Hypoxic signalling in pancreatic NETs (pNETs)

#4378

Introduction: In a genomic profiling study conducted as part of the COMPOSE Phase III multicentre open-labelled clinical trial we assessed 9 pNET patients, 2 of which showed upregulation of CA9 and hypoxic signalling. Hypoxic tumour cells present CA9 for extracellular proton channelling, maintenance of intracellular pH and to acidify and thereby vascularise and immune-suppress the TME. In normoxia, EGLN1-3 hydroxylate proline residues of HIF1A for its subsequent ubiquitination by the VHL-complex resulting in degradation and repression of its target genes.

Aim(s): In a case study we compared hypoxic and normal tumour profiles, mapped co-expression with CA9 and assessed upstream regulator levels and tumour gene profiles to understand mechanisms of hypoxic signalling in pNETs.

Materials and methods: FFPE tumour samples from diagnosis were differentially assessed for mRNA expression and annotated SNVs for functional assessment.

Conference:

Presenting Author: Walter T

Authors: Walter T, Smutna V, Srirajaskanthan R, Capdevila J, Qin Y,

Keywords: hypoxia, pNET, HIF1A, CA9, Case study, hypoxic, genomic profiling,