Integration of Multi-Omics Data To Understand the Multifaceted Role of RAMP1 across Different Cancer Types.
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da Costa Cabral Gabrielle, Rodrigues Letícia Almeida, de Almeida Cabral Candiago Júlia, Procópio João Felipe Fernandes Ferreira, Silva Júlia Costa Cerqueira, de Lima Maria Eduarda Barbosa, Gisela Ellery Costa Lima Ana Stella, da Costa Júnior José Valmir Falcão, de Araújo David Abner Santos, da Silva João Paulo Emiliano, de Almeida Oliveira Sofia Amancio, de Oliveira Calaça Farias Rafael, de Almeida Leonardo Prudêncio Coutinho, de Melo Salomão Belfort Sparapan, Xavier José Emerson, de Araújo Sandra Taveiros, de França-Júnior Raimundo Rodrigues, Dos Santos Lemos Gurgel Maria Amélia, de Carvalho Fraga Carlos Alberto
Аннотация
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.