Project description:PURPOSE: Thyroid cancer is frequently difficult to diagnose due to an overlap of cytological features between malignant and benign nodules. This overlap leads to unnecessary removal of the thyroid in patients without cancer. While providing some improvement over cytopathologic diagnostics, molecular methods frequently fail to provide a correct diagnosis for thyroid nodules. These approaches are based on the difference between malignant nodules and normal adjacent thyroid tissue and assume that normal thyroid tissues are the same as benign nodules. However, in contrast to normal thyroid tissues, benign thyroid nodules can contain genetic alterations that can be found in cancerous nodules. PATIENTS AND METHODS: For the development of a new molecular diagnostic test for thyroid cancer, we evaluated DNA methylation in 109 thyroid tissues by using genome wide single base resolution DNA methylation analysis (Reduced Representation Bisulfite Sequencing). The test was validated in the retrospective cohort containing 64 thyroid nodules. RESULTS: By conducting Reduced Representation Bisulfite Sequencing in 109 thyroid specimens, we found significant differences between normal tissue, benign nodules, and cancer. Based on tissue-specific epigenetic signatures for benign and malignant nodules, we developed a new epigenetic approach for thyroid diagnostics. According to the validation cohort, our test has an estimated specificity of 97% (95% CI, 80 to 100), sensitivity of 100% (95% CI, 86 to 100), PPV of 97% (95% CI, 82-100), NPV of 100% (95%, 85 to 100). CONCLUSION: These data show that epigenetic testing can provide outstanding diagnostic accuracy for thyroid nodules by evaluating tissue specific DNA methylation.
Project description:Purpose: To clinically and proteomically profile a fine-needle aspirate biopsy (FNAB) from a single in situ cold thyroid nodule (CTN). Experimental Design: The FNAB lysate was digested with trypsin, and analysed by LC-MSMS on an LTQ Orbitrap Velos. Remaining peptides were separated by reversed-phase chromatography and fractions analysed as technical duplicates. Identified proteins were analysed by Gene Ontology and protein abundance were calculated using the Top3 label-free method. The proteomic data was complemented with ultrasonography and scintigraphy of the thyroid gland; and cytology of the CTN FNAB. Results: Sixty seven and 2,595 non-redundant protein groups (2 unique peptides) were identified from unfractionated and fractionated CTN FNAB, respectively. Label-free protein abundance ranged over 6 orders of magnitude from the most abundant proteins, haemoglobin and thyroglobulin; to the low-abundance protein SON. Many previously-reported markers of thyroid cancer were in the top 23% of the identified proteins. GO analysis revealed high-enrichment for extracellular vesicular exosome and vesicle (cellular component); regulation of biological quality (biological processes); and structural molecule activity (molecular function). Conclusions and Clinical Significance: The CTN was clinically-classified as benign. Proteomic data from FNAB can provide additional diagnostic candidates indicative of benign or cancerous CTN without the need for invasive surgical intervention.
Project description:In order to comprehensively investigate the genetic relationship between PTC tumors and benign nodules, we totally collected 127 fresh-frozen biopsies samples from 28 patients with concurrent thyroid benign nodule and PTC (n=20) or simple benign nodule (n=8). We carried out whole-exome sequencing on all the 127 biopsies samples and RNA-sequencing in total of 40 samples.
Project description:While thyroid nodules per se are frequent (4%–50%), thyroid cancer is rare (∼5% of all thyroid nodules). The minimally invasive Fine Needle Aspiration Cytology (FNAC) is the current gold standard for the diagnosis thyroid nodule malignancy. However, proper discrimination of follicular neoplasias often require more invasive diagnostic techniques. To develop a novel molecular classification system for thyroid cancer malignancy, we performed a genome-wide epigenetic profiling of 54 fresh frozen Follicular like thyroid samples using the Illumina Human DNA Methylation EPIC platform.
Project description:We profiled the microRNA expression of 5 pairs of PTC and normal thyroid tissues. All the tissues were immediately snap-frozen in liquid nitrogen and confirmed as papillary thyroid carcinoma by expert pathologists. Numerous deregulated mature microRNAs were identified comparing PTC tissues versus normal thyroid tissues. Details about the clinical-pathological characteristics of the samples are also provided.
Project description:In order to better understand the commonalities and differences in lateral root and nodule development, we compared their organogenesis and correlated this with changes in gene expression. To initiate lateral roots in Medicago truncatula we turned 2-day-old seedlings 135°, before returning them to their original axis of growth, while for nodule initiation we applied droplets of Sinorhizobium meliloti on the susceptibility zone of the root.
Project description:Next generation sequencing identifies a highly accurate microRNA panel that distinguishes well-differentiated thyroid cancer from benign thyroid nodules
Project description:Transcriptional analysis of 49 primary medullary thyroid carcinoma tumors. Comparisons MTCM918T vs MTC634 and MTCM918T vs MTCWT. 49 (52 hybridized tumors with 3 replicates) primary Medullary Thyroid Carcinoma (MTC) cases were hybridized onto a cDNA microarray in order to identify the unique markers for specific genetic classes of MTC.