Faculty, Staff and Student Publications
Publication Date
8-2-2025
Journal
Scientific Reports
DOI
10.1038/s41598-025-12780-3
PMID
40753302
PMCID
PMC12318096
PubMedCentral® Posted Date
8-2-2025
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Humans, Biomarkers, Tumor, Immunohistochemistry, Neoplasms, Sequence Analysis, RNA, Tumor Microenvironment, Female, RNA-Seq, Gene Expression Regulation, Neoplastic, Biomarker assessment, Tumor microenvironment, Gene expression correlation, Cancer diagnostics, Immunohistochemistry, RNA sequencing, Cancer microenvironment, Tumour biomarkers, Gene expression analysis, Immunohistochemistry, RNA sequencing
Published Open-Access
yes
Recommended Citation
Kushnarev, Vladimir; Stupichev, Danil; Davitavyan, Suren; et al., "RNA Sequencing and Immunohistochemistry Jointly Improve Tumor Biomarker Interpretation" (2025). Faculty, Staff and Student Publications. 4826.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4826
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