The Significance of PAX8‐PPARγ Expression in Thyroid Cancer and the Application of a PAX8‐PPARγ‐Targeted Ultrasound Contrast Agent in the Early Diagnosis of Thyroid Cancer

Abstract

Objective. To investigate the significance of PAX8-PPARγ expression in thyroid cancer and the application of a PAX8-PPARγ-targeted ultrasound contrast agent in the early diagnosis of thyroid cancer. Methods. In this study, the expression of PAX8-PPARγ in thyroid cancer tissues, paracancer groups, and normal thyroid tissues was detected by western and immunohistochemical techniques; the effects of PAX8-PPARγ expression inhibition on thyroid cancer cell growth, clonogenic ability, and antiapoptosis were examined. The terminal carboxylactic acid/hydroxyacetic acid copolymer (PLGA-COOH) nanoparticles were prepared by the double emulsification solvent volatilization method. The in vitro cytotoxicity of the targeted contrast agent was detected by MTS and other methods; LD50 was used to evaluate its short-term in vivo toxicity after intraperitoneal injection in mice. Results. PAX8-PPARγ expression was significantly increased in thyroid cancer tissues, and the expression level of PAX8-PPARγ was closely correlated with TNM staging and lymph node metastasis ( P < 0.05). In addition, PAX8-PPARγ was also expressed at high levels in thyroid cancer cell lines relative to normal thyroid cells. MTS experiments showed that the PAX8-PPARγ-targeted ultrasound nanocontrast agent had no significant toxic side effects on thyroid cells; countess observed that the contrast agent had no effect on cell survival and mortality; the LD50 assay showed that the targeted contrast agent had a wide safety range. Western blot showed the expression of caspase-3, BAX, and Bcl-2 in thyroid cancer cells, indicating that the nanocontrast agent has a good biosafety. In vitro targeting experiments showed that there were more nanospheres aggregated around the cells in the targeted contrast group. In vivo targeting imaging of nude mice revealed that the ultrasound signal was significantly enhanced in the targeted group compared with the nontargeted group after 20 min of LIFU irradiation. Conclusion. PAX8-PPARγ overexpression in thyroid cancer cell lines and thyroid cancer tissues promoted the proliferation and antiapoptotic ability of thyroid cancer cells and promoted the tumorigenic ability in nude mice in vivo. We successfully prepared a PAX8-PPARγ-targeted ultrasound nanocontrast agent, which has regular morphology, uniform size, and high stability, and its liquid-gas phase change can be promoted at lower temperature. Therefore, this contrast agent can achieve US-targeted imaging and temperature phase transition function, and may have enhanced ultrasound imaging potential.

Molecular genetic markers of highly differentiated thyroid cancer (literature review and personal observations)

“…Genetic mutations of PAX8/PPARγ are more common in young patients with small tumours with vascular invasion [54,55]. A PAX8/PPARγ mutation is not a diagnostic sign of malignancy, but should prompt a thorough search for vascular or capsular invasion.…”

Nanomaterials: a promising multimodal theranostics platform for thyroid cancer

“…More nanospheres clustered around thyroid cancer cells bearing mice compared to the targeted mutation gene, and the ultrasonic signal of the targeted group was significantly enhanced compared to that of the non-targeted group. 40 Xie et al prepared BRAF V600E targeted lipid nanobubbles using thin-film hydration-sonication and avidin–biotin binding methods. BRAF V600E overexpression targeted nanobubbles had a better ultrasound enhancement effect and peak intensity of the time–intensity curve in differentiated thyroid cancer (DTC) cells, indicating that targeted lipid nanovesicles carrying BRAF V600E could be used as targeted ultrasound contrast agents for thyroid cancer.…”

Paired Box 5 (PAX5) Gene Has Diagnostic and Prognostic Potential in Nasopharyngeal Carcinoma

“…PAX2 can promote the proliferation and invasion of ovarian cancer by reprogramming fatty acid metabolism or inducing the formation of vascular-like structures. 5 , 6 PAX8 is expressed in thyroid, 7 kidney, 8 ovarian, 9 and breast 10 tumors. PAX5 is essential for the normal differentiation and maturation of B cells.…”