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

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...

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Main Authors: Dequan Liu, Lei Liu, Xiangyu Che, Guangzhen Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1525345/full
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author Dequan Liu
Lei Liu
Xiangyu Che
Guangzhen Wu
author_facet Dequan Liu
Lei Liu
Xiangyu Che
Guangzhen Wu
author_sort Dequan Liu
collection DOAJ
description 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 stage- and 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.
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spelling doaj-art-20931102b68540c9a64f1a972c1d35532025-01-22T07:14:54ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011310.3389/fcell.2025.15253451525345Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancerDequan LiuLei LiuXiangyu CheGuangzhen WuOncogenes 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 stage- and 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.https://www.frontiersin.org/articles/10.3389/fcell.2025.1525345/fullparadoxical genesbioinformaticstumor metabolismdiscordant gene-protein abundancetumor immune microenvironmentsignaling pathway
spellingShingle Dequan Liu
Lei Liu
Xiangyu Che
Guangzhen Wu
Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer
Frontiers in Cell and Developmental Biology
paradoxical genes
bioinformatics
tumor metabolism
discordant gene-protein abundance
tumor immune microenvironment
signaling pathway
title Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer
title_full Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer
title_fullStr Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer
title_full_unstemmed Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer
title_short Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer
title_sort discovery of paradoxical genes reevaluating the prognostic impact of overexpressed genes in cancer
topic paradoxical genes
bioinformatics
tumor metabolism
discordant gene-protein abundance
tumor immune microenvironment
signaling pathway
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1525345/full
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AT xiangyuche discoveryofparadoxicalgenesreevaluatingtheprognosticimpactofoverexpressedgenesincancer
AT guangzhenwu discoveryofparadoxicalgenesreevaluatingtheprognosticimpactofoverexpressedgenesincancer