including nine lncRNAs as a biomarker for assisting in the diagnosis of colorectal cancer. |
format | Online Article Text |
id | pubmed-9428707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94287072022-09-01 lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels Wang, Ouxi Shi, Di Li, Yaqi Zhou, Xiaoyan Yan, Haidan Yao, Qianlan Front Oncol Oncology BACKGROUND: Early diagnosis of colorectal cancer could significantly improve the prognosis and reduce mortality. However, indeterminate diagnosis is often met in pathology diagnosis in biopsy samples. Abnormal expression of long non-coding RNA (lncRNA) is associated with the initiation and progression of colorectal cancer. It is of great value and clinical significance to explore lncRNAs as candidate diagnostic biomarkers in colorectal cancer. METHODS: Based on the within-sample relative expression levels of lncRNA pairs, we identified a group of candidate diagnostic biomarkers for colorectal cancer. In addition, we validated it in independent datasets produced by different laboratories and different platforms. We also tested it in colorectal cancer tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: A biomarker consisting of six lncRNA pairs including nine lncRNAs was identified for the diagnosis of colorectal cancer. For a total of 950 cancer samples and 247 non-cancer samples, both of the sensitivity and specificity could achieve approximately 90%. For adenoma samples, the accuracy could achieve 73%. For normal tissues from inflammatory bowel disease patients, 93% (14/15) were correctly classified as non-cancer. Furthermore, the lncRNA pair biomarker showed excellent performance in all clinical stages; even in the early stage, the accuracy could achieve 87% and 82% in stage I and II. Meanwhile, the biomarker was also robust to the microsatellite instability status. More importantly, we measured the biomarker in 35 colorectal cancer and 30 cancer-adjacent tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). The accuracy could achieve 93.3% (70/75). Specially, even in early-stage tumors (I and II), the accuracy could also achieve 90.9% (30/33). The enrichment analysis revealed that these lncRNAs were involved in highly associated cancer pathways and immune-related pathways. Immune analysis showed that these marker lncRNAs were associated with multiple immune cells, implying that they might be involved in the regulation of immune cell functions in colorectal cancer. Most of the biomarker lncRNAs were also differentially expressed between the mutant group and wild-type group of colorectal cancer driver genes. CONCLUSION: We identified and validated six lncRNA pairs including nine lncRNAs as a biomarker for assisting in the diagnosis of colorectal cancer. Frontiers Media S.A. 2022-08-17 /pmc/articles/PMC9428707/ /pubmed/36059706 http://dx.doi.org/10.3389/fonc.2022.912882 Text en Copyright © 2022 Wang, Shi, Li, Zhou, Yan and Yao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Wang, Ouxi Shi, Di Li, Yaqi Zhou, Xiaoyan Yan, Haidan Yao, Qianlan lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels |
title | lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels |
title_full | lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels |
title_fullStr | lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels |
title_full_unstemmed | lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels |
title_short | lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels |
title_sort | lncrna pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428707/ https://www.ncbi.nlm.nih.gov/pubmed/36059706 http://dx.doi.org/10.3389/fonc.2022.912882 |
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