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The biological implications of PDCD6 dysregulation in colorectal cancer

Abstract Background Programmed cell death protein 6 (PDCD6) mediates apoptosis via p53 dependent and independent pathways and is implicated in many cancer hallmarks. A multi-omics analysis of colorectal cancer (CRC) cell lines identified PDCD6 as a candidate prognostic and predictive biomarker. PDCD6 is dysregulated in different cancers, but the role of PDCD6 in CRC is still poorly understood. Methods The clinicopathological data on 483 CRC patients treated at Mater Dei Hospital Malta between January 2008 and December 2011 were collated and tissue microarrays constructed in triplicate to represent central and peripheral tumour areas. PDCD6 protein expression was quantified by multiplex immunofluorescence (mIF; QuPath) along with fifteen other protein targets representing important cancer signalling and immune pathways. Expression of 770 genes was assessed using the NanoString nCounter® PanCancer Pathways Panel in a subset of 34 patients with low/high PDCD6 expression. Associations with clinicopathological parameters including disease-free survival and overall survival (OS) were calculated. Results Intra-tumoural PDCD6 protein expression was heterogeneous, having a higher expression at the tumour edge (p = 0.001). Invasive edge PDCD6 protein expression was significantly associated with TNM stage and tumour grade (p = 0.04 and Conclusions PDCD6 shows both inter- and intra-tumoural heterogeneity in CRC, with expression patterns consistent with a tumour suppressive function. Contrarily, wider literature suggests that PDCD6 might also have an intrinsic oncogenic role under certain circumstances, and further exploration of PDCD6 pleiotropism in CRC is warranted. Legal entity responsible for the study Romina Briffa. Funding REACH HIGH Scholars Programme Part-financed by the European Union, Operational Programme II; Cohesion Policy 2014-2020 "Investing in human capital to create more opportunities and promote the wellbeing of society.". Disclosure All authors have declared no conflicts of interest.