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Research Project
Non-invasive, innovative and promising strategy for early diagnosis of breast cancer through the establishment of urinary volatile metabolomic profiles of breast cancer patients as well as from breast cancer tissues and breast cancer cell lines
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Publications
Volatomic pattern of breast cancer and cancer-free tissues as a powerful strategy to identify potential biomarkers
Publication . Silva, Catarina; Perestrelo, Rosa; Silva, Pedro; Capelinha, Filipa; Tomás, Helena; Câmara, José S.
Breast cancer (BC), ranked as the fifth amongst all cancers, remains at the top of women’s cancers
worldwide followed by colorectal, lung, cervix, and stomach cancers. The main handicap of most of the
screening/diagnostic methods is based on their low sensitivity and specificity and the invasive behavior
of most sampling procedures. The aim of this study was to establish the volatomic pattern of BC and
cancer-free (CF) tissues (n = 30) from the same patients, as a powerful tool to identify a set of volatile
organic metabolite (VOM) potential BC biomarkers which might be used together or complement with
the traditional BC diagnostics strategies, through the integration of chromatographic data, obtained by
solid-phase microextraction followed by gas chromatography-mass spectrometry (SPME/GC-qMS),
with chemometric tools. A total of four metabolites: limonene, decanoic acid, acetic acid and furfural
presented the highest contribution towards discrimination of BC and CF tissues (VIP > 1, p < 0.05). The
discrimination efficiency and accuracy of BC tissue metabolites was ascertained by ROC curve analysis
that allowed the identification of some metabolites with high sensitivity and specificity. The results
obtained with this approach suggest the possibility of identifying endogenous metabolites as a platform
to find potential BC biomarkers and pave the way to investigate the related metabolomic pathways in
order to improve BC diagnostic tools. Moreover, deeper investigations could unravel novel mechanistic
insights into the disease pathophysiology.
Untargeted urinary 1H NMR-based metabolomic pattern as a potential platform in breast cancer detection
Publication . Silva, Catarina L.; Olival, Ana; Perestrelo, Rosa; Silva, Pedro; Tomás, Helena; Câmara, José S.
: Breast cancer (BC) remains the second leading cause of death among women worldwide.
An emerging approach based on the identification of endogenous metabolites (EMs) and the
establishment of the metabolomic fingerprint of biological fluids constitutes a new frontier in medical
diagnostics and a promising strategy to differentiate cancer patients from healthy individuals. In this
work we aimed to establish the urinary metabolomic patterns from 40 BC patients and 38 healthy
controls (CTL) using proton nuclear magnetic resonance spectroscopy (1H-NMR) as a powerful
approach to identify a set of BC-specific metabolites which might be employed in the diagnosis of
BC. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied to a 1H-NMR
processed data matrix. Metabolomic patterns distinguished BC from CTL urine samples, suggesting
a unique metabolite profile for each investigated group. A total of 10 metabolites exhibited the
highest contribution towards discriminating BC patients from healthy controls (variable importance
in projection (VIP) >1, p < 0.05). The discrimination efficiency and accuracy of the urinary EMs were
ascertained by receiver operating characteristic curve (ROC) analysis that allowed the identification
of some metabolites with the highest sensitivities and specificities to discriminate BC patients from
healthy controls (e.g. creatine, glycine, trimethylamine N-oxide, and serine). The metabolomic
pathway analysis indicated several metabolism pathway disruptions, including amino acid and
carbohydrate metabolisms, in BC patients, namely, glycine and butanoate metabolisms. The obtained
results support the high throughput potential of NMR-based urinary metabolomics patterns in
discriminating BC patients from CTL. Further investigations could unravel novel mechanistic
insights into disease pathophysiology, monitor disease recurrence, and predict patient response
towards therapy.
An integrative approach based on GC–qMS and NMR metabolomics data as a comprehensive strategy to search potential breast cancer biomarkers
Publication . Silva, Catarina Luís; Perestrelo, Rosa; Capelinha, Filipa; Tomás, Helena; Câmara, José S.
Introduction Globally, breast cancer (BC) is leading at the top of women's diseases and, as a multifactorial disease, there
is the need for the development of new approaches to aid clinicians on monitoring BC treatments. In this sense, metabo lomic studies have become an essential tool allowing the establishment of interdependency among metabolites in biological
samples.
Objective The combination of nuclear magnetic resonance (NMR) and gas chromatography–quadrupole mass spectrometry
(GC–qMS) based metabolomic analyses of urine and breast tissue samples from BC patients and cancer-free individuals
was used.
