scholarly journals Identification of Hub lncRNAs Along With lncRNA-miRNA-mRNA Network for Effective Diagnosis and Prognosis of Papillary Thyroid Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Haiyan Li ◽  
Feng Liu ◽  
Xiaoyang Wang ◽  
Menglong Li ◽  
Zhihui Li ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Prognostic Indicators ◽  
Validation Dataset ◽  
Papillary Thyroid ◽  
Cerna Network ◽  
Diagnosis And Prognosis ◽  
Potential Biomarkers

Long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and progression of different cancers and they have been potential biomarkers for cancer diagnosis and prognosis. As the most common endocrine malignancy, precise diagnosis and prognosis of papillary thyroid cancer (PTC) is of great clinical significance. Here, we aim to identify new hub lncRNAs for marking PTC and constructed prognostics signatures based on lncRNA- miRNA-mRNA competing endogenous RNAs (ceRNA) network to predict overall survival (OS) and disease-free survival (DFS) respectively. Five reliable hub lncRNAs were identified by integrating differential genes of four Gene Expression Omnibus (GEO) gene chips using the RobustRankAggreg (RRA) method. Based on differential analyses and interaction prediction, a lncRNA-mRNA co-expression network and a lncRNA-miRNA-mRNA ceRNA network were established. Then a comprehensive function characterization of the five hub lncRNAs was performed, including validation dataset testing, receiver operating characteristic (ROC) curve analysis, and functional analysis on two networks. All results suggest that these five hub lncRNAs could be potential biomarkers for marking PTC. The ceRNA network was used to identify RNAs which were associated with PTC prognosis. Two prognostic signatures were developed using univariate and step-wise multivariate Cox regression analyses and both of them were independent prognostic indicators for PTC OS and DFS. Tumor microenvironment difference analysis between high and low-risk patients showed that dendritic cells activated and macrophages M0 may be a possible target for immunotherapy of PTC. In addition, disclosing the potential drugs that may reverse the expression of hub genes may improve the prognosis of patients with PTC. Here, connectivity map (CMap) analysis indicates that three bioactive chemicals (pioglitazone, benserazide, and SB-203580) are promising therapeutic agents for PTC. So, the paper presents a comprehensive study on diagnosis, prognosis, and potential drug screening for PTC based on the five hub lncRNAs identified by us.

Overexpression of miR-127 Predicts Poor Prognosis and Contributes to the Progression of Papillary Thyroid Cancer by Targeting REPIN1

2020 ◽  
Author(s):  
Yinghe Sun ◽  
Wenhai Sun ◽  
Hui Hua ◽  
Jianhua Zhang ◽  
Qianqian Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Tnm Stage ◽  
Prognostic Indicators ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Cox Regression Analysis

AbstractPapillary thyroid cancer (PTC) is a major kind of thyroid cancer with increasing recurrence and metastasis. MiR-127 has been demonstrated to play roles in many cancers with dysregulation. However, the function of miR-127 is still unknown. This study aimed to explore a novel biomarker for the progression and prognosis of PTC. A set of 118 patients with PTC were collected from the Affiliated Hospital of Qingdao University. qRT-PCR was used to detect the expression of miR-127 in PTC tissues and cells. The association between miR-127 expression and the clinicopathological features of patients were evaluated by the χ2 test, and the prognostic value of miR-127 was evaluated by Kaplan–Meier analysis and Cox regression analysis. The effect of miR-127 on cell proliferation, migration, and invasion of PTC was analyzed by CCK-8 and transwell assay. miR-127 was found to be upregulated in PTC tissues and cells correlated with the TNM stage and poor prognosis of PTC patients. MiR-127 and the TNM stage were considered as two independent prognostic indicators for PTC. Moreover, overexpression of miR-127 significantly enhanced cell proliferation, migration, and invasion of PTC by targeting REPIN1. miR-127 may be involved in the progression of PTC, which provides a new therapeutic strategy for PTC.

TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer

2021 ◽  
Author(s):  
Yang Zhao ◽  
Cangang Zhang ◽  
Yanan Zhu ◽  
Xi Ding ◽  
Yikun Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Molecular Mechanisms ◽  
Methylation Status ◽  
Disease Free Survival ◽  
Papillary Thyroid ◽  
Advanced Tumor ◽  
Tumor Stages ◽  
Immunosuppressive Microenvironment

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among triggering receptor expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

scholarly journals Annual Hazard Rate of Recurrence in Middle Eastern Papillary Thyroid Cancer over a Long-Term Follow-Up

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3624
Author(s):  
Abdul K. Siraj ◽  
Sandeep Kumar Parvathareddy ◽  
Zeeshan Qadri ◽  
Khawar Siddiqui ◽  
Saif S. Al-Sobhi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Hazard Rate ◽  
Tumor Recurrence ◽  
Cox Regression ◽  
Middle Eastern ◽  
Treatment Strategies ◽  
Recurrence Risk ◽  
Papillary Thyroid ◽  
Cox Regression Analysis

Predicting the pattern of recurrence in papillary thyroid cancer (PTC) is necessary to establish optimal surveillance and treatment strategies. We analyzed changes in hazard rate (HR) for tumor recurrence over time in 1201 unselected Middle Eastern PTC patients. The changes in risk were further analyzed according to clinical variables predictive of early (≤5 years) and late (>5 years) recurrence using Cox regression analysis to identify patient populations that remain at risk. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 and 2 years (3.7%), with a second smaller peak between 13 and 14 years (3.2%). Patients receiving radioactive iodine (RAI) therapy had lower recurrence hazard compared to those who did not (1.5% vs. 2.7%, p = 0.0001). Importantly, this difference was significant even in intermediate-risk PTC patients (0.7% vs. 2.3%; p = 0.0001). Interestingly, patients aged ≥55 years and having lymph node metastasis were at persistent risk for late recurrence. In conclusion, we confirmed the validity of the double-peaked time-varying pattern for recurrence risk in Middle Eastern PTC patients and our findings could help in formulating individualized treatment and surveillance plans.

BRAFV600E Mutation is Associated with Decreased Disease-Free Survival in Papillary Thyroid Cancer

2016 ◽  
Vol 40 (7) ◽  
pp. 1618-1624 ◽  
Author(s):  
S. Fraser ◽  
C. Go ◽  
A. Aniss ◽  
S. Sidhu ◽  
L. Delbridge ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Disease Free Survival ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Free Survival ◽  
Disease Free

scholarly journals Comprehensive Analysis of Prognostic Alternative Splicing Signature Reveals Recurrence Predictor for Papillary Thyroid Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Mian Liu ◽  
Rooh Afza Khushbu ◽  
Pei Chen ◽  
Hui-Yu Hu ◽  
Neng Tang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Alternative Splicing ◽  
Papillary Thyroid Cancer ◽  
Molecular Mechanisms ◽  
Prediction Models ◽  
Cox Regression ◽  
Prognostic Biomarkers ◽  
Papillary Thyroid ◽  
Network Diagram ◽  
Prognostic Prediction

BackgroundAlternative splicing (AS) plays a key role in the diversity of proteins and is closely associated with tumorigenicity. The aim of this study was to systemically analyze RNA alternative splicing (AS) and identify its prognostic value for papillary thyroid cancer (PTC).MethodsAS percent-splice-in (PSI) data of 430 patients with PTC were downloaded from the TCGA SpliceSeq database. We successfully identified recurrence-free survival (RFS)-associated AS events through univariate Cox regression, LASSO regression and multivariate regression and then constructed different types of prognostic prediction models. Gene function enrichment analysis revealed the relevant signaling pathways involved in RFS-related AS events. Simultaneously, a regulatory network diagram of AS and splicing factors (SFs) was established.ResultsWe identified 1397 RFS-related AS events which could be used as the potential prognostic biomarkers for PTC. Based on these RFS-related AS events, we constructed a ten-AS event prognostic prediction signature that could distinguish high-and low-risk patients and was highly capable of predicting PTC patient prognosis. ROC curve analysis revealed the excellent predictive ability of the ten-AS events model, with an area under the curve (AUC) value of 0.889; the highest prediction intensity for one-year RFS was 0.923, indicating that the model could be used as a prognostic biomarker for PTC. In addition, the nomogram constructed by the risk score of the ten-AS model also showed high predictive efficiency for the prognosis of PTC patients. Finally, the constructed SF-AS network diagram revealed the regulatory role of SFs in PTC.ConclusionThrough the limited analysis, AS events could be regarded as reliable prognostic biomarkers for PTC. The splicing correlation network also provided new insight into the potential molecular mechanisms of PTC.

