Cargando…
Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma
BACKGROUND: MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs d...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135252/ https://www.ncbi.nlm.nih.gov/pubmed/32251457 http://dx.doi.org/10.1371/journal.pone.0231116 |
_version_ | 1783518013721411584 |
---|---|
author | Ibuki, Yuta Nishiyama, Yukie Tsutani, Yasuhiro Emi, Manabu Hamai, Yoichi Okada, Morihito Tahara, Hidetoshi |
author_facet | Ibuki, Yuta Nishiyama, Yukie Tsutani, Yasuhiro Emi, Manabu Hamai, Yoichi Okada, Morihito Tahara, Hidetoshi |
author_sort | Ibuki, Yuta |
collection | PubMed |
description | BACKGROUND: MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer. METHODS: Serum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high‐grade dysplasia (HGD). RESULTS: Twenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3±8.9 vs. 3.1±1.3, p<0.001). The area under the receiver operating characteristics (ROC) curves of the panel index was 0.95. Sensitivity and specificity were 93.8%, and 81% in the 1st and 2nd groups, and 88.9% and 72.3% in the 3rd group, respectively. The panel index was significantly lower in patients with EAD (6.2±4.5) and HGD (4.2±1.7) than in those with ESCC and was significantly decreased at post-treatment compared with pre-treatment (6.2±5.6 vs 11.6±11.5, p = 0.03). CONCLUSION: Our diagnostic panel had high accuracy in the diagnosis of ESCC. MiR/isomiRs detected by NGS could serve as novel biomarkers of ESCC. |
format | Online Article Text |
id | pubmed-7135252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-71352522020-04-09 Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma Ibuki, Yuta Nishiyama, Yukie Tsutani, Yasuhiro Emi, Manabu Hamai, Yoichi Okada, Morihito Tahara, Hidetoshi PLoS One Research Article BACKGROUND: MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer. METHODS: Serum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high‐grade dysplasia (HGD). RESULTS: Twenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3±8.9 vs. 3.1±1.3, p<0.001). The area under the receiver operating characteristics (ROC) curves of the panel index was 0.95. Sensitivity and specificity were 93.8%, and 81% in the 1st and 2nd groups, and 88.9% and 72.3% in the 3rd group, respectively. The panel index was significantly lower in patients with EAD (6.2±4.5) and HGD (4.2±1.7) than in those with ESCC and was significantly decreased at post-treatment compared with pre-treatment (6.2±5.6 vs 11.6±11.5, p = 0.03). CONCLUSION: Our diagnostic panel had high accuracy in the diagnosis of ESCC. MiR/isomiRs detected by NGS could serve as novel biomarkers of ESCC. Public Library of Science 2020-04-06 /pmc/articles/PMC7135252/ /pubmed/32251457 http://dx.doi.org/10.1371/journal.pone.0231116 Text en © 2020 Ibuki et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ibuki, Yuta Nishiyama, Yukie Tsutani, Yasuhiro Emi, Manabu Hamai, Yoichi Okada, Morihito Tahara, Hidetoshi Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma |
title | Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma |
title_full | Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma |
title_fullStr | Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma |
title_full_unstemmed | Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma |
title_short | Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma |
title_sort | circulating microrna/isomirs as novel biomarkers of esophageal squamous cell carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135252/ https://www.ncbi.nlm.nih.gov/pubmed/32251457 http://dx.doi.org/10.1371/journal.pone.0231116 |
work_keys_str_mv | AT ibukiyuta circulatingmicrornaisomirsasnovelbiomarkersofesophagealsquamouscellcarcinoma AT nishiyamayukie circulatingmicrornaisomirsasnovelbiomarkersofesophagealsquamouscellcarcinoma AT tsutaniyasuhiro circulatingmicrornaisomirsasnovelbiomarkersofesophagealsquamouscellcarcinoma AT emimanabu circulatingmicrornaisomirsasnovelbiomarkersofesophagealsquamouscellcarcinoma AT hamaiyoichi circulatingmicrornaisomirsasnovelbiomarkersofesophagealsquamouscellcarcinoma AT okadamorihito circulatingmicrornaisomirsasnovelbiomarkersofesophagealsquamouscellcarcinoma AT taharahidetoshi circulatingmicrornaisomirsasnovelbiomarkersofesophagealsquamouscellcarcinoma |