Comprehensive analysis identifies AMIGO2 as a potential prognosis biomarker of pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a highly aggressive form of cancer characterized by a low survival rate. Adhesion molecule with Ig like domain family 2 (AMIGO2), a cell adhesion molecule, has been found to be expressed abnormally in various solid tumors, but its specific role in PAAD has not yet been investigated. This study aimed to investigate the potential prognostic value of AMIGO2 in pan-cancer, especially in PAAD. METHODS: RNA profiles and corresponding clinical data of PAAD patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were obtained. Kaplan-Meier survival analysis was conducted to assess the relationship between AMIGO2 expression and overall survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to evaluate the functional enrichment of AMIGO2 in PAAD. Subsequently, immune infiltration and single-cell RNA (scRNA) sequencing analyses were employed to investigate the composition of immune cells. The half maximal inhibitory concentration (IC50) value was utilized to estimate the drug sensitivity associated with AMIGO2. Finally, in vitro experiments were conducted to assess the biological function of AMIGO2 in PAAD. RESULTS: AMIGO2 exhibited abnormal expression patterns and demonstrated prognostic significance in various types of cancer. AMIGO2 was observed to be up-regulated in PAAD tissues. Its high expression was indicative of a poor prognosis. Additionally, elevated level of AMIGO2 was found to be associated with mutations in KRAS and TP53, as well as with dysregulation of key cellular processes such as "MAPK signaling" and "p53 signaling pathway". Furthermore, AMIGO2 expression exhibited correlations with the infiltration of macrophages and cancer-associated fibroblasts. PAAD patients with high AMIGO2 expression were more sensitive to BRD4 inhibitor BI-2536. The growth of PAAD cells was found to be inhibited upon knockdown of AMIGO2. CONCLUSIONS: AMIGO2 was identified as prognostic factor in PAAD, suggesting its potential as a biomarker and therapeutic target for PAAD patients.