scholarly journals Loss of ZNF677 Expression Is an Independent Predictor for Distant Metastasis in Middle Eastern Papillary Thyroid Carcinoma Patients

2021 ◽  
Vol 22 (15) ◽  
pp. 7833
Author(s):  
Abdul K. Siraj ◽  
Pratheesh Kumar Poyil ◽  
Sandeep Kumar Parvathareddy ◽  
Khadija Alobaisi ◽  
Saeeda O. Ahmed ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Distant Metastasis ◽  
Zinc Finger Protein ◽  
Independent Predictor ◽  
Middle Eastern ◽  
Distant Metastases ◽  
Papillary Thyroid ◽  
Finger Protein

Thyroid cancer incidence has increased in recent decades. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Approximately 30% of PTC patients develop recurrence or distant metastasis and tend to have poor prognosis. Therefore, the identification of targetable biomarkers in this subset of patients is of great importance. Accumulating evidence indicates that zinc finger protein 677 (ZNF677), which belongs to the zinc finger protein family, is an important effector during the progression of multiple malignancies. However, its role in Middle Eastern PTC patients has not been fully illustrated. Here, we uncovered the molecular mechanism and the clinical impact of ZNF677 expression in a large cohort of more than 1200 Middle Eastern PTC and 15 metastatic tissues. We demonstrated that ZNF677 is frequently downregulated in primary PTC (13.6%, 168/1235) and showed that complete loss of expression of ZNF677 is significantly associated with aggressive clinico-pathological markers such as extrathyroidal extension (p = 0.0008) and distant metastases (p < 0.0001). We also found a significantly higher incidence of ZNF677 loss in primary tumors with distant metastases (33.3%; p < 0.0001) as well as in distant metastatic tissues (46.7%; p = 0.0002) compared to the overall cohort (13.6%). More importantly, PTC with loss of ZNF677 expression showed significantly lower metastasis-free survival (p = 0.0090). Interestingly, on multivariate logistic regression analysis, ZNF677 loss was an independent predictor of distant metastasis in PTC (Odds ratio = 2.60, 95% Confidence interval = 1.20–5.62, p = 0.0155). In addition, we found a significant association between ZNF677 loss and phospho-AKT expression (p < 0.0001). Our functional molecular results suggest that ZNF677 acts as a tumor suppressor, mediating its effect by inhibiting AKT phosphorylation. Taken together, our results highlight the pivotal role played by ZNF677 during carcinogenesis and metastasis formation in Middle Eastern PTC patients.

scholarly journals Solitary Liver Metastasis from Follicular Variant Papillary Thyroid Carcinoma: A Case Report

2021 ◽  
Vol 22 (2) ◽  
pp. 146-149
Author(s):  
Rahima Perveen ◽  
Jasmin Ferdous ◽  
Sharmin Quddus ◽  
Tapati Mandal
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Distant Metastases ◽  
Differentiated Thyroid Carcinoma ◽  
Papillary Thyroid ◽  
Follicular Variant ◽  
Thyroid Carcinomas ◽  
Visceral Metastases ◽  
Solitary Liver

Papillary and follicular thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Distant metastases are rare events at the onset of DTC. Sites of metastases from follicular thyroid cancer (FTC) are usually osseous, and those from papillary thyroid cancer (PTC) metastasize to regional nodal basins and the lungs. Visceral metastases are rare, but the involvement of multiple sites has been reported so far. Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare.We present the case of a patient with follicular variant of papillary thyroid carcinoma (FVPTC) unusually involving the liver. Bangladesh J. Nuclear Med. 22(2): 146-149, Jul 2019

Abstract LBA042: Male Sex is an Independent Predictor of Recurrence-Free Survival in Middle Eastern Papillary Thyroid Carcinoma

2021 ◽  
Author(s):  
KHAWLA S. AL-KURAYA ◽  
Sandeep Kumar Parvathareddy ◽  
Abdul K Siraj ◽  
Felisa De Vera ◽  
Padmanaban Annaiyappanaidu ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Independent Predictor ◽  
Middle Eastern ◽  
Recurrence Free Survival ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Male Sex

scholarly journals Papillary Thyroid Carcinoma with Malignant Pleural Effusion: Dilemma of Etiology

