RNA sequencing and immunohistochemistry jointly improve tumor biomarker interpretation

RNA sequencing and immunohistochemistry jointly improve tumor biomarker interpretation

Abstract This study aimed to assess the correlation between RNA sequencing (RNA-seq) and immunohistochemistry (IHC) in detecting key cancer biomarkers across solid tumors, and then, to establish RNA-seq thresholds that accurately reflect clinical IHC classifications. Expression levels of nine biomar...

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Main Authors: Vladimir Kushnarev, Danil Stupichev, Suren Davitavyan, Kirill Kriukov, Basavaraja U. Shanthappa, Anna Butusova, Sofia Menshikova, Anna Belozerova, Anastasia Shvyrkova, Arina Tkachuk, Olga Khatenkova, Linda Balabanian, Ekaterina Postovalova, Jochen K. Lennerz, Funda Meric-Bernstam, Alexander Bagaev
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
Subjects:
Biomarker assessment
Tumor microenvironment
Gene expression correlation
Cancer diagnostics
Immunohistochemistry
RNA sequencing
Online Access:https://doi.org/10.1038/s41598-025-12780-3
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Summary:Abstract This study aimed to assess the correlation between RNA sequencing (RNA-seq) and immunohistochemistry (IHC) in detecting key cancer biomarkers across solid tumors, and then, to establish RNA-seq thresholds that accurately reflect clinical IHC classifications. Expression levels of nine biomarkers—ESR1, PGR, AR, MKI67, ERBB2, CD274, CDX2, KRT7, and KRT20—were analyzed in 365 formalin-fixed, paraffin-embedded samples from breast, lung, gastrointestinal, and other solid carcinomas. Correlations between RNA-seq data and IHC scores were determined using Spearman’s correlation coefficients, with RNA-seq cut-offs established to distinguish positive from negative IHC scores. The results revealed strong correlations for most biomarkers, with coefficients ranging from 0.53 to 0.89. RNA-seq thresholds were confirmed across internal and external cohorts, demonstrating high diagnostic accuracy (up to 98%) and precision in identifying biomarker expression levels. The analysis also highlighted the influence of tumor microenvironment and purity, particularly in the moderate correlation of 0.63 observed for PD-L1. Our study demonstrates that RNA-seq can serve as a robust complementary tool to IHC, offering objective and high-throughput biomarker assessment. The RNA-seq thresholds established provide a reliable method for determining biomarker positivity, supporting the integration of RNA-seq in clinical diagnostics to enhance precision, especially where tumor purity and microenvironment factors are significant.
ISSN:2045-2322

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