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Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability
Microsatellite instability (MSI) is an important diagnostic and prognostic cancer biomarker. In colorectal, cervical, ovarian, and gastric cancers, it can guide the prescription of chemotherapy and immunotherapy. In laboratory diagnostics of susceptible tumors, MSI is routinely detected by the size...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650122/ https://www.ncbi.nlm.nih.gov/pubmed/34888350 http://dx.doi.org/10.3389/fmolb.2021.737821 |
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author | Sorokin, Maksim Rabushko, Elizaveta Efimov, Victor Poddubskaya, Elena Sekacheva, Marina Simonov, Alexander Nikitin, Daniil Drobyshev, Aleksey Suntsova, Maria Buzdin, Anton |
author_facet | Sorokin, Maksim Rabushko, Elizaveta Efimov, Victor Poddubskaya, Elena Sekacheva, Marina Simonov, Alexander Nikitin, Daniil Drobyshev, Aleksey Suntsova, Maria Buzdin, Anton |
author_sort | Sorokin, Maksim |
collection | PubMed |
description | Microsatellite instability (MSI) is an important diagnostic and prognostic cancer biomarker. In colorectal, cervical, ovarian, and gastric cancers, it can guide the prescription of chemotherapy and immunotherapy. In laboratory diagnostics of susceptible tumors, MSI is routinely detected by the size of marker polymerase chain reaction products encompassing frequent microsatellite expansion regions. Alternatively, MSI status is screened indirectly by immunohistochemical interrogation of microsatellite binding proteins. RNA sequencing (RNAseq) profiling is an emerging source of data for a wide spectrum of cancer biomarkers. Recently, three RNAseq-based gene signatures were deduced for establishing MSI status in tumor samples. They had 25, 15, and 14 gene products with only one common gene. However, they were developed and tested on the incomplete literature of The Cancer Genome Atlas (TCGA) sampling and never validated experimentally on independent RNAseq samples. In this study, we, for the first time, systematically validated these three RNAseq MSI signatures on the literature colorectal cancer (CRC) (n = 619), endometrial carcinoma (n = 533), gastric cancer (n = 380), uterine carcinosarcoma (n = 55), and esophageal cancer (n = 83) samples and on the set of experimental CRC RNAseq samples (n = 23) for tumors with known MSI status. We found that all three signatures performed well with area under the curve (AUC) ranges of 0.94–1 for the experimental CRCs and 0.94–1 for the TCGA CRC, esophageal cancer, and uterine carcinosarcoma samples. However, for the TCGA endometrial carcinoma and gastric cancer samples, only two signatures were effective with AUC 0.91–0.97, whereas the third signature showed a significantly lower AUC of 0.69–0.88. Software for calculating these MSI signatures using RNAseq data is included. |
format | Online Article Text |
id | pubmed-8650122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86501222021-12-08 Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability Sorokin, Maksim Rabushko, Elizaveta Efimov, Victor Poddubskaya, Elena Sekacheva, Marina Simonov, Alexander Nikitin, Daniil Drobyshev, Aleksey Suntsova, Maria Buzdin, Anton Front Mol Biosci Molecular Biosciences Microsatellite instability (MSI) is an important diagnostic and prognostic cancer biomarker. In colorectal, cervical, ovarian, and gastric cancers, it can guide the prescription of chemotherapy and immunotherapy. In laboratory diagnostics of susceptible tumors, MSI is routinely detected by the size of marker polymerase chain reaction products encompassing frequent microsatellite expansion regions. Alternatively, MSI status is screened indirectly by immunohistochemical interrogation of microsatellite binding proteins. RNA sequencing (RNAseq) profiling is an emerging source of data for a wide spectrum of cancer biomarkers. Recently, three RNAseq-based gene signatures were deduced for establishing MSI status in tumor samples. They had 25, 15, and 14 gene products with only one common gene. However, they were developed and tested on the incomplete literature of The Cancer Genome Atlas (TCGA) sampling and never validated experimentally on independent RNAseq samples. In this study, we, for the first time, systematically validated these three RNAseq MSI signatures on the literature colorectal cancer (CRC) (n = 619), endometrial carcinoma (n = 533), gastric cancer (n = 380), uterine carcinosarcoma (n = 55), and esophageal cancer (n = 83) samples and on the set of experimental CRC RNAseq samples (n = 23) for tumors with known MSI status. We found that all three signatures performed well with area under the curve (AUC) ranges of 0.94–1 for the experimental CRCs and 0.94–1 for the TCGA CRC, esophageal cancer, and uterine carcinosarcoma samples. However, for the TCGA endometrial carcinoma and gastric cancer samples, only two signatures were effective with AUC 0.91–0.97, whereas the third signature showed a significantly lower AUC of 0.69–0.88. Software for calculating these MSI signatures using RNAseq data is included. Frontiers Media S.A. 2021-11-23 /pmc/articles/PMC8650122/ /pubmed/34888350 http://dx.doi.org/10.3389/fmolb.2021.737821 Text en Copyright © 2021 Sorokin, Rabushko, Efimov, Poddubskaya, Sekacheva, Simonov, Nikitin, Drobyshev, Suntsova and Buzdin. 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 | Molecular Biosciences Sorokin, Maksim Rabushko, Elizaveta Efimov, Victor Poddubskaya, Elena Sekacheva, Marina Simonov, Alexander Nikitin, Daniil Drobyshev, Aleksey Suntsova, Maria Buzdin, Anton Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability |
title | Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability |
title_full | Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability |
title_fullStr | Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability |
title_full_unstemmed | Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability |
title_short | Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability |
title_sort | experimental and meta-analytic validation of rna sequencing signatures for predicting status of microsatellite instability |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650122/ https://www.ncbi.nlm.nih.gov/pubmed/34888350 http://dx.doi.org/10.3389/fmolb.2021.737821 |
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