Progression Risk Assessment of Post-surgical Papillary Thyroid Carcinoma Based on Circular RNA-Associated Competing Endogenous RNA Mechanisms

Background: Accurate risk assessment of post-surgical progression in papillary thyroid carcinoma (PTC) patients is critical. Exploring key differentially expressed mRNAs (DE-mRNAs) regulated by differentially expressed circular RNAs (circRNAs) via the ceRNA mechanism could help establish a novel assessment tool.Methods: ceRNA network was established based on differentially expressed RNAs and correlation analysis. DE-mRNAs within the ceRNA network associated with progression-free interval (PFI) of PTC were identified to construct a prognostic ceRNA regulatory subnetwork. least absolute shrinkage and selection operator (LASSO)–Cox regression was applied to identify hub DE-mRNAs and establish a novel DE-mRNA signature in predicting PFI of PTC.Results: Six hub DE-mRNAs, namely, CLCNKB, FXBO27, FXYD6, RIMS2, SPC24, and CDKN2A, were identified to be most significantly related to the PFI of PTC, and a prognostic DE-mRNA signature was proposed. A nomogram incorporating the DE-mRNA signature and clinical parameters was established to improve the progression risk assessment in post-surgical PTC, which was superior to the American Thyroid Association risk stratification system and distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size (MACIS) score American Joint Committee on Cancer staging system.Conclusions: Based on the circRNA-associated ceRNA RNA mechanism, a DE-mRNA signature and prognostic nomogram was established, which may improve the progression risk assessment in post-surgical PTC.

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Progression Risk Assessment of Post-Surgical Papillary Thyroid Carcinoma Based on Circular RNA-Associated Competing Endogenous RNA Mechanisms

10.21203/rs.3.rs-47878/v1 ◽

2020 ◽

Author(s):

Mengwei Wu ◽

Rui Liu ◽

Hongwei Yuan ◽

Xiequn Xu ◽

Xiaobin Li ◽

...

Keyword(s):

Risk Assessment ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Assessment Tool ◽

Cox Regression ◽

Circular Rna ◽

Differentially Expressed ◽

Papillary Thyroid ◽

Progression Risk ◽

Stratification System

Abstract BackgroundAccurate risk assessment of post-surgical progression in papillary thyroid carcinoma (PTC) patients is critical. Exploring key differentially expressed mRNAs (DE-mRNAs) regulated by differentially expressed circRNAs (DE-circRNAs) via the ceRNA mechanism could help establish a novel assessment tool. MethodsceRNA network was established based on differentially expressed RNAs and correlation analysis. DE-mRNAs within the ceRNA network associated with progression-free interval (PFI) of PTC were identified to construct a prognostic ceRNA regulatory subnetwork. LASSO-Cox regression was applied to identify hub DE-mRNAs and establish a novel DE-mRNA signature in predicting PFI of PTC.ResultsSix hub DE-mRNAs, namely CLCNKB, FXBO27, FXYD6, RIMS2, SPC24, and CDKN2A, were identified to be most significantly related to the PFI of PTC and a prognostic DE-mRNA signature was proposed. A nomogram incorporating the DE-mRNA signature and clinical parameters was established to improve the progression risk assessment in post-surgical PTC, which was superior to the ATA risk stratification system and MACIS score AJCC staging system.ConclusionsBased on the circRNA-associated ceRNA RNA mechanism, a DE-mRNA signature and prognostic nomogram was established, which may improve the progression risk assessment in post-surgical PTC.

