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<p>Receptor Activity-Modifying Protein 1 (RAMP1) is a Calcitonin Receptor-Like Receptor (CALCRL)-associated protein with significant relevance in oncogenesis and tumor progression. It acts as a context-dependent allosteric modulator of GPCRs. This integrative review synthesizes evidence from multiple omics layers—transcriptomics, proteomics, epigenomics, and pan-cancer datasets—to clarify the role of RAMP1, its signaling pathways, and its relationship with the tumor microenvironment. Multi-omics integration highlighted several key findings: transcriptomic and regulatory signatures frequently associate RAMP1 overexpression with epithelial–mesenchymal transition; RAMP1 is associated with the coordinated activation of GPCR-dependent pro-tumorigenic pathways; and the CGRP/RAMP1 axis is associated with CD8<sup>+</sup> T-cell exhaustion and potential resistance to immune checkpoint inhibitors. Pan-cancer analyses revealed marked expression heterogeneity. RAMP1 is strongly overexpressed in hepatocellular carcinoma (LIHC) and downregulated in kidney renal clear cell carcinoma (KIRC), reinforcing the importance of context-specific interpretation. It also emerges as an unfavorable prognostic biomarker in osteosarcoma, rectal adenocarcinoma, prostate cancer, and Ewing sarcoma, suggesting its potential value as a strategic therapeutic target. Future studies should prioritize spatial transcriptomics and the pharmacological modulation of the CGRP/RAMP1 axis to refine precision oncology strategies.</p>

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Integration of Multi-Omics Data To Understand the Multifaceted Role of RAMP1 across Different Cancer Types

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月21日

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  • Gabrielle da Costa Cabral,
  • Letícia Almeida Rodrigues,
  • Júlia de Almeida Cabral Candiago,
  • João Felipe Fernandes Ferreira Procópio,
  • Júlia Costa Cerqueira Silva,
  • Maria Eduarda Barbosa de Lima,
  • Ana Stella Gisela Ellery Costa Lima,
  • José Valmir Falcão da Costa Júnior,
  • David Abner Santos de Araújo,
  • João Paulo Emiliano da Silva,
  • Sofia Amancio de Almeida Oliveira,
  • Rafael de Oliveira Calaça Farias,
  • Leonardo Prudêncio Coutinho de Almeida,
  • Salomão Belfort Sparapan de Melo,
  • José Emerson Xavier,
  • Sandra Taveiros de Araújo,
  • Raimundo Rodrigues de França-Júnior,
  • Maria Amélia dos Santos Lemos Gurgel,
  • Carlos Alberto de Carvalho Fraga

摘要

Receptor Activity-Modifying Protein 1 (RAMP1) is a Calcitonin Receptor-Like Receptor (CALCRL)-associated protein with significant relevance in oncogenesis and tumor progression. It acts as a context-dependent allosteric modulator of GPCRs. This integrative review synthesizes evidence from multiple omics layers—transcriptomics, proteomics, epigenomics, and pan-cancer datasets—to clarify the role of RAMP1, its signaling pathways, and its relationship with the tumor microenvironment. Multi-omics integration highlighted several key findings: transcriptomic and regulatory signatures frequently associate RAMP1 overexpression with epithelial–mesenchymal transition; RAMP1 is associated with the coordinated activation of GPCR-dependent pro-tumorigenic pathways; and the CGRP/RAMP1 axis is associated with CD8+ T-cell exhaustion and potential resistance to immune checkpoint inhibitors. Pan-cancer analyses revealed marked expression heterogeneity. RAMP1 is strongly overexpressed in hepatocellular carcinoma (LIHC) and downregulated in kidney renal clear cell carcinoma (KIRC), reinforcing the importance of context-specific interpretation. It also emerges as an unfavorable prognostic biomarker in osteosarcoma, rectal adenocarcinoma, prostate cancer, and Ewing sarcoma, suggesting its potential value as a strategic therapeutic target. Future studies should prioritize spatial transcriptomics and the pharmacological modulation of the CGRP/RAMP1 axis to refine precision oncology strategies.