The TIF-1γ autoantigen in patients with dermatomyositis and thyroid cancer: from case series to preliminary mechanistic exploration

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Abstract
Objectives: This study aimed to explore the relationship between dermatomyositis (DM) and thyroid cancer and the role of transcriptional intermediary factor 1γ (TIF-1γ) in the pathogenesis of cancer-associated DM. Methods: Five cases of DM with thyroid cancer, including one with metastasis, were summarized and analyzed. Published cases of DM with thyroid cancer were reviewed. Subsequently, a bidirectional two-sample Mendelian randomization (MR) analysis was performed to investigate the relationship between thyroid cancer and myositis using inverse-variance weighting (IVW), MR-Egger, and weighted-median (WM) analyses. Finally, immunohistochemistry (IHC) and immunofluorescence (IF) analysis were performed to detect TIF-1γ in tumor tissues of a DM patient and a thyroid cancer patient without DM. Results: This article reports the first case of a patient with DM and metastatic papillary thyroid carcinoma (PTC), in whom recurrence of the rash prompted the detection of metastasis, with the rash resolving after surgical resection of the metastatic foci. MR analysis showed a potential causal relationship between thyroid cancer and myositis (OR = 1.398; 95% CI = 1.045–1.869; p = 0.029). A higher expression level of TIF-1γ was observed in tumor tissues of DM patients compared with those of thyroid cancer patients without DM by immunofluorescence (IF) analysis ( p < 0.0001). Conclusions: DM symptoms might represent a paraneoplastic phenomenon in patients with thyroid cancer, with the underlying pathological mechanisms requiring further exploration and TIF-1γ overexpression potentially serving as a trigger.

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