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...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:acc6c406b73b4c85a65a3ca797d6170a2021-11-30T12:53:56ZExperimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability2296-889X10.3389/fmolb.2021.737821https://doaj.org/article/acc6c406b73b4c85a65a3ca797d6170a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.737821/fullhttps://doaj.org/toc/2296-889XMicrosatellite 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.Maksim SorokinMaksim SorokinMaksim SorokinElizaveta RabushkoElizaveta RabushkoVictor EfimovVictor EfimovVictor EfimovElena PoddubskayaMarina SekachevaAlexander SimonovAlexander SimonovDaniil NikitinDaniil NikitinAleksey DrobyshevMaria SuntsovaMaria SuntsovaAnton BuzdinAnton BuzdinAnton BuzdinAnton BuzdinFrontiers Media S.A.articlemicrosatellite instabilityRNA sequencingNGSRNAseqgene signaturesexperimental validationBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021) |
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microsatellite instability RNA sequencing NGS RNAseq gene signatures experimental validation Biology (General) QH301-705.5 |
| spellingShingle |
microsatellite instability RNA sequencing NGS RNAseq gene signatures experimental validation Biology (General) QH301-705.5 Maksim Sorokin Maksim Sorokin Maksim Sorokin Elizaveta Rabushko Elizaveta Rabushko Victor Efimov Victor Efimov Victor Efimov Elena Poddubskaya Marina Sekacheva Alexander Simonov Alexander Simonov Daniil Nikitin Daniil Nikitin Aleksey Drobyshev Maria Suntsova Maria Suntsova Anton Buzdin Anton Buzdin Anton Buzdin Anton Buzdin Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability |
| 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 |
article |
| author |
Maksim Sorokin Maksim Sorokin Maksim Sorokin Elizaveta Rabushko Elizaveta Rabushko Victor Efimov Victor Efimov Victor Efimov Elena Poddubskaya Marina Sekacheva Alexander Simonov Alexander Simonov Daniil Nikitin Daniil Nikitin Aleksey Drobyshev Maria Suntsova Maria Suntsova Anton Buzdin Anton Buzdin Anton Buzdin Anton Buzdin |
| author_facet |
Maksim Sorokin Maksim Sorokin Maksim Sorokin Elizaveta Rabushko Elizaveta Rabushko Victor Efimov Victor Efimov Victor Efimov Elena Poddubskaya Marina Sekacheva Alexander Simonov Alexander Simonov Daniil Nikitin Daniil Nikitin Aleksey Drobyshev Maria Suntsova Maria Suntsova Anton Buzdin Anton Buzdin Anton Buzdin Anton Buzdin |
| author_sort |
Maksim Sorokin |
| title |
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_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_sort |
experimental and meta-analytic validation of rna sequencing signatures for predicting status of microsatellite instability |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/acc6c406b73b4c85a65a3ca797d6170a |
| work_keys_str_mv |
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