2010 ◽  
Vol 1 (2) ◽  
pp. 117-119 ◽  
Author(s):  
Arvind Krishnamurthy ◽  
KT Siddappa
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Pleural Effusion ◽  
Thyroid Carcinoma ◽  
Distant Metastasis ◽  
Malignant Pleural Effusion ◽  
Standard Treatment ◽  
Pleural Cavity ◽  
Published Data ◽  
Papillary Thyroid

Abstract Papillary carcinomas of thyroid generally have an indolent course with metastatic disease in less than 5% of patients. Common sites of distant metastasis include lung and bone. A presentation with malignant pleural effusion is exceedingly rare with only a handful of cases reported in literature. We present a case and discuss the treatment of a patient presenting of papillary thyroid cancer with a relapse of the disease in the pleural cavity. There are no standard treatment recommendations in this setting in view of paucity of published data from literature.

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

BMC Surgery ◽  
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.

Assessment of Biomarkers for Clinical Diagnosis of Papillary Thyroid Carcinoma with Distant Metastasis

2010 ◽  
Vol 25 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Huasheng Liang ◽  
Yuhua Zhong ◽  
Zuojie Luo ◽  
Yu Huang ◽  
Huade Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Clinical Diagnosis ◽  
Distant Metastasis ◽  
Roc Curve ◽  
Curve Analysis ◽  
Papillary Thyroid ◽  
Roc Curve Analysis ◽  
Thyroid Carcinomas

Early diagnosis and treatment of thyroid cancers are critical for better prognosis and better survival rates. The purpose of this study was to identify potential diagnostic markers for papillary thyroid carcinomas with distant metastasis. Fifty-eight papillary thyroid tumor specimens (27 papillary thyroid carcinomas with distant metastasis and 31 without metastasis) were examined, and protein expression of pituitary tumor-transforming gene (PTTG), E-cadherin, p27kip1, vascular endothelial growth factor (VEGF)-C, metalloproteinase (MMP) 2, MMP9, chemokine receptor CXCR4, and basic fibroblast growth factor (bFGF) in these tumors was assessed by immunohistochemistry. The clinicopathological variables with diagnostic significance were determined by multivariate analysis, and their diagnostic values were evaluated by ROC curve analysis. PTTG, VEGF-C, MMP2, MMP9, CXCR4, and bFGF were overexpressed in metastatic papillary thyroid carcinomas, whereas p27kip1 expression was elevated only in carcinomas lacking metastasis. Multiple-factor binary ordinal logistic regression analysis revealed that PTTG, VEGF-C, MMP2, and bFGF were independently related to biological metastatic behavior in thyroid tumors, suggesting their potential use as biomarkers. ROC curve analysis showed that among these four proteins, VEGF-C and bFGF were the best diagnostic biomarkers. A VEGF-C and bFGF cluster was the most useful factor for the differential diagnosis between metastatic and non-metastatic papillary thyroid cancers. Thus, the combined use of VEGF-C and bFGF as biomarkers may improve the diagnostic accuracy of papillary thyroid carcinoma and may be useful in multimodal screening programs for the clinical diagnosis of papillary thyroid carcinoma and early detection of papillary thyroid carcinoma with distant metastasis.

scholarly journals SUN-132 KLF5 Is a Poor Prognostic Marker and Therapeutic Target for Middle Eastern Papillary Thyroid Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Khawla S Al-Kuraya ◽  
Abdul K Siraj ◽  
Pratheeshkumar Poyil ◽  
Divya Padmaja ◽  
Sandeep Kumar Parvathareddy ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Critical Role ◽  
Dependent Manner ◽  
Papillary Thyroid ◽  
Inhibition Of Proliferation ◽  
Over Expression