scholarly journals Blood prognostic predictors of treatment response for patients with papillary thyroid cancer

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Xiangxiang Liu ◽  
Zhongke Huang ◽  
Xianghui He ◽  
Xiangqian Zheng ◽  
Qiang Jia ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Poor Prognosis ◽  
Response To Therapy ◽  
Prognostic Indicators ◽  
High Morbidity ◽  
American Thyroid Association ◽  
Papillary Thyroid ◽  
Distribution Width ◽  
Prognosis Group

Abstract Background: Papillary thyroid cancer (PTC) is a very common malignant disease with high morbidity. We needed some pretreatment indicators to help us predict prognosis and guide treatment. We conducted a study about some pretreatment prognostic indicators. Methods: This clinical study recruited 705 postoperative PTC patients (211 males, 494 females). Clinical data before radioactive iodine (RAI) treatment were collected. Patients’ response to therapy were classified into two categories: ‘Good Prognosis Group’ (GPG) and ‘Poor Prognosis Group’ (PPG), according to ‘2015 American Thyroid Association Guidelines’. Differences of indicators between different prognosis groups were compared. Odds ratios (ORs) were calculated by univariate/multiple binary logistic regression models. Difference of body mass index (BMI) changes before and after RAI treatment between different prognosis groups was also compared. Results: A total of 546 (77.45%) belonged to GPG, and 159 (22.55%) belonged to PPG. Platelet (PLT), neutrophil (NEUT), PLT subgroups, and combination of red blood cell distribution width (RDW) and BMI (COR-BMI) were different between two prognosis groups. The significance of the difference between the two groups of BMI disappeared after the Bonferroni correction. PLT and PLT subgroups had detrimental effects on the risk of PPG; T stage had a positive effect on the risk of PPG. PLT subgroup showed a detrimental effect on the risk of PPG when we included additional covariates. Conclusions: We found that lower pretreatment PLT levels may indicate a poor prognosis for PTC. The relationship between platelet-derived growth factor (PDGF) and radiation sensitivity may be the key to this association.

scholarly journals Nomogram-Based New Recurrence Predicting System in Early-Stage Papillary Thyroid Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Yongfeng Ding ◽  
Zhuochao Mao ◽  
Jiaying Ruan ◽  
Xingyun Su ◽  
Linrong Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cox Regression ◽  
Early Stage ◽  
Cox Model ◽  
Staging System ◽  
Papillary Thyroid ◽  
Cox Regression Analysis ◽  
Ajcc Staging

Background and Objectives. The clinicopathological risk factors to predict recurrence of papillary thyroid cancer (PTC) patients remain controversial. Methods. PTC patients treated with thyroidectomy between January 1997 and December 2011 at the First Affiliated Hospital of Zhejiang University (Zhejiang cohort) were included. Multivariate Cox regression analysis was conducted to identify independent recurrence predictors. Then, the nomogram model for predicting probability of recurrence was built. Results. According to Zhejiang cohort (N = 1,697), we found that the 10-year event-free survival (EFS) rates of PTC patients with early-stage (TNM stages I, II, and III) were not well discriminated (91.6%, 89.0%, and 90.7%; P=0.768). The multivariate Cox model identified age, bilaterality, tumor size, and nodal status as independent risk factors for tumor recurrence in PTC patients with TNM stages I–III. We then developed a nomogram with the C-index 0.70 (95% CI, 0.64 to 0.76), which was significantly higher (P<0.0001) than the AJCC staging system (0.52). In the validation group, the C-index remained at a similar level. Conclusions. In this study, we build up a new recurrence predicting system and establish a nomogram for early-stage PTC patients. This prognostic model may better predict individualized outcomes and conduct personalized treatments.

