Publications of Vincent Bours
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See detailPredictive and prognostic role of peripheral blood eosinophil count in triple-negative and hormone receptor-negative/HER2-positive breast cancer patients undergoing neoadjuvant treatment
ONESTI, Concetta Elisa ULiege; JOSSE, Claire ULiege; Poncin, Aurélie ULiege et al

in Oncotarget (2018)

In current clinical practices, up to 27% of all breast cancer patients receive neoadjuvant chemotherapy. High pathological complete response rate is frequently associated with tumor-infiltrating ... [more ▼]

In current clinical practices, up to 27% of all breast cancer patients receive neoadjuvant chemotherapy. High pathological complete response rate is frequently associated with tumor-infiltrating lymphocytes. Additionally, circulating immune cells are also often linked to chemotherapy response. We performed a retrospective analysis on a cohort of 112 breast cancer patients (79 triple-negative, 33 hormone receptor-negative/HER2-positive) treated with standard neoadjuvant chemotherapy. Eosinophil and lymphocyte counts were collected from whole blood at baseline and during follow-ups and their associations with pathological complete response, relapse, disease-free and breast cancer-specific survival were analyzed. We observed a higher pathological complete response rate in patients who presented at baseline a relative eosinophil count ≥ 1.5% (55.6%) than in those with a relative eosinophil count < 1.5% (36.2%)(p = 0.04). An improvement in breast cancerspecific survival in patients with high relative eosinophil count (p = 0.05; HR = 0.336; 95% CI = 0.107–1.058) or with high relative lymphocyte count (threshold = 17.5%, p = 0.01; HR = 0.217; 95% CI = 0.060–0.783) were also observed. Upon combining the two parameters into the eosinophil x lymphocyte product with a threshold at 35.8, associations with pathological complete response (p = 0.002), relapse (p = 0.028), disease-free survival (p = 0.012) and breast cancer-specific survival (p = 0.001) were also recorded. In conclusion, the relative eosinophil count and eosinophil x lymphocyte product could be promising, affordable and accessible new biomarkers that are predictive for neoadjuvant chemotherapy response and prognostic for longer survival in triplenegative and hormone receptors-negative/HER2-positive breast cancers. Confirmation of these results in a larger patient population is needed. [less ▲]

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See detailBrain imaging and genetics in patients with congenital hypogonadotropic hypogonadism: a multicenter Belgian study.
VALDES SOCIN, Hernan Gonzalo ULiege; LIBIOULLE, Cécile ULiege; HARVENGT, Julie ULiege et al

in Jorgensen, Jens OL (Ed.) NENEG Abstract Book Communications (2018, April 19)

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See detailPheochromocytomas and pituitary adenomas in three patients with MAX exon deletions
Daly, Adrian ULiege; CASTERMANS, Emilie ULiege; Oudijk, Lindsey et al

in Endocrine-Related Cancer (2018)

Copy number variations (CNV), an important genetic mechanism in inherited tumor genetics, can affect large genetic regions or can be limited to smaller regions within genes, such deletions of single exons ... [more ▼]

Copy number variations (CNV), an important genetic mechanism in inherited tumor genetics, can affect large genetic regions or can be limited to smaller regions within genes, such deletions of single exons. Such exon deletions can be challenging to identify and sequencing can be normal in these cases. Multiplex ligation dependent probe amplification (MLPA) can identify CNV of individual exons. Mutations in the MAX gene are associated with a risk of sporadic and hereditary pheochromocytoma. As mutations in other pheochromocytoma related genes can also cause pituitary tumors (3P-Association), we studied whether MAX exon deletions were involved in the etiology of patients with an unexplained association of multiple endocrine neoplasia including pituitary adenoma and pheochromocytoma. Using MLPA we identified three patients with pheochromocytoma and pituitary adenomas who had normal MAX sequencing but presented germline heterozygous MAX exon deletions. The three patients had either acromegaly (n=2) or prolactinoma (n=1) in association with bilateral or recurrent pheochromocytoma. Two had germline heterozygous deletions of single exons of MAX, the other had a germline heterozygous deletion of MAX exons 1-3. MAX immunohistochemical staining was lost in the pheochromocytomas of all three patients and genetic analysis confirmed loss of heterozygosity in tumor DNA. A MAX exon deletion was also transmitted from one patient to a currently asymptomatic offspring. Screening studies of pheochromocytoma patients should take into account the potential for co-existing pituitary tumors. MLPA or other techniques to identify discrete MAX exon deletions should be considered in individuals with pheochromocytoma that are negative following comprehensive sequencing. [less ▲]

