Introduction: With the gradual increase in the incidence of thyroid cancer, people's attention to thyroid cancer has also gradually increased. Although the prognosis of thyroid cancer is rather mild compared to other cancers, it will still bring a heavy psychological burden on people who have been diagnosed. At present, the diagnosis of thyroid cancer mainly depends on ultrasound and percutaneous fine needle aspiration (pFNA). Due to the unsatisfactory accuracy of the diagnosis methods we use now, there are still some thyroid nodules that cannot be clearly diagnosed before surgery. Methods: In this article, we have searched for relevant research on blood markers of thyroid cancer in the past five years and categoried them into four groups. Discussion: Though we have not found a biomarker which can diagnose thyroid cancer both sensitively and specifically, we do found many substances that are related to it, and have the potential to recognize it and help the diagnosis. And perhaps combined models can do it better.

Thyroid cancer is the most prevalent endocrine malignancy with an increasing incidence in the past few decades. Neferine possesses various pharmacological activities, which have been applied in diverse disease models, including various tumors. However, the detailed effect and mechanism of neferine on thyroid cancer are still unclear. In the current study, the viability of IHH-4 and CAL-62 cells was examined by the CCK-8 assay. The effect of neferine on the proliferation, apoptosis, invasion, vascular endothelial growth factor (VEGF), epithelial-mesenchymal transition (EMT), and ferroptosis was evaluated by CCK-8, flow cytometry, western blot, and spectrophotometry assays. Mechanically, the expressions levels of Nrf2/HO-1/NQO1 signaling were first determined by a western blot, which was then verified by Nrf2 overexpression. In vivo validation was also conducted on BALB/c nude mice with an inoculation dose of 2 × 106 IHH-4 cells. The results showed that neferine repressed the viability of both IHH-4 and CAL-62 cells both in a dose-dependent way and in a time-dependent fashion, in which the IC50 value of neferine on IHH-4 and CAL-62 cells was 9.47 and 8.72 μM, respectively. Besides, neferine enhanced apoptosis but suppressed invasion, angiogenesis, and EMT of IHH-4 and CAL-62 cells. Moreover, neferine induced the activation of ferroptosis in thyroid cancer cells. Notably, it was revealed that the Nrf2/HO-1/NQO1 pathway was strongly associated with the effect of neferine on the modulation of thyroid cancer. Furthermore, these outcomes were validated in xenografted mice. Therefore, neferine exerted an antitumor effect and ferroptosis-inducing effect on thyroid cancer via inhibiting the Nrf2/HO-1/NQO1 pathway.

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