Methods Multivariate statistical tools were used in order to obtain a panel of metabolites that could discriminate malignant
from healthy status assisting in the diagnostic feld. Urine samples (n=30), cancer tissues (n=30) were collected from BC
patients, cancer-free tissues were resected outside the tumor margin from the same donors (n=30) while cancer-free urine
samples (n=40) where obtained from healthy subjects and analysed by NMR and GC–qMS methodologies.
Results The orthogonal partial least square discriminant analysis model showed a clear separation between BC patients and
cancer-free subjects for both classes of samples. Specifcally, for urine samples, the goodness of ft (R2
Y) and predictive
ability (Q2
) was 0.946 and 0.910, respectively, whereas for tissue was 0.888 and 0.813, revealing a good predictable accuracy.
The discrimination efciency and accuracy of tissue and urine metabolites was ascertained by receiver operating charac teristic curve analysis that allowed the identifcation of metabolites with high sensitivity and specifcity. The metabolomic
pathway analysis identifed several dysregulated pathways in BC, including those related with lactate, valine, aspartate and
glutamine metabolism. Additionally, correlations between urine and tissue metabolites were investigated and fve metabo lites (e.g. acetone, 3-hexanone, 4-heptanone, 2-methyl-5-(methylthio)-furan and acetate) were found to be signifcant using
a dual platform approach.
Conclusion Overall, this study suggests that an improved metabolic profle combining NMR and GC–qMS may be useful
to achieve more insights regarding the mechanisms underlying cancer.
Madeira wine volatile profile. A platform to establish madeira wine aroma descriptors
Publication . Perestrelo, Rosa; Luís, Catarina; Câmara, José S.
In the present study we aimed to investigate the volatile organic compounds (VOCs) that
may potentially be responsible for specific descriptors of Madeira wine providing details about
Madeira wine aroma notes at molecular level. Moreover, the wine aroma profile, based on the
obtained data, will be a starting point to evaluate the impact of grape variety (Malvasia, Bual, Sercial,
Verdelho and Tinta Negra), type (sweet, medium sweet, dry and medium dry), and age (from 3 to
20 years old) on Madeira wine sensorial properties. Firstly, a comprehensive and in-depth Madeira
wine volatile profiling was carried out using headspace solid-phase microextraction combined
with gas chromatography-mass spectrometry (HS–SPME/GC–qMS). Secondly, a relation among the
varietal, fermentative and aging aroma compounds, and their aroma descriptors with the Madeira
wine sensorial properties was assessed. A total of 82 VOCs, belonging to different chemical families
were identified, namely 21 esters, 13 higher alcohols, ten terpenic compounds, nine fatty acids,
seven furanic compounds, seven norisoprenoids, six lactones, four acetals, four volatile phenols and
one sulphur compound. From a sensorial point of view, during the aging process the wine lost its
freshness and fruitiness odor related to the presence of some varietal and fermentative compounds,
whereas other descriptors such as caramel, dried fruits, spicy, toasty and woody, arose during ageing.
The Maillard reaction and diffusion from the oak were the most important pathways related with
these descriptors. A relationship-based approach was used to explore the impact of grape variety,
wine type, and age on Madeira wine sensorial properties based on shared number of VOCs and
their odors.
Untargeted fingerprinting of cider volatiles from different geographical regions by HS-SPME/GC-MS
Publication . Perestrelo, Rosa; Silva, Catarina L.; Silva, Pedro; Medina, Sonia; Pereira, Regina; Câmara, José S.
The volatomic fingerprint of ciders produced in different geographical regions from Madeira Island was estab lished using headspace solid phase microextraction combined with gas chromatography mass spectrometry (HS SPME/GC–MS) in order to explore the effects of geographical region on the volatile pattern ciders in addition to
identify potential molecular geographic markers. A total of 107 volatile organic compounds (VOCs) belonging to
different chemical families were identified from which 50 VOCs are common to all ciders analysed. Significant
differences in the relative content of VOCs from ciders of different geographical regions were observed. The
potential of the identified VOCs for ciders discrimination according to region was assessed through chemometric
tools, such as principal components analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The
PCA showed significant differences among ciders from different island geographical regions. Fifteen VOCs re sponsible for ciders discrimination were identified by PLS-DA. Fifteen VOCs, namely five terpenoids, four al cohols, three acids and three esters, present variable importance in projection (VIP) values higher than one. Our
findings provide relevant information related to volatile signature of ciders produced in Madeira Island, which
may be a useful tool to cider-making process contributing to improve the quality of the final product. In addition,
the geographical discrimination recognizes the unique and distinctive characteristics that will allow in the future
to protect the quality and typicity of products originating in certain geographical regions.
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Funding agency
Fundação para a Ciência e a Tecnologia
Funding programme
OE
Funding Award Number
SFRH/BD/97039/2013