Background:Papillary thyroid cancer (PTC) accounts for over 80-85% of all thyroid malignancies and presents a rising global incidence. Necroptosis plays a pivotal role in oncogenesis and immune regulation. However, the prognostic relevance of necroptosis-related genes (NRGs) in PTC remains inadequately explored. This study aims to construct a prognostic model for PTC based on NRGs and evaluate its predictive value for the prognosis of PTC patients. Methods:Using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), prognostic-related genes (PRGs) were screened via univariate Cox analysis and subsequently refined using least absolute shrinkage and selection operator (LASSO) regularization. Gene set enrichment analysis (GSEA) was then performed for each identified prognostic gene. GSEA was conducted for each PRG, and immune characteristics were analyzed for patients stratified by risk scores. Potential therapeutic agents for PTC were also predicted. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to evaluate messenger RNA (mRNA) and protein expression of PRGs in PTC samples. Results:Three PRGs (CXCL5, FNDC4, and TYRO3) were identified. Kaplan-Meier analysis demonstrated a significantly lower survival probability in the high-risk group compared to the low-risk group. Univariate and multivariate Cox analyses confirmed that the risk score was an independent prognostic factor, with a nomogram based on this score offering accurate prognosis prediction for patients with PTC. Notably, immune profiling revealed distinct differences between the high- and low-risk groups. Additionally, qRT-PCR results showed that the expression of CXCL5, FNDC4, and TYRO3 was higher in PTC tissues than in adjacent normal tissues. Conclusions:A necroptosis-related prognostic signature composed of CXCL5, FNDC4, and TYRO3 has been established for PTC. This signature is closely associated with the tumor microenvironment and holds promise for improving both the outcome prediction and long-term monitoring of PTC.
BACKGROUND:To investigate reasonable treatment modalities and prognostic factors for patients with differentiated thyroid carcinoma (DTC) bone metastases (BM).METHODS:The clinicopathological characteristics and follow-up data for all patients with DTC BM who received treatment in the Third Affiliated Hospital of Kunming Medical University between November 1, 1993 and December 31, 2016 were analyzed retrospectively with respect to mortality and survival rates. Multivariate analysis was performed using the Cox proportional hazard model.RESULTS:The 5- and 10-year overall survival (OS) rates were 51.5% and 17.2%, respectively, for all 60 patients. Univariate analysis showed that patients diagnosed with BM at <45 years of age, with controlled thyroid-stimulating hormone (TSH) levels and those undergoing surgery or 131I therapy had better prognoses. Patients with cervical vertebra metastases, multiple organ metastases other than bone, and those receiving chemotherapy had worse prognoses. Gender, pathological type, number of BM lesions, skeletal-related events (SREs) and whether or not the patient received radiotherapy were not related to prognosis. Cox regression analysis showed that age at diagnosis of BM, undergoing surgery for bone lesions, and not receiving chemotherapy were independent factors of favorable prognosis for patients with DTC BM.CONCLUSIONS:Patients with DTC BM have poor prognoses. Age at diagnosis with BM <45 years old, undergoing surgery for bone lesions, and not receiving chemotherapy were independent factors of favorable prognosis for patients with DTC BM. 131I combined with surgery for bone metastatic lesions may be the best treatment model for most patients with DTC BM disease.
Abstract Background Rapid progression contributes to treatment failure in anaplastic thyroid carcinoma (ATC) patients. In a preliminary study, we demonstrated that some hematopoietic factors may be involved in the progression of ATC. The adaptor protein LNK, which is a negative regulator of hematopoietic cytokine signalling, has been studied extensively in malignant hematopoietic cells. However, there are few studies on LNK in solid tumours. Methods Real-time PCR, immunohistochemistry (IHC) and western blot analysis of LNK were performed on ATC cells, differentiated thyroid cancer (DTC) cells and normal thyroid cells. In vitro assays (including pull-down, liquid chromatography-mass spectrometry (LC–MS), co-IP, MTT and colony formation) were performed to validate the effect of LNK on ATC progression and elucidate the molecular mechanisms. Results Compared with DTC cells and normal thyroid cells, ATC cells exhibit overexpression of LNK. In addition, LNK overexpression results in increased proliferation of ATC cells. Conversely, LNK knockdown significantly suppresses ATC cell proliferation. LC–MS identified the 14-3-3 ε/γ protein as a LNK binding partner. Finally, the results indicate that LNK overexpression significantly enhances the anti-apoptotic ability of ATC cells via the Akt-NFκB-Bcl-2/Bcl-xL pathway and that the oncogenic effect of LNK largely depends on 14-3-3 ε/γ binding. Conclusions The present study elucidated the important role of LNK in the growth of ATC opposite to its behaviour in the hematopoietic system and indicates that LNK is a potential target for the treatment of ATC.
