Project description:Background: Circulating miRNAs in pituitary adenoma would help patient care especially in non-functioning adenoma cases as minimally invasive biomarkers of tumor recurrence and progression. Aim: Our aim was to investigate plasma miRNA profile in patients with pituitary adenoma. Materials and Methods: 149 plasma and extracellular vesicle (preoperative, early- and late postoperative) samples were collected from 45 pituitary adenoma patients. Adenomas were characterized based on anterior pituitary hormones and transcription factors by immunostaining. MiRNA next generation sequencing was performed on 36 samples (discovery set). Individual TaqMan assay was used for validation on extended sample set. PA tissue miRNAs were evaluated by TaqMan array and literature data. Results: Global downregulation of miRNA expression was observed in plasma samples of pituitary adenoma patients compared to normal samples. Expression of 29 miRNAs and isomiR variants were able to distinguish preoperative plasma samples and normal controls. MiRNAs with altered expression in both plasma and different adenoma tissues were identified. 3, 7 and 66 miRNAs expressed differentially between preoperative and postoperative plasma samples in growth hormone secreting, FSH/LH+ and hormone-immunonegative groups, respectively. MiR-143-3p was downregulated in late- but not in early postoperative plasma samples compared to preoperative ones exclusively in FSH/LH+ adenomas. Plasma level of miR-143-3p discriminated these samples with 81.8% sensitivity and 72.3% specificity (AUC=0.79; p=0.02). Conclusions: Differentially expressed miRNAs in pituitary adenoma tissues have low abundance in plasma minimizing their role as biomarkers. Plasma miR-143-3p decreases in patients with FSH/LH+ adenoma indicated successful surgery, but its application for evaluating tumor recurrence needs further investigation.
Project description:Recurrent single-nucleotide and small indel somatic mutations were infrequent among the three adenoma subtypes. However, somatic copy-number alterations (SCNA) were identified in all three pituitary adenoma subtypes. Methylation analysis revealed adenoma subtype-specific DNA methylation profiles, with GHsecreting adenomas being dominated by hypomethylated sites. Likewise, gene-expression patterns revealed adenoma subtype-specific profiles. Integrating DNA methylation and gene-expression data revealed that hypomethylation of promoter regions are related with increased expression of GH1 and SSTR5 genes in GH-secreting adenomas and POMC gene in ACTH secreting adenomas. Finally, multispectral IHC staining of immune-related proteins showed abundant expression of PD-L1 among all three adenoma subtypes.
Project description:The chemotherapy monitoring is currently based on radiological (RECIST 1.1 guideline) and clinical evaluation every 3 months. Circulating markers as Carcino Embryonic Antigen (CEA), circulating tumour DNA and total cell free DNA represent an alternative approach to evaluate the response. In the field of metastatic colorectal cancer (mCRC) recent studies suggest that early evaluation could be clinically relevant. Indeed, early tumoral response seems to be correlated to overall survival. Moreover, post-operative morbidity increases with the number of prior chemotherapy treatments. Early evaluation could allow to modify chemotherapy regimens when response appears to be insufficient.
The aim of the present study is to evaluate, in a prospective cohort of patients treated with systemic IV chemotherapy (5 Fluorouracil +/- oxaliplatin +/- irinotecan) +/- targeted therapy as first line treatment for a mCRC, the correlation between early variations of circulating tumour markers including CEA, circulating tumour DNA and total cell free DNA, and the 3 months objective response as defined in the RECIST 1.1 guideline.
Project description:This series includes the four major subtypes of pituitary adenomas and normal post-mortem pituitary tissue; Data Transformation; Using Affymetrix Microarray Suite 5.0 global scaling was applied to the quantification data to adjust the average recorded to a target intensity of 100. Data were then exported into the bioinformatics software GeneSpring 6.0 (Silicon Genetics, Redwood City, CA) for further analysis. Data normalization was performed to scale the data so that the average intensity value on each array was 1 by dividing each expression value by the median of the expression levels on each chip. The individual gene expression levels for each of the 4 pituitary adenoma subtype arrays was divided by the expression level in the normal pituitary array. Thus, the data are presented as relative to the expression in normal pituitary tissue. Filtering was then performed to identify genes over-expressed or under-expressed at least 2.0 fold in tumours compared to normal pituitary. TABLE 1:; The genes / ESTs differentially overexpressed >= 2-fold in at least one pituitary adenoma subtype compared to normal pituitary. Negative values represent underexpression. Where genes are represented by more than one probe set, individual probe data sets are given. TABLE 2:; The genes / ESTs differentially underexpressed >= 2-fold in at least one pituitary adenoma subtype compared to normal pituitary. Negative values represent underexpression. Where genes are represented by more than one probe set, individual probe data sets are given.
Project description:This series includes the four major subtypes of pituitary adenomas and normal post-mortem pituitary tissue Data Transformation Using Affymetrix Microarray Suite 5.0 global scaling was applied to the quantification data to adjust the average recorded to a target intensity of 100. Data were then exported into the bioinformatics software GeneSpring 6.0 (Silicon Genetics, Redwood City, CA) for further analysis. Data normalization was performed to scale the data so that the average intensity value on each array was 1 by dividing each expression value by the median of the expression levels on each chip. The individual gene expression levels for each of the 4 pituitary adenoma subtype arrays was divided by the expression level in the normal pituitary array. Thus, the data are presented as relative to the expression in normal pituitary tissue. Filtering was then performed to identify genes over-expressed or under-expressed at least 2.0 fold in tumours compared to normal pituitary. TABLE 1: The genes / ESTs differentially overexpressed >= 2-fold in at least one pituitary adenoma subtype compared to normal pituitary. Negative values represent underexpression. Where genes are represented by more than one probe set, individual probe data sets are given. TABLE 2: The genes / ESTs differentially underexpressed >= 2-fold in at least one pituitary adenoma subtype compared to normal pituitary. Negative values represent underexpression. Where genes are represented by more than one probe set, individual probe data sets are given. Keywords = pituitary tumor Keywords: other
Project description:Histologic diagnosis of sellar masses can be challenging, particularly in rare neoplasms and tumors without definitive biomarkers. DNA methylation has recently emerged as a useful diagnostic tool. To illustrate the clinical utility of machine-learning-based DNA methylation classifiers, we report a rare case of primary sellar esthesioneuroblastoma diagnosed by DNA methylation classificiation but histologically mimicking a nonfunctioning pituitary adenoma.