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Identification and validation of an immune-related prognostic signature and key gene in papillary thyroid carcinoma

Cancer Cell International ◽

10.1186/s12935-021-02066-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Rujia Qin ◽

Chunyan Li ◽

Xuemin Wang ◽

Zhaoming Zhong ◽

Chuanzheng Sun

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Cox Regression ◽

Expression Profiles ◽

Tumor Therapy ◽

Differentially Expressed ◽

Expression Level ◽

Papillary Thyroid ◽

Ppi Network ◽

Immune Activity

Abstract Background Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. The effect of traditional anti-tumor therapy is not ideal for the patients with recurrence, metastasis and radioiodine resistance. The abnormal expression of immune-related genes (IRGs) has critical roles in the etiology of PTC. However, the effect of IRGs on PTC prognosis remains unclear. Methods Based on The Cancer Genome Atlas (TCGA) and ImmPort databases, we integrated IRG expression profiles and progression-free intervals (PFIs) of PTC patients. First, we identified the differentially expressed IRGs and transcription factors (TFs) in PTC. Subsequently, an IRG model that can predict the PFI was constructed by using univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses of the differentially expressed IRGs in the TCGA. Additionally, a protein–protein interaction (PPI) network showed the interactions between the differentially expressed genes (DEGs), and the top 30 genes with the highest degree were extracted from the network. Then, the key IRG was identified by the intersection analysis of the PPI network and univariate Cox regression, which was verified the differential expression of by western blotting and immunohistochemistry (IHC). ssGSEA was performed to understand the correlation between the key IRG expression level and immune activity. Results A total of 355 differentially expressed IRGs and 43 differentially expressed TFs were identified in PTC patients. Then, eight IRGs were finally utilized to construct an IRG model. The respective areas under the curve (AUCs) of the IRG model reached 0.948, 0.820, and 0.831 at 1, 3 and 5 years in the training set. In addition, lactotransferrin (LTF) was determined as the key IRG related to prognosis. The expression level of LTF in tumor tissues was significantly lower than that in normal tissues. And the results of ssGSEA showed the expression level of LTF is closely related to immune activity. Conclusions These findings show that the prognostic model and key IRG may become promising molecular markers for the prognosis of PTC patients.

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Identification of an Autophagy-Related Signature Predicting Overall Survival for Papillary Thyroid Carcinoma

Dose-Response ◽

10.1177/1559325819899265 ◽

2020 ◽

Vol 18 (1) ◽

pp. 155932581989926 ◽

Cited By ~ 1

Author(s):

Gang Hu ◽

Hong-fang Feng ◽

Hui Zhan

Keyword(s):

Overall Survival ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Scoring System ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Papillary Thyroid ◽

Cox Regression Analysis

Background: Papillary thyroid carcinoma usually shows an excellent prognosis. However, its recurrence or persistence rate is high. In this study, we used bioinformatics to identify autophagy-related genes (ARGs) and establish a novel scoring system for papillary thyroid carcinoma. Methods: We collected ARGs sequencing data of patients with papillary thyroid carcinoma from The Cancer Genome Atlas database. Differentially expressed ARGs were identified by the “Limma” package in R language. After univariate and multivariate Cox regression analysis, an ARG signature was developed. The established prognostic signature was evaluated by Kaplan-Meier curve and time-dependent receiver operating characteristic. Results: A sum of 26 differentially expressed ARGs were identified. Gene set enrichment analysis revealed that several significantly oncological signatures were enriched, such as autophagy, p53 signaling pathway, apoptosis, human cytomegalovirus infection, and platinum drug resistance. After univariate and multivariate analysis, 3 ARGs ( ITPR1, CCL2, and CDKN2A) were selected to develop autophagy-related signature. Patients with high risk had significantly shorter overall survival than those with low risk. The areas under the curve indicated that the signature showed good accuracy of prediction. Conclusions: We established a novel scoring system based on 3 ARGs, which provides a promising tool for the development of personalized therapy.

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lncRNA-miRNA-mRNA ceRNA Network in Thyroid Carcinoma from The Cancer Genome Atlas

10.21203/rs.3.rs-41546/v1 ◽

2020 ◽

Author(s):

Guoheng Mo ◽

Qunguang Jiang ◽

Zixuan Wang ◽

Zhaoting Zheng ◽

XiaoSi Chen

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Molecular Mechanisms ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Papillary Thyroid ◽

