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

Abstract 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.