Identification of the anoikis-related prognostic gene signature in pancreatic adenocarcinoma

Abstract Pancreatic adenocarcinoma (PAAD) remains a tumor with high malignancy and poor prognosis. Anoikis can regulate tumor cell invasion and metastasis, which in turn leads to poor prognosis for cancer patients. However, the role of anoikis-related genes (ARGs) in PAAD remains unclear. In our study, we performed a comprehensive bioinformatics analysis to construct a prognostic gene model. Correlations between ARGs and tumor immune infiltration, tumor mutation burden and microsatellite instability were assessed using Spearman correlation analysis. A total of 23 ARGs were upregulated in PAAD. Functional enrichment analysis revealed that these 23 ARGs were mainly involved in proteoglycans in cancer, regulation of anoikis, lipid and atherosclerosis, focal adhesion, and regulation of apoptotic Prognostic analysis showed that patients with PAAD with high expression of PTK2, ITGB1, EGFR, CASP8, BCL2L1, and CASP3 had a low survival rate. The prognostic ARGs model constructed using the above six prognostic genes was constructed to predict the overall survival of PAAD patients. There was a significant correlation between prognostic ARGs and immune cell infiltration and tumor mutation burden, while there was no correlation with microsatellite instability. Meanwhile, knockdown of BCL2L1 expression could inhibit the proliferation of pancreatic cancer cells. In conclusion, we performed a comprehensive bioinformatics analysis to identify PAAD patients containing six genes (PTK2, ITGB1, EGFR, CASP8, BCL2L1, and CASP3). Further studies are needed to validate our findings.