Cerna Network ◽

Cancer Genome Atlas ◽

Genome Atlas

Abstract Increasing evidence indicates that the competitive endogenous RNA (ceRNA) hypothesis, that is, long non-coding RNA (LncRNA) can competitively bind microRNA (miRNA) through miRNA response elements to affect the expression of target RNA, and dysregulation of LncRNA expression plays a key role in tumor progression. The papillary thyroid carcinoma that we studied is the most significant pathological type of thyroid cancer, but its ceRNA network has not been extensively evaluated. We analyzed level-3 data from RNA-Seq of 58 para-carcinoma tissues and 501 patients with primary papillary thyroid carcinoma (PTC) using the DEseq software package and downloaded clinical information from The Cancer Genome Atlas (TCGA) to find potential biomarkers or therapeutic targets. As a result, 149 differential miRNAs were selected, including 117 up -regulated, 32 down-regulated, and 3099 differential mRNAs, including 1976 up-regulated, 1123 down-regulated, and 434 differential lncRNAs, including 331 up-regulated and 103 down-regulated (Fold Change > 2, P < 0.05). The interactions between these differentially expressed RNA groups constitute the ceRNA network of PTC. Moreover, we used the microde database to predict the miRNAs that may be acted by the above screened differential lncRNAs and intersected with the selected miRNAs, and further predicted the target genes of the intersecting miRNAs by TargetScan, miRTarBase and miRDB, and intersected with the selected mRNAs. From the constructed ceRNA network we can see that Linc00460 may cause the invasion and metastasis of PTC by competitively inhibiting hsa-mir-150 and upregulating the expression of its downstream target gene EREG. Our study identified a series of lncRNAs associated with PTC progression and prognosis, and this complex ceRNA interaction network provides guidance for better understanding of the molecular mechanisms of PTC and can be used as an effective diagnostic tool for PTC invasion, metastasis and prognosis. Kaplan-Meier analysis of the differentially expressed RNAs associated with PTC pathogenesis confirmed that the lncRNAs AC097717.1, C20orf203, EMX2OS were potentially associated with the prognosis of PTC (P<0.05).

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Identification of Differentially Expressed Genes Associated with Papillary Thyroid Carcinoma

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200402085832 ◽

2020 ◽

Vol 23 (6) ◽

pp. 546-553

Author(s):

Hongyuan Cui ◽

Mingwei Zhu ◽

Junhua Zhang ◽

Wenqin Li ◽

Lihui Zou ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Cellular Proliferation ◽

Mrna Level ◽

Thyroid Tissue ◽

Differentially Expressed ◽

Thyroid Tumors ◽

Papillary Thyroid

Objective: Next-generation sequencing (NGS) was performed to identify genes that were differentially expressed between normal thyroid tissue and papillary thyroid carcinoma (PTC). Materials & Methods: Six candidate genes were selected and further confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry in samples from 24 fresh thyroid tumors and adjacent normal tissues. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to investigate signal transduction pathways of the differentially expressed genes. Results: In total, 1690 genes were differentially expressed between samples from patients with PTC and the adjacent normal tissue. Among these, SFRP4, ZNF90, and DCN were the top three upregulated genes, whereas KIRREL3, TRIM36, and GABBR2 were downregulated with the smallest p values. Several pathways were associated with the differentially expressed genes and involved in cellular proliferation, cell migration, and endocrine system tumor progression, which may contribute to the pathogenesis of PTC. Upregulation of SFRP4, ZNF90, and DCN at the mRNA level was further validated with RT-PCR, and DCN expression was further confirmed with immunostaining of PTC samples. Conclusion: These results provide new insights into the molecular mechanisms of PTC. Identification of differentially expressed genes should not only improve the tumor signature for thyroid tumors as a diagnostic biomarker but also reveal potential targets for thyroid tumor treatment.

