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autophagy protein LC3-II and decreased levels of p62.
Conclusion
Treatment with the HDACi SAHA resulted in induction of
apoptosis and autophagy in both CRC cells and at a lesser
extent in a relevant normal tissue model. Firstly, our
results may contribute to explain adverse effects of SAHA
on normal intestinal epithelial cells, and secondly,
identify a therapeutic window where tumor
radiosensitization can be achieved by SAHA.
PO-0977 Plasma lipidomics for predictive biomarker
analysis in rectal cancer.
P. Bulens
1,2
, A. Debucquoy
2
, K. Bloch
2
, S. Fieuws
2
, J.
Swinnen
2
, K. Haustermans
1,2
1
University Hospital Leuven, Radiation Oncology, Leuven,
Belgium
2
KU Leuven - University of Leuven, Oncology, Leuven,
Belgium
Purpose or Objective
Selection of patients with locally advanced rectal cancer,
eligible for individualized treatment strategies, is
hampered by the lack of reliable predictors of response.
Plasma markers based on liquid biopsies would allow
minimally invasive patient stratification. Most liquid
biopsy approaches are based on the detection of free
circulating DNA or tumor cells. Since the development and
progression of cancer is associated with dramatic changes
in lipid metabolism, we propose a radically different
approach based on alterations in circulating lipids.
Material and Methods
From prospectively collected plasma samples of 85 rectal
cancer patients at 3 time points (before chemoradiation
(CRT), 2 weeks into CRT, end of CRT), lipids were
extracted using a modified Bligh-Dyer protocol.
Samples
were subjected to mass spectrometry-based lipid profiling
on a fully operational lipidomics platform. This approach
allowed us to assess the concentration of approximately
200 different lipid species including phosphatidylcholine
(PC),
phosphatidylethanolamines
(PE),
phosphatidylinositol (PI), phosphatidylserine (PS) and
ceramides (Cer). Based on the assessment of these
species, discriminative lipid profiles of patients achieving
a pathologic complete response (pCR) and patients lacking
such response will be delineated using biostatistical
approaches including PCA analysis followed by LDA and
correction for false discovery due to multiple testing.
Results
13 out of 85 patients achieved a pCR (15,3%). Preliminary
analyses showed slightly less lipogenic profiles for patients
with pCR. This effect was most pronounced for the PC lipid
species
(Fig. 1)
. Furthermore, preliminary results
identified changes in plasma lipid species during CRT. A
steeper increase in lipogenicity (PC, PE, Cer) was observed
during CRT (time point 1 to 3) for patients achieving pCR
in comparison to patients without pCR. Statistical analyses
on the complete patient group are ongoing in order to
validate our findings and to develop a discriminative
marker panel with the most promising lipid markers.
Conclusion
Plasma lipidomics is a novel field for biomarker
development. Preliminary analyses show the potential of
lipid profiling to discriminate rectal cancer patients with
heterogeneous responses, treated with standard CRT.
Further work will lead to the development of a predictive
lipid plasma marker panel. Such a predictive panel might
be used to stratify patients for an individualized
treatment, thereby improving the quality of li fe for these
patients.
PO-0978 Potential predictive biomarkers to
chemoradiotherapy response in rectal cancer: a
lipidomic study.
F. Perrotti
1
, P. Del Boccio
2
, D. Pieragostino
2
, L.
Caravatta
1
, M. Di Tommaso
1
, C. Rosa
1
, M. Di Perna
1
, P.
Sacchetta
2
, D. Genovesi
1
1
"SS Annunziata" Hospital, Radiotherapy, Chieti, Italy
2
"G. D'Annunzio" University, Medical Oral and
Biotechnological Sciences, Chieti, Italy
Purpose or Objective
To highlight the lipid signature able to predict the tumor
response to chemoradiotherapy (CRT), in patients with
advanced rectal cancer (LARC), by using a Lipidomics
approach.
Material and Methods
Between March 2013 and September 2014, 18 patients
with LARC were treated with preoperative CRT at the
Radiation Oncology Unit of SS Annunziata Hospital in
Chieti – Italy. Sera were prospectively collected during
routine chemistry tests before treatment (T0) and at day
14° (T14) and 28° (T28) of CRT. An open Liquid
Chromatography tandem Mass Spectrometry (LC-MS/MS)
analysis was performed to characterize lipid expression at
T0. Differential lipids were validated by an independent
targeted approach and studied during treatment.
Results
Sixty-five lipids significantly differentiated responder (RP)
vs no-responder (NRP) patients; five lipids were validated
as predictive of response to CRT: Sphingomyelin (SM,
d18:2/18:1), Lysophosphatidylcholine (LPC, 16:0/0:0),
Lysophosphatidylcholine
(LPC,
15:1(9z)/0:0),
Lysophosphatidylethanolamine (LPE, 22:5/0:0) and
Phosphatidylcholine (PC, 40:2). Receiver Operator
Characteristic curve (ROC curve), generated combining
the pattern of the 5 validated lipids, showed an AUC of
0.95.
Conclusion
The prediction of response to neoadjuvant CRT in LARC
allows to personalize treatments and to improve response
rate and survival outcomes. In this study we focused on
serum lipids to define a differential profile able to predict
response. Our results showed a pattern of 5 lipids that
differentiated RP and NRP before treatment. The ongoing
confirmation of these results could provide a new insight