Project description:A serum miRNA combination could be a favourable classifier to differentiate malignant pulmonary nodules from benign pulmonary nodules.
Project description:Thyroid nodules occur in about 60% of the population. Current diagnostic strategies, however, often fail at distinguishing malignant nodules before surgery, thus leading to unnecessary, invasive treatments. As proteins are involved in all physio/pathological processes, a proteome investigation of biopsied nodules may help correctly classify and identify malignant nodules and discover therapeutic targets. Quantitative mass spectrometry data-independent acquisition (DIA) enables highly reproducible and rapid throughput investigation of proteomes. An exhaustive spectral library of thyroid nodules is essential for DIA yet still unavailable. This study presents a comprehensive thyroid spectral library covering five types of thyroid tissue: multinodular goiter, follicular adenoma, follicular and papillary thyroid carcinoma, and normal thyroid tissue. Our library includes 925,330 transition groups, 157,548 peptide precursors, 121,960 peptides, 9941 protein groups, and 9826 proteins from proteotypic peptides. This library resource was evaluated using three papillary thyroid carcinoma samples and their corresponding adjacent normal thyroid tissue, leading to effective quantification of up to 7863 proteins from biopsy-level thyroid tissues.
Project description:The clinical diagnosis and treatment of small pulmonary nodules (suspected to be lung metastases) in advanced colorectal cancer patients remain controversy. Previous studies have shown that tumor-informed circulating tumor DNA (ctDNA) blood testing can sensitively detect residual cancer. Postoperative ctDNA in colorectal cancer patients is a valuable biomarker to identify minimal residual disease (MRD) after radical resection, which is possibly useful in redefining the risk group of patients and guiding postoperative treatment. This study aimed to explore the clinical value of therapeutic strategies based on tumor-informed ctDNA test in advanved colorectal cancer patients with small pulmonary nodules.
Project description:The presence of bilateral pulmonary nodules in lung cancer usually means distant metastases (M1a). We present an extraordinary example that challenges to look beyond this classification, and illustrates the potential benefits of a multidisciplinary re-evaluation in such a case.
Project description:Background: Fine needle aspiration biopsy (FNAB) is the gold-standard procedure for diagnosing malignant thyroid nodules. Indeterminate cytology is identified in 10-40% of cases and molecular testing may guide management in this setting. Current commercial options are expensive, and are either sensitive or specific. The aim of this study was to utilize next generation sequencing (NGS) technology to identify informative diversities in the microRNA (miRNA) expression profile of benign versus malignant thyroid nodules. Methods: Ex-vivo FNAB samples were obtained from thyroid specimens of patients that underwent thyroidectomy at a referral center. miRNA levels were determined using NGS and multiplexing technologies. Statistical analyses identified differences between normal and malignant samples and miRNA expression profiles that associate with malignancy were established. The accuracy of the miRNA signature in predicting histological malignancy was validated using a group of patient specimens with indeterminate cytology results. Results: 274 samples were obtained from 102 patients undergoing thyroidectomy. Of these samples, 71% were benign and 29% were malignant. Nineteen miRNAs were identified as statistically different between benign and malignant samples and were used to classify 35 additional nodules with indeterminate cytology (validation). The miRNA panel’s sensitivity, specificity, negative and positive predictive values and overall accuracy were 91%, 100%, 87%, 100% and 94%, respectively. Conclusion: Using NGS technology we identified a panel of 19 miRNAs that may be utilized to distinguish benign from malignant thyroid nodules with indeterminate cytology. Impact: Our panel may classify indeterminate thyroid nodules at higher accuracy than commercially available molecular tests.
Project description:We recently established that gene expression in PAXgene stabilized blood RNA distinguishes benign (BN) from malignant (MN) pulmonary nodules in high risk candidates with an AUC of 0.84. We now expand our studies to include incidental nodules identified in routine clinical settings using data from 603 patients analyzed on Illumina microarrays. We identify 300 gene probes achieving an AUC of 0.84 for Indeterminate Pulmonary Nodules (IPN) from 6-25 mm and 0.824 for IPN from 8-20 mm, outperforming 3 prominent clinical models that achieve AUCs of 0.60-0.689. We address the basis for these differences by in silico flow cytometry using CIBERSORT and identify significant differences between MN and BN patients including proportions of T-cells, M0 macrophages, NK cells, B cells and exhausted CD8 T-cells. We identify major increases in expression of genes promoting cell death and strong decreases in functions promoting transcription, lymphogenesis and cell viability. A preferential use of oxidative phosphorylation and a signature of mitochondrial dysfunction are also associated with the presence of a MN.
Project description:The presence of bilateral pulmonary nodules in lung cancer usually means distant metastases (M1a). We present an extraordinary example that challenges to look beyond this classification, and illustrates the potential benefits of a multidisciplinary re-evaluation in such a case. FFPE DNA from a patient with three primary tumors. Test samples were compared to normal tissue.