Prognostic Gene Signature for lung adenocarcinoma with a Higher Risk for Treatment Failure and Accelerated cell cycle and cell proliferation Pathway Activity

Abstract

AbstractLung cancer is the most common of malignant cancers which represents poor prognosis and high invasive. However, the reliable prognosis genes signature and the differential between the genetic and epigenetic are remain unclear. Here, we confirmed 78 genes of signature A to construct a model to predicted the prognosis and the activity of tumorigenesis-related pathways. The score based on the 78 genes expression is high correlation with the cell cycle and cell proliferation activity. Based on the median of score, the lung adenocarcinoma patients were divided into two cohorts which presents different prognosis, tumorigenesis-related pathways activity. The high score group was enriched in the E2F target, mtorc1 signaling and MYC targets. The low score group can be identified as better prognosis subtype. Also, we used the GDSC data to predicted the PIM inhibitor (AZD1208) as the effective compounds for high score group patients, which is supported by a higher PIM1 and PIM2 expression in the score group. An integrative analysis of multi-omics data identified ECT2 as key nodes in a regulatory network related to the prognostic phenotype. In conclusion, our data identified a molecular classifier for the different score groups patients, and the high score group patients might benefit from treatment with PIM inhibitor.