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Predictors of thyroglobulin in the lymph nodes recurrence of papillary thyroid carcinoma undergoing total thyroidectomy

BMC Surgery ◽

10.1186/s12893-021-01063-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhichao Xing ◽

Yuxuan Qiu ◽

Zhe Li ◽

Lingyun Zhang ◽

Yuan Fei ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Lymph Nodes ◽

Total Thyroidectomy ◽

Radioactive Iodine ◽

Independent Predictor ◽

Central Neck Dissection ◽

American Thyroid Association ◽

Papillary Thyroid ◽

Serum Thyroglobulin

Abstract Background To investigate the association between postoperative lymph nodes (LNs) recurrence and distinct serum thyroglobulin (Tg) levels in patients with papillary thyroid carcinoma (PTC). Methods This study included PTC patients who underwent total thyroidectomy (TT) with at least central neck dissection and then re-operated due to recurrence of LNs between January 2013 and June 2018. These patients were grouped by negative or positive serum Tg levels according to the American Thyroid Association guidelines. Results Of the 60 included patients, 49 underwent radioactive iodine (RAI) treatment. Maximum unstimulated Tg (uTg) ≥ 0.2 ng/mL were associated with larger diameter of recurrent LNs (P = 0.027), and higher rate of metastatic LNs (P < 0.001). Serum-stimulated Tg (off-Tg) ≥ 1 ng/mL (P = 0.047) and unstimulated Tg (on-Tg) ≥ 0.2 ng/Ml (P = 0.013) were associated with larger diameter of recurrent LNs. Number of metastatic LNs ≥ 8 was an independent predictor for postoperative maximum uTg ≥ 0.2 ng/mL (OR = 8.767; 95% CI = 1.392–55.216; P = 0.021). Ratio of metastatic LNs ≥ 25% was an independent predictor for off-Tg ≥ 1 ng/mL (OR = 20.997; 95% CI = 1.649–267.384; P = 0.019). Conclusion Postoperative Tg-positive status was associated with larger size of recurrent LNs. Number of metastatic LNs ≥ 8 and ratio of metastatic LNs ≥ 25% were independent predicators for uTg-positive and off-Tg-positive status, respectively.

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Tall cell percentage alone in PTC without aggressive features should not guide patients' clinical management

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab388 ◽

2021 ◽

Author(s):

Anello Marcello Poma ◽

David Viola ◽

Elisabetta Macerola ◽

Agnese Proietti ◽

Eleonora Molinaro ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Low Risk ◽

World Health ◽

American Thyroid Association ◽

Papillary Thyroid ◽

Cell Percentage ◽

Tall Cell ◽

Definition Of ◽

The Impact

Abstract Purpose Recent diagnostic criteria updates of the tall cell variant of papillary thyroid carcinoma (TCPTC) by the World Health Organization (WHO) have determined the inclusion of tumours with 30-49% of tall cells. However, the impact of tall cell percentage on papillary thyroid carcinoma (PTC) patients’ prognosis is still debated. We aimed to evaluate whether tall cell percentage affects patients’ outcome in the absence of aggressive features. Methods Rates of aggressive features, recurrence-free survival (RFS) and distant RFS (DRFS) (5-year median follow-up) were compared among tumours with less than 30%, 30-49% and at least 50% of tall cells. We also evaluated the impact of the new tall cell cut-off on patient management. Results Overall, 3092 tumours (15.7% of all PTC) were collected: 792 PTC had less than 30%, 503 had 30-49%, and 1797 had 50% or more tall cell areas. With the new definition of WHO, the number of TCPTC increased by 28%. There were no differences in recurrence rates according to tall cell percentage. The coexistence of BRAF and TERT promoter mutations predicted a worse RFS. Considering the new definition of TCPTC, the level of risk according to the American Thyroid Association increased from low to intermediate in 4.2% of cases. However, the recurrence rate within this subgroup was comparable to low-risk. Conclusions TCPTC and PTC with tall cell areas can be considered as a unique group with similar recurrence risk. However, whenever aggressive features are absent, tumors have a low risk of recurrence independently of tall cell percentage.

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IMMUNOHISTOCHEMICAL RISK ASSESSMENT OF THE LYMPHOGENOUS METASTASIS OF PAPILLARY THYROID CARCINOMA

Journal of the Grodno State Medical University ◽

10.25298/2221-8785-2018-16-6-661-665 ◽

2018 ◽

Vol 16 (6) ◽

pp. 661-665

Author(s):

К. M. Butolina ◽

◽

Т. Т. Shtabinskaya ◽

V. А. Basinsky ◽

S. А. Lyalikov ◽

...

