Combining micro-RNA and protein sequencing to detect robust biomarkers for Graves’ disease and orbitopathy

Zhang, Lei; Masetti, Giulia; Colucci, Giuseppe; Salvi, Mario; Covelli, Danila; Eckstein, Anja; Kaiser, Ulrike; Draman, Mohd Shazli; Muller, Ilaria; Ludgate, Marian; Lucini, Luigi; Biscarini, Filippo

doi:10.1038/s41598-018-26700-1

Cited by 38 publications

(40 citation statements)

References 66 publications

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“…[24] Although the biological activity of TWEAK is complex, it is known to be activated in inflammatory autoimmune disease and may serve as a reliable diagnostic and prognostic biomarker. Identifying new biomarkers and therapeutic targets other than TSHR for GD and GO by combining microRNA and protein sequencing [25] can improve our understanding of the pathogenesis of these disorders and lead to the development of effective treatments.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-like weak inducer of apoptosis induces inflammation in Graves’ orbital fibroblasts

Lee

Kim

et al. 2018

PLoS ONE

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Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), along with its receptor fibroblast growth factor-inducible (Fn)14, is associated with various biological activities including inflammation. However, its role in the pathogenesis of Graves’ orbitopathy (GO) is unknown. In this study, we investigated the mechanism by which TWEAK regulates inflammatory signaling in orbital fibroblasts from GO patients. We found that TWEAK and tumor necrosis factor-α (TNFA) mRNA levels were upregulated in GO as compared to non-GO tissue samples. TWEAK, TNF receptor (TNFR)1, TNFR2, and TNFR superfamily member 12A mRNA, and TWEAK and Fn14 protein levels were increased by interleukin (IL)-1β and TNF-α treatment. Treatment with exogenous recombinant TWEAK increased the transcript and protein expression of the pro-inflammatory cytokines IL-6, IL-8, and monocyte chemoattractant protein-1 to a greater extent in GO than in non-GO cells, while treatment with the anti-Fn14 antibody ITEM4 suppressed TWEAK-induced pro-inflammatory cytokine release and hyaluronan production. Additionally, the serum level of TWEAK was higher in Graves’ disease patients with (341.86 ± 86.3 pg/ml) as compared to those without (294.09 ± 41.44 pg/ml) GO and healthy subjects (255.33 ± 39.38 pg/ml), and was positively correlated with clinical activity score (r = 0.629, P < 0.001) and thyroid binding immunoglobulin level (r = 0.659, P < 0.001). These results demonstrate that TWEAK/Fn14 signaling contributes to GO pathogenesis. Moreover, serum TWEAK level is a potential diagnostic biomarker for inflammatory GO, and modulating TWEAK activity may be an effective therapeutic strategy for suppressing inflammation and tissue remodeling in GO.

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Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-like weak inducer of apoptosis induces inflammation in Graves’ orbital fibroblasts

Lee

Kim

et al. 2018

PLoS ONE

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“…Also, it was reported that urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, is a DNA oxidative stress biomarker and a risk factor for cancer, atherosclerosis, and diabetes (Wu et al, 2004; Kawai et al, 2018). In diabetic patients with hyperglycemia, increased urinary 8-OHdG and leukocyte DNA has been reported, and the urinary 8-OHdG level in diabetes patients has been linked with the severity of diabetic nephropathy and retinopathy (Zhang G. et al, 2018; Zhang L. et al, 2018; Zhang X. G. et al, 2018). Various methods, including high-performance liquid chromatography (HPLC), with and without extraction, and enzyme-linked immunosorbent assays (ELISAs), are proposed to determine 8-OHdG in tissues and urine (Wu et al, 2004; Kawai et al, 2018).…”

