The prognostic significance of Twist in pancreatic cancer and its role in cancer promotion through the regulation of the immune microenvironment and EMT mechanisms

Abstract Objective The limited immunogenicity of pancreatic cancer (PAAD) contributes to its low responsiveness to immunotherapy, yet its underlying mechanism remains poorly understood. Twist, known for its involvement in tumor EMT and advancement, plays a significant role. The interplay between EMT and the tumor microenvironment (TME) emerges as a pivotal factor influencing tumor immunity and response to immunotherapy. Twist therefore has potential as a biomarker for gauging the outcome of tumour immunotherapy.This research aimed to assess the Twist's prognostic significance in PAAD and its relationship to immunotherapy response. Methods Transcriptional data and epigenetic alterations of Twist in pancreatic cancer, along with their impact on the prognosis of PAAD patients, were analyzed using databases. Functional enrichment analysis elucidated the biological role of Twist in PAAD. Subsequently, databases including CIBERSORT and TIDE were employed to investigate the association between Twist expression and immune cell infiltration, immune checkpoint genes, and immunotherapy sensitivity within the pancreatic cancer immune microenvironment. Results Twist mRNA expression was notably upregulated in PAAD, positively correlating with gene methylation levels. Analyses of Kaplan-Meier and Cox regression showed a correlation between better overall survival and lower Twist expression. Functional annotation indicated that Twist-associated differentially expressed genes (DEGs) were involved in EMT regulation and acute inflammation. Twist expression potentially impacts the therapeutic response to immune checkpoint inhibitors (ICIs). Furthermore, Twist was significantly overexpressed in pancreatic cancer cell lines and tissues, exhibiting a negative correlation with E-cadherin expression. Conclusion High Twist expression in PAAD signifies a grim prognosis. Its elevated levels not only contribute to tumor progression through EMT induction but also exert regulatory control over the immune microenvironment, leading to immunosuppression and diminished effectiveness of immunotherapy.