Keyword(s):

Risk Assessment ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Papillary Thyroid ◽

Lymphogenous Metastasis

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CircLDLR Promotes Papillary Thyroid Carcinoma Tumorigenicity by Regulating miR-637/LMO4 Axis

Disease Markers ◽

10.1155/2021/3977189 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yuan-ming Jiang ◽

Wei Liu ◽

Ling Jiang ◽

Hongbin Chang

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Migration And Invasion ◽

Circular Rnas ◽

Papillary Thyroid ◽

Induced Apoptosis

Background. Circular RNAs (circRNAs) have been reported to play important roles in the development and progression of papillary thyroid carcinoma (PTC). However, the function and molecular mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the tumorigenesis of PTC remain unknown. Results. In this study, circLDLR was found to be markedly upregulated in PTC tissues and cell lines, and knockdown of circLDLR inhibited PTC cell proliferation, migration, and invasion but induced apoptosis in vitro. Moreover, circLDLR acted as a sponge for miR-637, and miR-637 interference reversed the anticancer effects of circLDLR knockdown on PTC cells. LMO4 was verified to be a target of miR-637; LMO4 upregulation abolished miR-637 mediated inhibition of cell growth and metastasis in PTC. Additionally, circLDLR could indirectly modulate LMO4 via acting as a sponge of miR-637 in PTC cells. Besides that, xenograft analysis showed that circLDLR knockdown suppressed tumor growth in vivo via regulating LMO4 and miR-637. Conclusion. Taken together, these results demonstrated that circLDLR promoted PTC tumorigenesis through miR-637/LMO4 axis, which may provide a novel insight into the understanding of PTC tumorigenesis and be useful in developing potential targets for PTC treatment.

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INCIDENTAL PULMONARY METASTASES REVEALING SUBCENTIMETER PAPILLARY THYROID CARCINOMA

AACE Clinical Case Reports ◽

10.4158/accr-2020-0051 ◽

2020 ◽

Vol 6 (5) ◽

pp. e273-e278

Author(s):

Ruey Hu ◽

George Xu ◽

Thomas Stricker ◽

Bingshan Li ◽

Vivian L. Weiss ◽

...

Keyword(s):

Computed Tomography ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Active Surveillance ◽

Thyroid Nodules ◽

Lung Metastases ◽

Molecular Testing ◽

American Thyroid Association ◽

Cancer Genes ◽

Papillary Thyroid

Objective: Here we present 2 cases of papillary thyroid microcarcinomas (PMCs) that had metastasized at presentation. The 2015 American Thyroid Association and the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) criteria do not recommend biopsy of the majority of subcentimeter thyroid nodules, as PMCs are mostly indolent with excellent prognosis. However, the paradigm of active surveillance presents a conundrum on how to identify the rare patient with distant metastatic disease while avoiding unnecessary intervention in the majority. Methods: After initial discovery of incidental lesions on chest computed tomography, core or wedge biopsies of the lung lesion were performed. Thyroid nodules on ultrasound were classified by TI-RADS. Tumor DNA was sequenced, annotated, filtered on 119 known cancer genes, and filtered for variants with an exome allele frequency of <0.001. Results: A 70-year-old woman and a 29-year-old woman presented with incidental pulmonary lesions on computed tomography scan. Lung biopsy revealed lung metastases from papillary thyroid carcinoma. The thyroid nodules in both patients were TI-RADS 3 and American Thyroid Association low-suspicion. Molecular testing showed a c.1721C>G mutation (p.Thr574Ser) in the TSHR gene in patient 1 and a codon 61 mutation in the NRAS gene in patient 2. Both patients were iodine-avid, with complete structural remission in one patient and ongoing treatment with evidence of structural response in the other. Conclusion: The 2 presentations demonstrate unexpected and concerning behavior of PMCs. Both thyroid tumors were subcentimeter in diameter, meaning they would have escaped detection using traditional risk-stratification algorithms in active surveillance. Further knowledge of tumor genetics and microenvironment may assist in predicting tumor behavior in PMCs.

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