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Evaluation of the EdgeSeq Precision Immuno-Oncology Panel for Gene Expression Profiling From Clinical Formalin-Fixed Paraffin-Embedded Tumor Specimens
Characterizing the tumor microenvironment (TME) of archived clinical tissues requires reliable gene expression profiling (GEP) of formalin-fixed paraffin-embedded (FFPE) samples. The EdgeSeq Precision Immuno-oncology Panel (PIP) is a targeted GEP assay designed for TME characterization but lacks wid...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197216/ https://www.ncbi.nlm.nih.gov/pubmed/35712667 http://dx.doi.org/10.3389/fcell.2022.899353 |
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author | Shi, Yang Ma, Xiaopeng Shen, Wei Liu, Tengfei Liang, Liang Liu, Silu Shen, Zhirong Zhang, Yun Zhang, Pei |
author_facet | Shi, Yang Ma, Xiaopeng Shen, Wei Liu, Tengfei Liang, Liang Liu, Silu Shen, Zhirong Zhang, Yun Zhang, Pei |
author_sort | Shi, Yang |
collection | PubMed |
description | Characterizing the tumor microenvironment (TME) of archived clinical tissues requires reliable gene expression profiling (GEP) of formalin-fixed paraffin-embedded (FFPE) samples. The EdgeSeq Precision Immuno-oncology Panel (PIP) is a targeted GEP assay designed for TME characterization but lacks widespread technical validation on a large cohort of clinical samples. Here, we evaluated its performance by exploring its concordance with multiple orthogonal platforms using 1,220 FFPE samples across various cancer types. Quantitative comparisons with RNA-seq and NanoString showed strong correlations at the sample level (median ρ = 0.73 and 0.81) and moderate correlations at the single-gene level (median ρ = 0.49 and 0.57). Gene signature analysis revealed high concordance with RNA-seq on widely used signatures for TME characterization and immune checkpoint inhibitor (ICI) efficacy prediction, though some genes in these signatures are not targeted by EdgeSeq PIP. From a histopathological viewpoint, the tumor/immune abundances derived from hematoxylin and eosin (H & E) staining were well recapitulated by the transcriptomic profiles assessed by EdgeSeq PIP. Furthermore, the mRNA level of PD-L1 assessed by EdgeSeq PIP was moderately correlated with the PD-L1 score (ρ = 0.65) estimated by immunohistochemistry (IHC); the mRNA level of CD8A aligned well (ρ = 0.55) with the IHC-derived abundance of CD8(+) T cells. Overall, our results showed that EdgeSeq PIP generated well-correlated data with independent approaches at mRNA, protein, and histological levels, thus providing strong technical support for further using EdgeSeq PIP in biomarker studies and companion diagnostic (CDx) development. |
format | Online Article Text |
id | pubmed-9197216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91972162022-06-15 Evaluation of the EdgeSeq Precision Immuno-Oncology Panel for Gene Expression Profiling From Clinical Formalin-Fixed Paraffin-Embedded Tumor Specimens Shi, Yang Ma, Xiaopeng Shen, Wei Liu, Tengfei Liang, Liang Liu, Silu Shen, Zhirong Zhang, Yun Zhang, Pei Front Cell Dev Biol Cell and Developmental Biology Characterizing the tumor microenvironment (TME) of archived clinical tissues requires reliable gene expression profiling (GEP) of formalin-fixed paraffin-embedded (FFPE) samples. The EdgeSeq Precision Immuno-oncology Panel (PIP) is a targeted GEP assay designed for TME characterization but lacks widespread technical validation on a large cohort of clinical samples. Here, we evaluated its performance by exploring its concordance with multiple orthogonal platforms using 1,220 FFPE samples across various cancer types. Quantitative comparisons with RNA-seq and NanoString showed strong correlations at the sample level (median ρ = 0.73 and 0.81) and moderate correlations at the single-gene level (median ρ = 0.49 and 0.57). Gene signature analysis revealed high concordance with RNA-seq on widely used signatures for TME characterization and immune checkpoint inhibitor (ICI) efficacy prediction, though some genes in these signatures are not targeted by EdgeSeq PIP. From a histopathological viewpoint, the tumor/immune abundances derived from hematoxylin and eosin (H & E) staining were well recapitulated by the transcriptomic profiles assessed by EdgeSeq PIP. Furthermore, the mRNA level of PD-L1 assessed by EdgeSeq PIP was moderately correlated with the PD-L1 score (ρ = 0.65) estimated by immunohistochemistry (IHC); the mRNA level of CD8A aligned well (ρ = 0.55) with the IHC-derived abundance of CD8(+) T cells. Overall, our results showed that EdgeSeq PIP generated well-correlated data with independent approaches at mRNA, protein, and histological levels, thus providing strong technical support for further using EdgeSeq PIP in biomarker studies and companion diagnostic (CDx) development. Frontiers Media S.A. 2022-05-27 /pmc/articles/PMC9197216/ /pubmed/35712667 http://dx.doi.org/10.3389/fcell.2022.899353 Text en Copyright © 2022 Shi, Ma, Shen, Liu, Liang, Liu, Shen, Zhang and Zhang. 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 | Cell and Developmental Biology Shi, Yang Ma, Xiaopeng Shen, Wei Liu, Tengfei Liang, Liang Liu, Silu Shen, Zhirong Zhang, Yun Zhang, Pei Evaluation of the EdgeSeq Precision Immuno-Oncology Panel for Gene Expression Profiling From Clinical Formalin-Fixed Paraffin-Embedded Tumor Specimens |
title | Evaluation of the EdgeSeq Precision Immuno-Oncology Panel for Gene Expression Profiling From Clinical Formalin-Fixed Paraffin-Embedded Tumor Specimens |
title_full | Evaluation of the EdgeSeq Precision Immuno-Oncology Panel for Gene Expression Profiling From Clinical Formalin-Fixed Paraffin-Embedded Tumor Specimens |
title_fullStr | Evaluation of the EdgeSeq Precision Immuno-Oncology Panel for Gene Expression Profiling From Clinical Formalin-Fixed Paraffin-Embedded Tumor Specimens |
title_full_unstemmed | Evaluation of the EdgeSeq Precision Immuno-Oncology Panel for Gene Expression Profiling From Clinical Formalin-Fixed Paraffin-Embedded Tumor Specimens |
title_short | Evaluation of the EdgeSeq Precision Immuno-Oncology Panel for Gene Expression Profiling From Clinical Formalin-Fixed Paraffin-Embedded Tumor Specimens |
title_sort | evaluation of the edgeseq precision immuno-oncology panel for gene expression profiling from clinical formalin-fixed paraffin-embedded tumor specimens |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197216/ https://www.ncbi.nlm.nih.gov/pubmed/35712667 http://dx.doi.org/10.3389/fcell.2022.899353 |
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