Identification of specific feed-forward apoptosis mechanisms and associated higher survival rates for low grade glioma and lung squamous cell carcinoma

Abstract

The mechanisms of cell proliferation due to the overexpression of certain transcription factors (TFs) have been well documented in the cancer setting. However, many of these same TFs have pro-apoptotic effects, particularly when expressed or activated at high levels, a process referred to as feed-forward apoptosis (FFA). To determine whether cancers could be stratified on the basis of specific FFA signatures, RNASeq data representing samples from the cancer genome atlas were analyzed, revealing that high expression of the pro-proliferative TFs, MYC and YY1, is associated with a favorable outcome in low-grade glioma (LGG) and lung squamous cell carcinoma (LUSC), respectively. Analysis of the RNASeq data also led to the identification of specific apoptosis-effector genes whose expression levels correlate with increased survival rates, for both LGG and LUSC. Although FFA has been demonstrated as a general effect in cancer, in this report, for the first time, results identify specific TFs and their responsive effector genes that distinguish subsets of cancer samples undergoing more or less of a FFA process in a way that is associated with distinct patient survival rates.

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