Machine learning-enhanced insights into sphingolipid-based prognostication: revealing the immunological landscape and predictive proficiency for immunomotherapy and chemotherapy responses in pancreatic carcinoma

Abstract

Background: With a poor prognosis for affected individuals, pancreatic adenocarcinoma (PAAD) is known as a complicated and diverse illness. Immunocytes have become essential elements in the development of PAAD. Notably, sphingolipid metabolism has a dual function in the development of tumors and the invasion of the immune system. Despite these implications, research on the predictive ability of sphingolipid variables for PAAD prognosis is strikingly lacking, and it is yet unclear how they can affect PAAD immunotherapy and targeted pharmacotherapy. Methods: The investigation process included SPG detection while also being pertinent to the prognosis for PAAD. Both the analytical capability of CIBERSORT and the prognostic capability of the pRRophetic R package were used to evaluate the immunological environments of the various HCC subtypes. In addition, CCK-8 experiments on PAAD cell lines were carried out to confirm the accuracy of drug sensitivity estimates. The results of these trials, which also evaluated cell survival and migratory patterns, confirmed the usefulness of sphingolipid-associated genes (SPGs). Results: As a result of this thorough investigation, 32 SPGs were identified, each of which had a measurable influence on the dynamics of overall survival. This collection of genes served as the conceptual framework for the development of a prognostic model, which was carefully assembled from 10 chosen genes. It should be noted that this grouping of patients into cohorts with high and low risk was a sign of different immune profiles and therapy responses. The increased abundance of SPGs was identified as a possible sign of inadequate responses to immune-based treatment approaches. The careful CCK-8 testing carried out on PAAD cell lines was of the highest importance for providing clear confirmation of drug sensitivity estimates. Conclusion: The significance of Sphingolipid metabolism in the complex web of PAAD development is brought home by this study. The novel risk model, built on the complexity of sphingolipid-associated genes, advances our understanding of PAAD and offers doctors a powerful tool for developing personalised treatment plans that are specifically suited to the unique characteristics of each patient.

Keywords: immunotherapy response; machine learning; pancreatic carcinoma; prediction; sphingolipid.