N6-Methylandenosine-related lncRNAs as potential biomarkers for predicting prognosis and the immunotherapy response in pancreatic cancer.

Abstract

Emerging evidence has shown that the N⁶-methyladenosine (m⁶A) modification of RNA plays key roles in tumorigenesis and the progression of various cancers. However, the potential roles of the m⁶A modification of long noncoding RNAs (lncRNAs) in pancreatic cancer (PaCa) are still unknown. To analyze the prognostic value of m⁶A-related lncRNAs in PaCa, an m6A-related lncRNA signature was constructed as a risk model via Pearson's correlation and univariate Cox regression analyses in The Cancer Genome Atlas (TCGA) database. The tumor microenvironment (TME), tumor mutation burden, and drug sensitivity of PaCa were investigated by m⁶A-related lncRNA risk score analyses. We established an m⁶A-related risk prognostic model consisting of five lncRNAs, namely, LINC01091, AC096733.2, AC092171.5, AC015660.1, and AC005332.6, which not only revealed significant differences in immune cell infiltration associated with the TME between the high-risk and low-risk groups but also predicted the potential benefit of immunotherapy for patients with PaCa. Drugs such as WZ8040, selumetinib, and bortezomib were also identified as more effective for high-risk patients. Our results indicate that the m⁶A-related lncRNA risk model could be an independent prognostic indicator, which may provide valuable insights for identifying therapeutic approaches for PaCa.