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A targeted proteomics assay for the preoperative diagnosis of thyroid nodules

ABSTRACT: The multi-omics model shows high performance in diagnosing thyroid nodules. Especially for indeterminate nodules, while maintaining high specificity, the sensitivity has increased by 10% compared to BRAF V600E mutation.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Thyroid Nodule

DISEASE(S): Thyroid Cancer

SUBMITTER: Tiannan Guo

LAB HEAD: Tiannan Guo

PROVIDER: PXD046014 | Pride | 2026-01-21

REPOSITORIES: Pride

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			Action	DRS
	WAB20220330_TPM_Zhengyx_FNA_J_1238.wiff	Wiff
	WAB20220330_TPM_Zhengyx_FNA_J_1238.wiff.scan	Wiff
	WAB20220330_TPM_Zhengyx_FNA_J_1239.wiff	Wiff
	WAB20220330_TPM_Zhengyx_FNA_J_1239.wiff.scan	Wiff
	WAB20220330_TPM_Zhengyx_FNA_J_1242.wiff	Wiff

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Project description:Treatment with recombinant human growth hormone (rhGH) has been consistently reported to induce transcriptional changes in various human tissues including peripheral blood. For other hormones it has been shown that the induction of such transcriptional effects is conferred or at least accompanied by DNA-methylation changes. To analyse effects of short term rhGH treatment on the DNA-methylome we investigated a total of 24 patients at baseline and after 4-day rhGH stimulation. We performed array-based DNA-methylation profiling of paired peripheral blood mononuclear cell samples followed by targeted validation using bisulfite pyrosequencing. Unsupervised analysis of DNA-methylation in this short-term treated cohort revealed clustering according to individuals rather than treatment. Supervised analysis identified 239 CpGs as significantly differentially methylated between baseline and rhGH-stimulated samples (p<0.0001, unadjusted paired t-test), which nevertheless did not retain significance after adjustment for multiple testing. An individualised evaluation strategy led to the identification of 2350 CpG and 3 CpH sites showing methylation differences of at least 10% in more than 2 of the 24 analysed sample pairs. To investigate the long term effects of rhGH treatment on the DNA-methylome, we analysed peripheral blood cells from an independent cohort of 36 rhGH treated children born small for gestational age (SGA) as compared to 18 untreated controls. Median treatment interval was 33 months. In line with the groupwise comparison in the short-term treated cohort no differentially methylated targets reached the level of significance in the long-term treated cohort. We identified marked intra-individual responses of DNA-methylation to short-term rhGH treatment. These responses seem to be predominately associated with immunologic functions and show considerable inter-individual heterogeneity. The latter is likely the cause for the lack of a rhGH induced homogeneous DNA-methylation signature after short- and long-term treatment, which nevertheless is well in line with generally assumed safety of rhGH treatment. Bisulfite-converted DNA of PBMC from 24 patients before and after 4 days of rhGH treatment were hybridized to the Illumina Infinium HumanMethylation 450k BeadChip.

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A targeted proteomics assay for the preoperative diagnosis of thyroid nodules

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