Downregulation of miR-519d-3p is Associated with Poor Outcomes and Facilitates Tumor Progression in Papillary Thyroid Cancer by Regulating FOXQ1

2021 ◽  
Vol 53 (09) ◽  
pp. 625-632
Author(s):  
Pihong Li ◽  
Xiaoyu Pan ◽  
Zhouci Zheng ◽  
Yihan Sun ◽  
Yifan Han ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Progression ◽  
Papillary Thyroid Cancer ◽  
Cox Regression ◽  
Biological Effects ◽  
Pearson Correlation ◽  
Progression Free Survival ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Papillary Thyroid

AbstractMicroRNA-519d-3p (miR-519d-3p) has emerged as a tumor suppressor in several human cancers. But whether miR-519d-3p is involved in papillary thyroid cancer (PTC) remains elusive. In this study, we investigated the potential relevance of miR-miR-519d-3p in PTC. A retrospective study of 119 PTCs was carried out. The RT-qPCR analysis was used to measure the expression of miR-519d-3p and FOXQ1 in PTC tissues and cells. Chi-square test, Kaplan–Meier curve analysis, and multivariate Cox regression analyses were performed to assess the clinical and prognostic value of miR-519d-3p in PTC. Then cellular experiments were used to explore its biological effects on PTC cells. Finally, the Pearson correlation coefficient, dual-luciferase reporter assay, and rescue experiments were used to analyze the association between miR-519d-3p and FOXQ1. miR-519d-3p was significantly downregulated in PTC tissues and cell lines. The decreased expression of miR-519d-3p was associated with reduced overall survival and progression-free survival of patients. The proliferative, migratory, and invasive abilities of cells were blocked or elevated after upregulation or downregulation of miR-519d-3p, while FOXQ1 reversed these cellular behaviors caused after upregulation or knockdown of miR-519d-3p. In conclusion, miR-519d-3p was downregulated in PTC and associated with OS and PFS of patients. MiR-519d-3p may be a tumor-inhibiting miRNA in PTC, and that miR-519d-3p/FOXQ1 axis mediated PTC tumor progression from cell proliferation, migration, and invasion in PTC cells.

scholarly journals Blood-Rich Enhancement in Ultrasonography Predicts Worse Prognosis in Patients With Papillary Thyroid Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Luying Gao ◽  
Xuehua Xi ◽  
Qiong Gao ◽  
Jiajia Tang ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Papillary Thyroid ◽  
Predictive Values ◽  
Incomplete Response ◽  
Potential Association ◽  
Contrast Enhanced ◽  
Patient Prognosis

Contrast-enhanced ultrasound (CEUS) can be used to evaluate microcirculation in cancers, which in turn is associated with the biologic features and ultimately patient prognosis. We conducted a retrospective analysis to examine potential association between CEUS parameters and prognosis in patients with papillary thyroid cancer (PTC). The analysis included 306 patients who underwent CEUS prior to thyroidectomy at our center during a period from 2012 to 2019. Subjects with excellent response (ER) were compared to the non-ER group (including indeterminate response, biochemical incomplete response and structural incomplete response). During the median follow-up of 34 months, ER was observed in 195 (63.7%) subjects. The remaining 111 (36.3%) patients developed non-ER events, with distant metastasis in five (1.6%) cases. In a multivariate COX regression, non-ER event was associated with the male sex (OR = 1.83, 95%CI: 1.21–2.76) and blood-rich enhancement in CEUS (OR = 1.69, 95%CI: 1.04–2.75). Based on this finding, we developed a predictive model: high risk for developing non-ER events was defined as having both risk factors; low risk was defined as having none or only one risk. In receiver operating characteristic (ROC) analysis, the area under the curve was 0.59 (95%CI: 0.52–0.66). The sensitivity and specificity were 17.1 and 95.4%, respectively. The positive and negative predictive values were 67.9 and 66.9%, respectively. In conclusion, blood-rich enhancement in CEUS is associated with non-ER events after thyroidectomy in patients with PTC.

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