AMIGO2 as a Novel Biomarker Predicting Poor Prognosis and Associated with Adhesion-Driven Metastasis in Pancreatic Adenocarcinoma

TL;DR

AMIGO2 is overexpressed in pancreatic cancer and linked to poor outcomes, suggesting it could be a new biomarker and treatment target.

Contribution

AMIGO2 is identified as a novel driver of pancreatic cancer progression through adhesion and EMT pathways.

Findings

AMIGO2 overexpression is strongly associated with poor survival in pancreatic cancer patients.

Inhibiting AMIGO2 reduces cancer cell migration and invasion by restoring E-cadherin expression.

AMIGO2 is linked to focal adhesion and PI3K/AKT signaling pathways in pancreatic cancer.

Abstract

Pancreatic adenocarcinoma (PAAD), the predominant form of pancreatic cancer, is highly aggressive and refractory to current therapies. The Amphoterin-Induced Gene and ORF (AMIGO) family encodes three structurally related type I transmembrane proteins (AMIGO1-3) containing leucine-rich repeat and immunoglobulin-like domains, which mediate cell adhesion and signaling. Although AMIGO proteins have been implicated in neural development and tumor progression, their functional relevance in PAAD remains unclear. Here we identify AMIGO2 as a key driver of PAAD progression through integrated transcriptomic, proteomic, and functional analyses. Multi-cohort datasets (ONCOMINE, TCGA) and immunohistochemistry revealed marked AMIGO2 overexpression in PAAD tissues, with recurrent genetic alterations (~11%) and strong association with poor relapse-free and overall survival. Functional enrichment of AMIGO2-correlated genes indicated activation of focal adhesion and PI3K/AKT signaling. Consistently, inhibition of AMIGO2 expression in pancreatic cancer cells reduced migration and invasion while restoring E-cadherin expression, indicating inhibition of epithelial mesenchymal transition. Protein profiling from the Human Protein Atlas further confirmed elevated AMIGO2 expression in tumors. Together, these findings demonstrate that AMIGO2 promotes PAAD aggressiveness by enhancing adhesion- and EMT-associated pathways, establishing it as a potential prognostic biomarker and therapeutic target in pancreatic cancer.

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