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See detailEhlers-Danlos syndrome in the University Hospital of Liege
KUKOR, Léna ULiege; BERTOLI, Sabrina ULiege; Bours, Vincent ULiege et al

Poster (2018, February 16)

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See detailNatural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers.
Latge, Guillaume ULiege; Poulet, Christophe ULiege; Bours, Vincent ULiege et al

in International Journal of Molecular Sciences (2018), 19(1),

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high ... [more ▼]

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers. [less ▲]

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See detailLe Syndrome de Kallmann: un vieux syndrome revisité par la génétique
VALDES SOCIN, Hernan Gonzalo ULiege; LIBIOULLE, Cécile ULiege; DEBRAY, François-Guillaume ULiege et al

in Urologic (2018), 14

Le contrôle neuroendocrinien de la reproduction chez l’homme est régi par un réseau d’environ 1.500 neurones hypothalamiques sécrétant la gonadotropin-releasing hormone (GnRH). Ce réseau module l’activité ... [more ▼]

Le contrôle neuroendocrinien de la reproduction chez l’homme est régi par un réseau d’environ 1.500 neurones hypothalamiques sécrétant la gonadotropin-releasing hormone (GnRH). Ce réseau module l’activité de l’axe de reproduction au cours de la vie. L’hypogonadisme hypogonadotrope congénital isolé (HHCI) est un syndrome clinique complexe, caractérisé par une insuffisance pubertaire partielle ou complète. Il peut découler d’une insuffisance hypothalamique sécrétoire de la GnRH ou d’une insuffisance de la sécrétion et/ou des effets des gonadotrophines hypophysaires. Chez l’homme, plusieurs gènes participant au développement olfactif et à la migration des neurones à GnRH interagissent pendant la vie embryonnaire. Les stéroïdes sexuels sont, à leur tour, nécessaires pour promouvoir la neurogenèse et le développement neurocognitif. Un nombre croissant de mutations de gènes participant à ce développement ont été identifiées comme étant responsables de HHCI. Sur base de la présence ou de l’absence d’un déficit de l’olfaction, l’HH est répertorié en deux syndromes, à savoir: HH avec altérations olfactives (syndrome de Kallmann) et l’hypogonadisme hypogonadotrophique idiopathique (IHH) avec une olfaction intacte ou normosmique (hypogonadisme IHH). Le syndrome de Kallmann (KS) est une condition hétérogène qui affecte 1 homme sur 5.000, avec un rapport homme/femme de 3/1. Le KS est associé à des mutations des gènes KAL1, FGFR1/FGF8, FGF17, IL17RD, PROK2/PROKR2, NELF, CHD7, HS6ST1, FLRT3, SPRY4, DUSP6, SEMA3A, SEMA7A, NELF, WDR11, SOX10, NSMF, AXL, FEZF1, DCC/NTN1 et KLB. Ces mutations entraînent des défauts de la migration neuronale, avec, comme possibles conséquences, un déficit variable au niveau de l’axe reproducteur, des troubles de l’olfaction, une surdité neurosensorielle. Des malformations y sont parfois associées, y compris un colobome, des syncinésies controlatérales, une malformation crâniofaciale et/ou une agénésie rénale. Dans cet article de synthèse, nous revisitons le syndrome de Kallmann vis-à-vis de ses conséquences sur la reproduction et sur le développement cérébral. [less ▲]

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See detailVariations of circulating cardiac biomarkers during and after anthracycline-containing chemotherapy in breast cancer patients
Freres, Pierre ULiege; Bouznad, N.; Servais, Laurence ULiege et al

in BMC Cancer (2018), 18(1),

Background: Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment ... [more ▼]