Objective To explore the mechanism of hypoxia inducing interleukine (IL)-11 secretion in anaplastic thyroid carcinoma (ATC) cells and the mechanism of IL-11 promoting epithelial mesenchymal transition of ATC cells.Methods Knockdown of IL-11,hypoxia-inducible factor (HIF)-1α in ATC cells or treatment of ATC cells with Cobalt Chloride,recombinant human interleukin (rhIL)-11,IL-11 antibody,then the effects of these interventions on the invasion and migration ability of ATC cells and its mechanism were detected by enzyme-linked immunosorbent assay (ELISA),Transwell,Real-time polymerase chain reaction (PCR),Western blotting.Results Under treatment with Cobalt Chloride,the protein and mRNA expression of IL-11 increased in ATC cells.The number of invasive cells in the knockdown HIF-1α group (61.7 ±4.9,30.0 ±4.6) was less than that of the control group 261.7 ± 8.7 (P < 0.01),and the number of migrated cells (87.3 ± 4.5,73.8 ± 5.4) was less than the control group 337.3 ± 7.1 (P < 0.01).The expression ofphosphorylated Akt (p-Akt),phosphorylated glycogen synthase kinase 3β (p-GSK3β) and Snail protein was significantly increased after treatment with rhIL-11.The protein expression of p-Akt,p-GSK3β and Snail were significantly decreased after knockdown of IL-11 expression in ATC cells.Conclusion Hypoxia induced epithelial mesenchymal transition of ATC cells is the main mechanism of high invasion and migration of ATC cells.
Objective: To investigate prognostic factors for patients with medullary thyroid carcinoma (MTC). Methods:Clinical information and follow-up data of 123 patients with MTC treated in Yunnan Cancer Hospital and Sun Yat-sen Univer-sity Cancer Center between January 1,1995 and December 31, 2015 were retrospectively analyzed with respect to mortality and survival rates by using Kaplan-Meier survival analysis and Cox regression model. Results: The 5-year, 10-year and 15-year overall survival rates were 91. 6% , 77. 9% and 63. 4% % , respectively, for all patients. Univariate analysis showed that age, sex, preoperative serum calcitonin level, primary tumor size, local infiltration, cTNM stage, distant metastasis and surgery affected prognosis of patients. Cox regres-sion analysis showed that age, gender, primary tumor size, cTNM stage, distant metastasis and receiving surgery were inde-pendent prognostic factors for MTC patients. Conclusion: MTC patients aged <40 years had a better prognosis compared to those aged ≥40 years. Male, preoperative serum calcitonin level≥1000 pg/mL, primary tumor size >4 cm, local infiltra-tion, cTNM stage and distant metastasis were factors of unfavorable prognosis for patients with MTC. However, surgical treat-ment can significantly improve the prognosis of patients with MTC.
The supraclavicular artery island flap is a fasciocutaneous flap harvested from the supraclavicular and deltoid regions,it is a new technology for postoperative defect repair.This flap is considered to be an ideal choice for the reconstruction of head and neck defects because it is easily and rapidly harvested and provides hairless,thin-textured,good-color-match skin,with relatively low donor-site morbidity.In recent years,the anatomical research and clinical application of the supraclavicular island flap has been increasing.This paper reviewed the history,anatomy,harvest and application of supraclavicular artery flap in order to promote the application of the flap in the head and neck surgery.
Chemotherapy is widely used in the treatment of malignant tumors, but chemotherapy resistance seriously affects its effect. Meanwhile, chemotherapy resistance is one of the main reasons of treatment failure. Recently, researches show that lysosome, is the main site of eukaryotic cell protein degradation, plays an important role in tumor cell resistance to chemotherapy. This paper reviews the research progress of the relationship between lysosome and chemotherapy resistance. Key words: Lysosome; Neoplasms; chemotherapy resistance
Objective: To explore the effect of hematopoietic cytokines IL-11 on invasion and metastasis abilities of anaplastic thyroid cacinoma(ATC) cells. Methods: Real-time PCR was performed for examining the IL-11 mRNA expression in thyroid carcinoma cell lines, and IL-11 protein expression in the supernament of thyroid carcinoma cell lines was detected by ELISA. Molecular cloning was employed to construct IL-11 stable knockdown cell line; MTT assay was used to analyze the effect of IL-11 on the proliferation of ATC cells; Transwell and wound healing assays were employed to analyze the abilities of migration and invasion in ATC cells. Western blotting was used to detect the relative pathway proteins. SPSS statistical package 19.0 was used to analyze the date, and Student's t test was used for multiple comparisons. Results: The protein level of IL-11 were significantly lower in knock-down cell lines than that in negative control cell lines(21.55±1.69, 16.18±0.85, 26.37±2.00 vs 54.54±3.99, all P<0.05). Colony formation assays reveal that colony number between knock-down cells and negative control cells has no significance(P>0.05). Meanwhile, MTT assays show that there is no significance between knock-down cell lines and negative control cell line(P>0.05). However, Transwell invasion and migration assays show that number of migrated cells is increased when ATC cells were treated with rhIL-11(0-100 ng/ml)at increasing concentrations. Conclusion: IL-11 improves the migratory and invasive abilities of ATC cells via inducing EMT of ATC cells, and it can be used as a potential target for ATC molecular targeted therapy.