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ORIGINAL RESEARCH ARTICLE

Highly specific and sensitive gene panels for cancer screening: First application of only-normal and only-tumor genes

Gabriel Gil1 ,  Claudia Carricarte2 ,  Julio C. Drake-Pérez3 ,  Yasser Perera4,5 ,  Augusto Gonzalez1*
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1 Department of Theoretical Physics, Institute of Cybernetics, Mathematics and Physics, Havana, Cuba
2 Group of Computation, Faculty of Biology, University of Havana, Cuba
3 Department of General Physics, Faculty of Physics, University of Havana, Cuba
4 Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba
5 China-Cuba Biotechnology Joint Innovation Center, Yongzhou Zhong Gu Biotechnology Co., Ltd, Yongzhou, Hunan, China
Tumor Discovery, 025190035 https://doi.org/10.36922/TD025190035
Received: 7 May 2025 | Revised: 6 June 2025 | Accepted: 20 June 2025 | Published online: 17 July 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The traditional paradigm of gene expression dysregulation emphasizes log-fold differential expression, with differentially expressed genes presumed to play key roles in relevant biological processes. In cancer, where normal tissue and tumors occupy non-overlapping regions in gene expression space, we propose an alternative and broader framework based on differentially expressed only-tumor genes (T-genes) and non-differentially dysregulated only-normal genes (N-genes). N-genes exhibit expression intervals found exclusively in normal samples, while T-genes display intervals exclusive to tumor samples. These N- and T-genes serve as markers that can be combined into small gene panels capable of perfectly discriminating between normal and tumor tissues. In most cases, these panels highlight biologically significant properties, such as altered glutamine metabolism in tumors. We provide an inventory of perfect gene panels for 12 cancer types, with potential applications in diagnostics and immunotherapy. Significance: Highly specific and sensitive combinatorial gene panels for the identification of 12 types of solid tumors in humans were derived from RNA sequencing expression profiles reported by The Cancer Genome Atlas network (https://www.cancer.gov/ccg/research/genome-sequencing/tcga). The corresponding software is available at the GitHub repository https://github.com/gabriel-gil/GenePan. This study revisits the concept of cancer-related gene expression dysregulation by introducing N-genes and T-genes as novel dysregulation patterns that can be leveraged in diagnosis, tumor classification, and therapeutic interventions.

Keywords
Cancer
Combinatorial gene panel
Expression dysregulation
Only-normal genes
Only-tumor genes
Funding
The research was supported by the Financial and International Projects Office of the Ministry of Sciences, Cuba (project PN692LH007-095).
Conflict of interest
The authors declare that they have no competing interests.
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