Section: Types Of Biomarkersmentioning

confidence: 99%

“…Another study revealed that lysozyme is related to circulating RNA, extracellular vesicles, and chronic stress (Abey et al, 2017). Currently lysozyme as diagnostic biomarker has found applications in chronic stress (Abey et al, 2016), cancer metastasis (Brzozowski et al, 2018), cardiovascular markers, psychological research (Mishra, 2017), oral diseases (Lorenzo-Pouso et al, 2018), diabetes (Maciejczyk et al, 2017), wound healing (Abey et al, 2016), infectious diseases (Ghosh et al, 2018; Stjärne Aspelund et al, 2018), Graves' disease and orbitopathy (Zhang L. et al, 2018). Serum lysozyme has been used as a clinical biomarker for diagnosing sarcoidosis with high specificity (Ramos-Casals et al, 2019).…”

Section: Types Of Biomarkersmentioning

confidence: 99%

Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values

Dhama

Latheef

Dadar

et al. 2019

Front. Mol. Biosci.

221

172

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Various internal and external factors negatively affect the homeostatic equilibrium of organisms at the molecular to the whole-body level, inducing the so-called state of stress. Stress affects an organism's welfare status and induces energy-consuming mechanisms to combat the subsequent ill effects; thus, the individual may be immunocompromised, making them vulnerable to pathogens. The information presented here has been extensively reviewed, compiled, and analyzed from authenticated published resources available on Medline, PubMed, PubMed Central, Science Direct, and other scientific databases. Stress levels can be monitored by the quantitative and qualitative measurement of biomarkers. Potential markers of stress include thermal stress markers, such as heat shock proteins (HSPs), innate immune markers, such as Acute Phase Proteins (APPs), oxidative stress markers, and chemical secretions in the saliva and urine. In addition, stress biomarkers also play critical roles in the prognosis of stress-related diseases and disorders, and therapy guidance. Moreover, different components have been identified as potent mediators of cardiovascular, central nervous system, hepatic, and nephrological disorders, which can also be employed to evaluate these conditions precisely, but with stringent validation and specificity. Considerable scientific advances have been made in the detection, quantitation, and application of these biomarkers. The present review describes the current progress of identifying biomarkers, their prognostic, and therapeutic values.

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“…This is a relatively recent research field that could explain the different penetrance of genetic susceptibility, and could also represent the mechanism of interaction between genetic predisposition and environmental factors [127]. The analysis of miRNA, alone or associated with proteomics, has also an interesting potential as biomarker of TA, especially GD [128].…”

Section: Graves' Diseasementioning

confidence: 99%

The antigenic link between thyroid autoimmunity and breast cancer

Muller

Barrett-Lee

2020

Seminars in Cancer Biology

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The association between breast cancer and benign thyroid disorders, in particular thyroid autoimmunity, has been debated for decades. Autoantibodies to thyroid peroxidase, the hallmark of thyroid autoimmunity, have a higher prevalence among patients with breast cancer compared with the general population. Furthermore a correlation between their positivity and a better prognosis of breast cancer was found in several independent small-scale studies, even if such observation was not confirmed in a subsequent retrospective study conducted on the largest patient cohort to date. The thyroid and mammary glands present several biological similarities, therefore the hypothesis of an immune response to shared thyroid/breast antigens could in part explain the association between thyroid autoimmunity and breast cancer. The sodium iodide symporter is expressed in both glands, however it seems unlikely to be the key common antigen, considering that autoantibodies targeting it are rare. Instead thyroid peroxidase, one of the major thyroid autoantigens, is also expressed in breast tissue and therefore represents the main antigenic link between thyroid autoimmunity and breast cancer. Furthermore lactoperoxidase, an enzyme of the same family that shares structural similarities with thyroid peroxidase, is expressed in neoplastic breast cells and is responsible for the cross-reactivity with some autoantibodies to thyroid peroxidase. Novel strategies for the diagnosis and treatment of breast cancer might take advantage of the antigenic link between thyroid and breast tissues.

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Combining micro-RNA and protein sequencing to detect robust biomarkers for Graves’ disease and orbitopathy

Cited by 38 publications

References 66 publications

Tumor necrosis factor-like weak inducer of apoptosis induces inflammation in Graves’ orbital fibroblasts

Tumor necrosis factor-like weak inducer of apoptosis induces inflammation in Graves’ orbital fibroblasts

Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values

The antigenic link between thyroid autoimmunity and breast cancer

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