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REVIEW article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1525345

Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer

Provisionally accepted
Dequan Liu Dequan Liu Lei Liu Lei Liu Xiangyu Che Xiangyu Che Guangzhen Wu Guangzhen Wu *
  • Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China, Dalian, Liaoning Province, China

The final, formatted version of the article will be published soon.

    Oncogenes are typically overexpressed in tumor tissues and often linked to poor prognosis. However, recent advancements in bioinformatics have revealed that many highly expressed genes in tumors are associated with better patient outcomes. These genes, which act as tumor suppressors, are referred to as "paradoxical genes." Analyzing The Cancer Genome Atlas (TCGA) confirmed the widespread presence of paradoxical genes, and KEGG analysis revealed their role in regulating tumor metabolism. Mechanistically, discrepancies between gene and protein expression-affected by pre-and post-transcriptional modifications-may drive this phenomenon. Mechanisms like upstream open reading frames and alternative splicing contribute to these inconsistencies. Many paradoxical genes modulate the tumor immune microenvironment, exerting tumor-suppressive effects. Further analysis shows that the stageand tumor-specific expression of these genes, along with their environmental sensitivity, influence their dual roles in various signaling pathways. These findings highlight the importance of paradoxical genes in resisting tumor progression and maintaining cellular homeostasis, offering new avenues for targeted cancer therapy.

    Keywords: paradoxical genes, bioinformatics, tumor metabolism, discordant gene-protein abundance, Tumor immune microenvironment, signaling pathway

    Received: 09 Nov 2024; Accepted: 07 Jan 2025.

    Copyright: © 2025 Liu, Liu, Che and Wu. 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) or licensor 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.

    * Correspondence: Guangzhen Wu, Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China, Dalian, Liaoning Province, China

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