PracticeUpdate: Haematology & Oncology

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Identifying key molecular
alterations in prostate cancer
may help in diagnosis and
prognosis
Metabolic and proteomic alterations can
be identified in biopsy specimens from
patients with prostate cancer that enable
the distinction between benign and malignant
tissue, conclude results of a spectroscopy and
microarray study.
Margarita Fardilha, MD, of the University of
Aveiro, Portugal, explained that prostate cancer
remains a major health problem worldwide. Treat-
ment is still a challenge for urologists, as well as
the establishment of a clear prognosis.
Prognosis is compromised by the lack of sensi-
tivity and specificity of available markers. It is
imperative to unravel prostate cancer biology to
enable the identification of key molecular events
and molecules that aid in diagnosis, prognosis,
and the discovery of new therapeutic targets.
Dr Fardilha and colleagues set out to identify
metabolic and proteomic alterations that ena-
ble the distinction between prostate benign
and malignant tissue. Biopsies from prostate
tumours and adjacent benign tissue from the
central zone of the gland were obtained from
eight patients. Prostate-specific antigen blood
levels, prostate carcinoma stage (TNM), and
Gleason score were determined in all patients.
Each sample was divided and analysed using
two approaches: infrared spectroscopy, anti-
body microarray.
These approaches allowed for analysis of the
expression and phosphorylation state of 800
signalling proteins. The list of differentially
expressed/regulated proteins between normal
and tumour conditions was then subjected to
an extensive bioinformatics analysis to inte-
grate and complement all data with existing
studies.
Principal component analysis of spectroscopic
signals derived from prostate cancer biopsies and
adjacent benign tissues revealed different spectra
for each condition.
Dysregulations in lipid metabolism, lower
amounts of polysaccharides and glycogen, as
well as increased content of nucleic acids and
protein phosphorylation were the most relevant
alterations observed in prostate cancer tissues.
Moreover, 40 proteins were identified as differ-
entially expressed between the two conditions.
Thirteen proteins revealed alterations in their
phosphorylation levels.
Identification of known prostate cancer-related
proteins reinforced the fidelity of the screen.
Analysis of protein–protein interaction networks
and ontologies showed disruption of cell signalling
events during prostate carcinogenesis.
Dr Fardilha concluded that metabolomics and
proteomic approaches can provide vast informa-
tion about carcinogenic processes. Integration
of different “omic” approaches are increasingly
important when moving to the era of person-
alised medicine. This transition requires the
understanding of disease as an entire, integrated
pathophysiological process
Dr Fardilha and coinvestigators showed that
applying two distinct approaches to the same
set of samples enables retrieval of a substantial
amount of complementary information.
Using these approaches not only increases the
understanding of prostate carcinogenesis, but
also allows for identification of key molecular
alterations that may aid in accurate diagnosis/
prognosis and in the development of new, targeted
therapies.
PracticeUpdate Editorial Team at ECCO2017
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