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TEDDY Proteomics Discovery Phase Study

ABSTRACT: In this set, we analyzed human plasma samples from The Environmental Determinants of Diabetes in the Young (TEDDY) Study. In total, 2,252 samples from 184 individuals were concatenated into 364 pooled samples from individuals that developed type 1 diabetes or islet autoimmunity and their matched controls. Samples were analyzed from the same individuals pre and post-autoimmunity onset paired against controls. Each pooled sample was depleted with MARS abundant protein depletion column (Agilent), digested with trypsin and labeled with 8-plex iTRAQ reagent. Samples were then multiplexed and fractionated into 24 fractions by high-pH reverse-phase chromatography (DOI: 10.1038/s41596-018-0006-9). Each fraction was analyzed by liquid chromatography tandem mass spectrometry.

INSTRUMENT(S): Waters M Class NanoAcquity UPLC, Thermo Orbitrap Velos with ETD

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Thomas Metz

PROVIDER: MSV000091560 | MassIVE | Mon Mar 27 08:32:00 BST 2023

REPOSITORIES: MassIVE

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Project description:Context: Papillary thyroid cancer (PTC) is the most common thyroid cancer with dramatically increasing worldwide. Accurate diagnosis is crucial to avoid unnecessary overtreatment for low-risk patients, but the currently available markers are still insufficient. tRNA-derived fragments (tRFs) are emerging as a new class of small non-coding RNAs due to their potential roles as novel biomarkers and therapeutic targets in cancer. However, their involvement in papillary thyroid carcinoma (PTC) is still unclear. Objectives: This study was performed to identify differentially expressed tRFs in PTC and investigate the role of serum tRFs to discriminate PTC from nodular goiters (NGs).Methods and Materials: tRF expression profiles were measured in pooled sera from patients with PTCs (n=6), NGs (n=6) and healthy subjects (n=6) using high-throughput sequencing (cohort1). One selected tRF candidate was validated in the same individual samples (cohort1) by qRT-PCR. The confirmed tRF was further validated in a larger second cohort including patients with PTCs (n=30), NGs (n=20) and healthy individuals (n=18).Results: Our sequencing results showed that circulating tRFs were differentially expressed in patients with PTC compared with those with NG and healthy people. After the validation in individual samples, tRF-Pro-AGG-018 was confirmed as differentially elevated in serum samples of patients with PTC. These results were further confirmed in a larger second cohort. Moreover, tRF-Pro-AGG-018 exhibited good diagnostic performance with a sensitivity of 0.7222 and a specificity of 0.8846 for PTC and it was associated with several targeted genes of PTC. Conclusions: Our study identified that the serum tRFs were differentially expressed in PTC compared with NG and healthy individuals. Notably, circulating tRF-Pro-AGG-018 was found to have a significant elevation in patients with PTC and exhibited good diagnostic performance with relatively high sensitivity and specificity for PTC. Our findings suggest tRFs might serve as novel circulating biomarkers in predicting patients with PTC, which may prevent unnecessary thyroid surgeries for low-risk and benefit from optimal

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TEDDY Proteomics Discovery Phase Study

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