Identification and Verification of a New Anoikis-Related Signature and Subgroups in Pancreatic Ductal Adenocarcinoma

Abstract

Background: Anoikis, a process crucial for maintaining tissue homeostasis, is implicated in tumor initiation and progression, particularly in pancreatic ductal adenocarcinoma (PDAC), known for its dismal prognosis. Understanding the molecular mechanisms underlying anoikis is imperative for unraveling PDAC pathogenesis. This study aimed to investigate the role of anoikis-related genes (ARgs) in PDAC prognosis and their interaction with the tumor immune environment. Methods: Differential expression analysis of ARgs between tumor tissues and normal tissues was conducted utilizing The Cancer Genome Atlas (TCGA) dataset. Then, utilizing weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis, ARgs with prognostic relevance were discovered as differentially expressed hub genes. Subsequently, these hub ARgs were employed to construct risk signatures, and a consensus cluster analysis was conducted. Predictive values of risk groups and molecular subtypes, alongside characteristics of tumor immune microenvironment, were analyzed to accurately predict the prognosis. Combined with risk signatures and molecular subtypes, validation of prognostic classification models was achieved through external datasets and RT-PCR experiments. Results: We identified six hub ARgs, divided patients into two groups according to their expression as the basis of consensus cluster analysis, established an ARgs risk signature based on four of these ARgs, divided patients into high-risk and low-risk groups, and accurately predicted their prognosis. Furthermore, by combining the above classification, the two subgroups showed significant differences in their prognostic outcomes and immune microenvironment characteristics. To further validate our findings, we utilized data from the International Cancer Genome Consortium (ICGC). RT-PCR was performed to verify the expressions of hub ARgs. Conclusion: Our findings underscore the role of anoikis in shaping the tumor microenvironment and PDAC progression. Moreover, the established risk signature and classification exhibit close associations with the immune microenvironment, showing potential for prognostic predictions in PDAC patients.