Background: Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment options. However, oncologists are concerned by the risk of long term treatment side effects, including congestive heart failure (CHF). Methods: In this study, we evaluated innovative circulating cardiac biomarkers during and after anthracycline-based neoadjuvant chemotherapy (NAC) in breast cancer patients. Levels of cardiac-specific troponins T (cTnT), N-terminal natriuretic peptides (NT-proBNP), soluble ST2 (sST2) and 10 circulating microRNAs (miRNAs) were measured. Results: Under chemotherapy, we observed an elevation of cTnT and NT-proBNP levels, but also the upregulation of sST2 and of 4 CHF-related miRNAs (miR-126-3p, miR-199a-3p, miR-423-5p, miR-34a-5p). The elevations of cTnT, NT-proBNP, sST2 and CHF-related miRNAs were poorly correlated, suggesting that these molecules could provide different information. Conclusions: Circulating miRNA and sST2 are potential biomarkers of the chemotherapy-related cardiac dysfunction (CRCD). Nevertheless, further studies and long-term follow-up are needed in order to evaluate if these new markers may help to predict CRCD and to identify the patients at risk to later develop CHF. © 2018 The Author(s). [less ▲]

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See detailInnovative methodology for the identification of soluble biomarkers in fresh tissues.
Costanza, Brunella ULiege; Turtoi, Anders; Bellahcene, Akeila ULiege et al

in Oncotarget (2018), 9(12), 10665-10680

The identification of diagnostic and prognostic biomarkers from early lesions, measurable in liquid biopsies remains a major challenge, particularly in oncology. Fresh human material of high quality is ... [more ▼]

The identification of diagnostic and prognostic biomarkers from early lesions, measurable in liquid biopsies remains a major challenge, particularly in oncology. Fresh human material of high quality is required for biomarker discovery but is often not available when it is totally required for clinical pathology investigation. Hence, all OMICs studies are done on residual and less clinically relevant biological samples. Here after, we present an innovative, simple, and non-destructive, procedure named EXPEL that uses rapid, pressure-assisted, interstitial fluid extrusion, preserving the specimen for full routine clinical pathology investigation. In the meantime, the technique allows a comprehensive OMICs analysis (proteins, metabolites, miRNAs and DNA). As proof of concept, we have applied EXPEL on freshly collected human colorectal cancer and liver metastases tissues. We demonstrate that the procedure efficiently allows the extraction, within a few minutes, of a wide variety of biomolecules holding diagnostic and prognostic potential while keeping both tissue morphology and antigenicity unaltered. Our method enables, for the first time, both clinicians and scientists to explore identical clinical material regardless of its origin and size, which has a major positive impact on translation to the clinic. [less ▲]

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See detailDrepakis : Contribution to the management of Sickle cell disease in the city of Kisangani (D.R. Congo)
Marini Djang'Eing'A, Roland ULiege; Batina Agasa, Salomon; Gulbis, Béatrice et al

Conference (2017, October 06)

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See detailTranscriptome wide analysis of natural antisense transcripts shows potential role in breast cancer
Wenric, Stéphane ULiege; El Guendi, Sonia; CABERG, Jean-Hubert ULiege et al

Poster (2017, May)

Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer ... [more ▼]

Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer. Among them, natural antisense transcripts (NAT) are RNA sequences which are complementary and overlapping to those of protein-coding transcripts (PCT). NATs were punctually described as regulating gene expression, and are expected to act more frequently in cis than other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired healthy tissues were analyzed by strand-specific RNA sequencing. To highlight the potential role of NATs in gene regulations occurring in breast cancer, three different gene extraction methods were used: differential expression analysis of NATs between tumor and healthy tissues, differential correlation analysis of paired NAT/PCT between tumor and healthy tissues, and NAT/PCT read count ratio variation between tumor and healthy tissues. Each of these methods yielded lists of NAT/PCT pairs that were demonstrated to be enriched in survival-associated genes on an independent cohort (TCGA). This work allows to highlight NAT lists that display a strong potential to affect the expression of genes involved in the breast cancer pathology. [less ▲]

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