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Background <p>FMR1, a gene classically linked to Fragile X syndrome, functions as a multifunctional RNA-binding protein regulating RNA metabolism. Emerging evidence indicates its role in modulating cancer progression and tumor immunity, yet a comprehensive pan-cancer analysis to confirm its viability as a biomarker for cancer screening, prognosis, and precision therapy remains lacking.</p> Methods <p>We first validated FMR1 expression in renal cell carcinoma cell lines via qRT-PCR and assessed its functional role using colony-formation, wound-healing, and Transwell assays. Subsequently, we performed pan-cancer analyses by mining multi-omic data from public databases including UCSC Xena, TCGA, GTEx, TIMER, and TISIDB, integrating expression, prognosis, immune infiltration, and genetic alteration data.</p> Results <p>FMR1 was downregulated in renal cancer cell lines, and its overexpression inhibited cell proliferation and migration. Pan-cancer analysis revealed dysregulated FMR1 expression across multiple tumors. Low FMR1 expression correlated with poor prognosis in cancers like KIRC and SKCM. It also correlated with RNA methylation genes, immune/molecular subtypes, immune checkpoint genes, and immune cell infiltration. FMR1 amplification was the most frequent genetic alteration, and it demonstrated possibly improved predictive value compared to some traditional biomarkers.</p> Conclusion <p>FMR1 acts as a tumor suppressor in renal cancer and represents a promising pan-cancer biomarker for screening, prognostic evaluation, and immunotherapy response prediction, providing new insights for precision cancer therapy.</p>

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Identification of FMR1 as a novel cancer prognostic and immunotherapy biomarker through renal cancer experimental validation and pan-cancer analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月5日

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  • Huaqing Yan,
  • Fan Xu,
  • Xiaobo Cui,
  • Sinian Zheng,
  • Dianjun Yu,
  • Yiming Wu,
  • Bangbin Chen,
  • Rubing Li

摘要

Background

FMR1, a gene classically linked to Fragile X syndrome, functions as a multifunctional RNA-binding protein regulating RNA metabolism. Emerging evidence indicates its role in modulating cancer progression and tumor immunity, yet a comprehensive pan-cancer analysis to confirm its viability as a biomarker for cancer screening, prognosis, and precision therapy remains lacking.

Methods

We first validated FMR1 expression in renal cell carcinoma cell lines via qRT-PCR and assessed its functional role using colony-formation, wound-healing, and Transwell assays. Subsequently, we performed pan-cancer analyses by mining multi-omic data from public databases including UCSC Xena, TCGA, GTEx, TIMER, and TISIDB, integrating expression, prognosis, immune infiltration, and genetic alteration data.

Results

FMR1 was downregulated in renal cancer cell lines, and its overexpression inhibited cell proliferation and migration. Pan-cancer analysis revealed dysregulated FMR1 expression across multiple tumors. Low FMR1 expression correlated with poor prognosis in cancers like KIRC and SKCM. It also correlated with RNA methylation genes, immune/molecular subtypes, immune checkpoint genes, and immune cell infiltration. FMR1 amplification was the most frequent genetic alteration, and it demonstrated possibly improved predictive value compared to some traditional biomarkers.

Conclusion

FMR1 acts as a tumor suppressor in renal cancer and represents a promising pan-cancer biomarker for screening, prognostic evaluation, and immunotherapy response prediction, providing new insights for precision cancer therapy.