Abstract 3542
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 <0.001, respectively), with lower PDCD6 expression in higher stage and poorly differentiated CRCs. PDCD6 expression was also associated with 5-year OS (p = 0.003), and higher PDCD6 expression revealed a trend towards longer OS. PDCD6 and Ki67 expression were negatively correlated (rs = - 0.192, p = 0.002). Low and high PDCD6 expressers showed differential gene expression in several other cancer pathways.
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.
Clinical trial identification
Editorial acknowledgement
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.
Resources from the same session
3489 - Overall Survival (OS) and Metastasis-Free Survival (MFS) in men with Biochemically Relapsed (BCR) Prostate Cancer after radical prostatectomy (RP) managed with deferred Androgen Deprivation Treatment (ADT): A combined Johns Hopkins and CPDR study
Presenter: Catherine Marshall
Session: Poster Display session 3
Resources:
Abstract
4606 - ARCHES – the role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups
Presenter: Arnulf Stenzl
Session: Poster Display session 3
Resources:
Abstract
2975 - Updated survival analyses of a multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (CHEIRON study).
Presenter: Orazio Caffo
Session: Poster Display session 3
Resources:
Abstract
2708 - Real-world analysis of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving vs not receiving chemotherapy in the treatment sequence
Presenter: Alicia Morgans
Session: Poster Display session 3
Resources:
Abstract
2134 - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial
Presenter: Janet Brown
Session: Poster Display session 3
Resources:
Abstract
3504 - Risk of falls and fractures in patients with castration resistant prostate cancer (CRPC) treated with new hormonal agents – a meta-analysis of randomized controlled trials.
Presenter: Rodrigo Coutinho Mariano
Session: Poster Display session 3
Resources:
Abstract
2342 - Pain progression at initiation of chemotherapy in metastatic Castration-Resistant Prostate Cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of FIRSTANA
Presenter: Nicolas Delanoy
Session: Poster Display session 3
Resources:
Abstract
5331 - Pain evaluation in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the PARABO observation study
Presenter: Holger Palmedo
Session: Poster Display session 3
Resources:
Abstract
2823 - Time to castration resistant prostate cancer (CRPC) and the risk of developing immune disorders
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
1500 - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE
Presenter: Harriet Mintz
Session: Poster Display session 3
Resources:
Abstract