Identification of signalling pathways involved in the oxidative stress response triggered by Low Temperature Plasma in prostate epithelial cells and the assessment of tumour-associated allelic expression in Prostate Cancer

Pairing of cancer genome and transcriptome data has revealed that heterozygous mutations
aren’t always expressed in cells. The potential for point mutation or genomic rearrangement to
alter tumour allelic expression has implications for understanding cellular heterogeneity and
application of treatments. Mutation of SPOP, PTEN and IDH-1 was assessed in 51 primary prostate
cancer cultures to establish allelic heterozygosity and ascertain whether oncogenic change to
coding regions altered allelic expression. No mutations were detected in the three genes,
although 18% of tested cultures had loss of heterozygosity in PTEN. The TMPRSS2-ERG fusion,
present in half of all prostate cancers, is selectively expressed at an allelic level by cancer stem
cells. Monoallelic expression didn’t correlate with TMPRSS2 promoter hypermethylation. Prostate
cultures expressed fusion transcript, however epigenetic features of monoallelically expressed
genes were not investigated in the epithelial subpopulations. Understanding of allelic chromatin
states may inform treatment strategies that permit tumour suppressor expression or oncogenic
protein repression.
Inability to predict indolent or aggressive progression of organ-confined prostate cancers has
created the problem of surgical overtreatment. Focal therapies targeting the tumour core are
being met with increasing rates of recurrence, necessitating development of novel treatments.
The anti-cancer properties of Low Temperature Plasma (LTP) are being explored in prostate
models where it produces autophagy and necrosis through generation of reactive species. Initial
gene expression response to LTP and the activation of upstream transcription factors were
analysed. LTP activated Nrf2, AP-1 and Notch signalling in patient matched prostate normal and
cancer cultures. The progenitor-containing cell fraction was more responsive to LTP than
differentiated epithelial cells in both transcription of response genes and nuclear accumulation of
active Notch1. When linked to cell-fate outcomes, these immediate molecular responses of
prostate cancer to LTP could be used as hallmarks of resistance or treatment efficacy in patients.