AMIGO2 is a pivotal therapeutic target related to M2 polarization of macrophages in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a common kind of lethal cancer, with low early diagnostic rate and poor prognosis. In this study, we identified and verified the AMIGO2 with significant diagnostic and prognostic value in PDAC through LASSO regression combined with multiple machines learning methods, including RVM-RFE and Random Forest in TCGA and GEO datasets. The relevance between the expression of AMIGO2 and M2 polarization of macrophages was identified through pancancer, normal tissue, and cell lines data in TCGA, GTEx and CCLE datasets. The relevance between AMIGO2 and M2 polarization was then further identified in our local PDAC cohort. Finally, the role of AMIGO2 as cancer promoter and pivotal factor enrolled in M2 polarization was verified through siRNA transfection and M2 macrophages induction. These findings could facilitate diagnosis and treatment of PDAC. In addition, further research was deemed necessary on the deep mechanism between AMIGO2 and M2 polarization of macrophages in PDAC.

Role of AMIGO2 in cancer progression: Novel insights (Review)

“…The proliferation of PDAC cells was inhibited following AMIGO2 knockdown. Given previous research findings suggesting the involvement of AMIGO2 in the Akt pathway ( 14 ), Chen et al ( 34 ) hypothesized that AMIGO2 may activate M2 macrophage polarization via the Akt pathway, which requires further investigation to confirm.…”

“…Research has indicated limited efficacy of immunotherapeutic approaches for patients with pancreatic ductal adenocarcinoma (PDAC) ( 32 , 33 ). Chen et al ( 34 ) first observed high AMIGO2 expression in PDAC, and patients with increased AMIGO2 expression exhibited lower overall survival and disease-free survival than patients with low AMIGO2 expression. In addition, the authors found an association between AMIGO2 and M2 macrophage polarization.…”