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.

Elucidating feed‑forward apoptosis signatures in breast cancer datasets: Higher FOS expression associated with a better outcome

“…As indicated by the above analyses, available data are consistent with the idea that feed-forward pathways can represent specific distinctions, based on what have been traditionally considered pro-proliferative TFs, between pro-proliferative and pro-apoptotic pathways. This conclusion was also recently reached for lower grade glioma and squamous cell lung cancer (23), where MYC and YY1, respectively, were identified as apoptosis-drivers. These distinctions may be useful in determining a more accurate overall survival rate among cancer patients, as well as possibly assist in development of therapies.…”

High levels of CCL2 or CCL4 in the tumor microenvironment predict unfavorable survival in lung adenocarcinoma

“…LUSC is an epidermoid carcinoma, and begins in the tissue that lines the air passages in the lungs. Most LUSCs are located centrally, usually in the larger bronchi that join the trachea to the lung . Advanced LUSC always undergoes central necrosis and cavitation because of a lack of blood supply …”

“…Most LUSCs are located centrally, usually in the larger bronchi that join the trachea to the lung. 2 Advanced LUSC always undergoes central necrosis and cavitation because of a lack of blood supply. 3 Lung adenocarcinoma is currently the most common type of NSCLC in lifelong non-smokers and women, but in recent years incidence has increased in smokers.…”