Abstract Thyroid cancer is the second most common malignancy among females in Saudi Arabia, with Papillary thyroid carcinoma (PTC) accounting for 80-90%. The Kruppel-like factor 5 (Klf5) is a transcription factor that play a critical role in cell transformation, proliferation and oncogenesis. Immunohistochemical analysis of KLF5 was performed in 1219 PTC cases. KLF5 over-expression was noted in 65.1% (793/1219) of PTCs, and was significantly associated with tall-cell variant (p &lt;0.0001), extrathyroidal extension (p = 0.0003), lymph node metastasis (p &lt; 0.0001) and stage IV tumors (p &lt; 0.0001). Significant association was also noted with HIF-1α over-expression (p = 0.0492). Interestingly, KLF5 over-expressing tumors showed poor disease-free survival (p = 0.0066). Functional studies in PTC cell lines showed that KLF5 co-immunoprecipitated with HIF-1α. Knockdown of KLF5 decreased the expression of HIF-1α while KLF5 was not affected by HIF-1α inhibition, suggesting that KLF5 is a functional upstream of HIF-1α. Down-regulation of KLF5 using specific inhibitor, ML264 or siRNA inhibited cell invasion and migration. In addition, treatment of PTC cell lines with ML264 resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner. Furthermore, silencing of KLF5 significantly decreased the self-renewal ability of spheroids generated from PTC cells. Our findings confer that KLF5 may be a potential therapeutic target for the treatment of papillary thyroid cancer.

scholarly journals Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weilin Pu ◽  
Xiao Shi ◽  
Pengcheng Yu ◽  
Meiying Zhang ◽  
Zhiyan Liu ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Single Cell ◽  
Epithelial Mesenchymal Transition ◽  
Distant Metastases ◽  
Developmental Trajectory ◽  
Papillary Thyroid ◽  
Normal Morphology ◽  
Mesenchymal Transition ◽  
Therapeutic Implications

AbstractThe tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications.

scholarly journals SUN-416 Fatigue and Quality of Life Among Thyroid Cancer Survivors

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Maki Yukari
Keyword(s):  
Quality Of Life ◽  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cancer Survivors ◽  
Papillary Thyroid ◽  
Explanatory Variables ◽  
Initial Surgery ◽  
Sf 36

Abstract BACKGROUND Fatigue among thyroid cancer survivors is an important issue that needs to be appreciated and managed appropriately. Although several studies have reported potential factors that might be related to postoperative fatigue, the associations have yet to be inconclusive. The purpose of the present study was to estimate the prevalence of clinical fatigue in patients with papillary thyroid carcinoma and to reveal predictive factors, including their quality of life. METHODS A cross-sectional survey was conducted on patients with papillary thyroid carcinoma. Patients who underwent non-curative surgery, or those with recurrent or metastatic PTC, or those with other malignancies were excluded. The primary outcome was fatigue measured by the Cancer Fatigue Scale (CFS), and the secondary outcome was quality of life (QoL) quantified using the SF-36 v2. The following explanatory variables were collected; gender, age, employment status, marital status, co-morbidities, time since initial surgery, types of surgery, replacement of thyroid hormone, use of radioactive iodine, and the level of thyrotropin. The prevalence of clinical fatigue was estimated with the cut-off value of 18/19 of the CFS score. Correlations between the CFS score and the explanatory variables were examined using uni-variable analyses as well as multi-variable analysis. RESULTS Three hundred twenty-one patients participated in the survey. Of them, 258 respondents (80%) were female. The median age was 58 years, and the median time from initial surgery was 6.4 years. The mean and the standard deviation of the CFS score were 17.9 and 9.3, respectively (range: 0-48). The prevalence of clinical fatigue was 42% [95%CI: 36-47%]. Among the variables explored, having a job and scores of the mental component summary, the physical component summary, and the role/social component summary of the SF-36 were inversely associated with the CFS score in both uni- and multivariable analyses. CONCLUSION Postoperative fatigue was common in thyroid cancer survivors. Patients with a job and better QoL, in particular, those with good mental health, maybe at low-risk of developing the burden.

scholarly journals Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

2020 ◽  
Author(s):  
Dumitru A Iacobas
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Mathematical Object ◽  
Human Thyroid ◽  
Expression Data ◽  
Papillary Thyroid ◽  
Hormone Synthesis ◽  
Apoptosis Pathways ◽  
Thyroid Cancer Cell Lines

Publically available (own) transcriptomic data were re-analyzed to quantify the alteration of functional pathways in the thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data were generated from one case of papillary thyroid carcinoma (PTC) and from genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric perspective that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase of the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that its experimental overexpression may force the PTC cells into apoptosis with negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cells before and after lentiviral transfection with DDX19B.

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