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Updated: May 28, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Microarray analysis of genes associated with cell surface NIS protein levels in breast cancer
Sasha J Beyer1, Xiaoli Zhang, Rafael E Jimenez
1Integrated Biomedical Sciences Graduate Program, The Ohio State University, Columbus, Ohio 43210, USA. sissy.jhiang@osumc.edu.
Background:
Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. We aimed to identify biomarkers associated with NIS expression such that mechanisms underlying NIS modulation in human breast tumors may be elucidated.
Methods:
Published oligonucleotide microarray data within the National Center for Biotechnology Information Gene Expression Omnibus database were analyzed to identify gene expression tightly correlated with NIS mRNA level among human breast tumors. NIS immunostaining was performed in a tissue microarray composed of 28 human breast tumors which had corresponding oligonucleotide microarray data available for each tumor such that gene expression associated with cell surface NIS protein level could be identified.
Results And Discussion:
NIS mRNA levels do not vary among breast tumors or when compared to normal breast tissues when detected by Affymetrix oligonucleotide microarray platforms. Cell surface NIS protein levels are much more variable than their corresponding NIS mRNA levels. Despite a limited number of breast tumors examined, our analysis identified cysteinyl-tRNA synthetase as a biomarker that is highly associated with cell surface NIS protein levels in the ER-positive breast cancer subtype.
Conclusions:
Further investigation on genes associated with cell surface NIS protein levels within each breast cancer molecular subtype may lead to novel targets for selectively increasing NIS expression/function in a subset of breast cancers patients.
Insights
Na+/I- symporter (NIS) expression in breast cancer is variable. Cysteinyl-tRNA synthetase is a potential biomarker for increasing NIS function in ER-positive breast cancers, aiding radionuclide therapy development.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Na+/I- symporter (NIS) mediates radioiodide uptake, crucial for thyroid cancer therapy.
- NIS expression in breast tumors suggests potential for targeted radionuclide therapy.
- Low NIS expression in many breast cancers limits therapeutic efficacy.
Purpose of the Study:
- To identify biomarkers associated with NIS expression in human breast tumors.
- To elucidate mechanisms regulating NIS modulation in breast cancer.
- To explore potential strategies for enhancing NIS function for breast cancer treatment.
Main Methods:
- Analysis of public microarray data to correlate gene expression with NIS mRNA levels in breast tumors.
- NIS immunostaining on a tissue microarray of 28 breast tumors with available microarray data.
- Correlation of gene expression with cell surface NIS protein levels.
Main Results:
- NIS mRNA levels showed minimal variation across breast tumors and normal tissues via microarray analysis.
- Cell surface NIS protein levels exhibited significant variability, exceeding that of NIS mRNA.
- Cysteinyl-tRNA synthetase was identified as a biomarker strongly associated with cell surface NIS protein in ER-positive breast cancer.
Conclusions:
- NIS mRNA levels do not reliably predict cell surface NIS protein levels in breast cancer.
- Cysteinyl-tRNA synthetase represents a promising biomarker for targeting NIS in ER-positive breast cancer.
- Further research into subtype-specific NIS-associated genes may reveal novel therapeutic targets.
