Impact of Age-Related Genetic Differences on the Therapeutic Outcome of Papillary Thyroid Cancer

Abstract

The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide. PTC is the most common type of differentiated thyroid cancer and usually shows good prognosis. However, some PTC is driven to advanced stage by epithelial-mesenchymal transition (EMT)-mediated drug resistance, which is particularly noticeable in pediatric patients. There are limited options for systemic treatment, necessitating development of new clinical approaches. Here, we aimed to clarify genetic differences due to age of patients with PTC, and thereby aid in developing novel therapeutics. Patients with biochemically and histologically confirmed PTC were included in this study. PTC cells were acquired from young and older patients showing drug resistance, and were compared via microarray analysis. Cellular proliferation and other properties were determined after treatments with lenvatinib and sorafenib. In vivo, tumor volume and other properties were examined using a mouse xenograft model. Lenvatinib-treated group showed obvious suppression of markers of anti-apoptosis, EMT, and the FGFR signaling pathway, compared with control and Sorafenib-treated group. In the xenograft models, lenvatinib treatment induced significant tumor shrinkage and blocked the proto-oncogene Bcl-2 (B cell lymphoma/leukemia gene-2) and FGFR signaling pathway, along with reduced levels of EMT markers, compared with control and Sorafenib-treated group. Our findings clarify the age-dependent characteristics of pediatric PTC, giving insights into the relationship between young age and poor prognosis. Furthermore, it provides a basis for developing novel therapeutics tailored to the age at diagnosis.

Machine learning for the prediction of bone metastasis in patients with newly diagnosed thyroid cancer

“…Therefore, models are necessary to predict patients with TC at high risk for bone metastases, and to provide early attention and screening. In previous studies, 26–29 age has been demonstrated to have an impact on the prognosis of TC patients, and it has been reported that the risk of DM was significantly reduced in younger TC patients compared with older patients 30 . And we found that age was also an important feature influencing BM in our study.…”

MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis

“…We showed that Lenvatinib promoted the apoptosis pathway in a concentrationdependent manner and that LR increased the anti-apoptotic effects of Lenvatinib in both SMMC-7721 and Huh7 cells, which implies that LR formation is probably associated with inhibition of the apoptosis pathway. Several other studies have shown that the apoptosis pathway may be activated after Lenvatinib stimulation [20][21][22]. Although some studies reported that Lenvatinib did not dose-dependently suppress tumor growth and apoptosis in cell lines [14], it should be noted that instant culturing with Lenvatinib may not be enough to affect the apoptosis pathway [20].…”

“…MT1JP has previously been reported to act as a tumor suppressor in breast and bladder cancer [23,24] and it has been reported that MT1JP may inhibit the proliferation, invasion and migration of tumor cells [25,26]. Zhu et al reported that MT1JP could inhibit the tumorigenesis and enhance the cisplatin sensitivity of breast cancer cells through competitively binding to miR-24-3p [22]. In this study, overexpression of MT1JP in breast cancer cells significantly inhibited their proliferation and enhanced their cisplatin sensitivity, which seems to be discordant with our results.…”

“…Therefore, in the present study, we further explored the interaction between MT1JP and miR-24-3p in the apoptosis pathway. Previously, miR-24-3p has been shown to play an important role in regulating cell growth and metastasis in various types of cancer [22,28,29]. MiR-24-3p has also been identified as a key miRNA associated with activation of the Fig.…”

Effects of Anti-Cancer Drug Sensitivity-Related Genetic Differences on Therapeutic Approaches in Refractory Papillary Thyroid Cancer

“…After transfer process, the primary antibodies against CHOP purchased from Cell Signaling Technology; Danvers, MA, USA, Bcl-2, cytochrome c , Snail1, Zeb1, and histone H2B purchased from Abcam; and PKC, MEK, p-ERK, ERK, and β-actin purchased from Santa Cruz Biotechnology, Santa Cruz, CA, USA were maintained overnight at 4 °C. As detailed in previous research [ 70 ].…”