-
1.
Systems biomarkers for papillary thyroid cancer prognosis and treatment through multi-omics networks.
Gulfidan, G, Soylu, M, Demirel, D, Erdonmez, HBC, Beklen, H, Ozbek Sarica, P, Arga, KY, Turanli, B
Archives of biochemistry and biophysics. 2022;:109085
Abstract
The identification of biomolecules associated with papillary thyroid cancer (PTC) has upmost importance for the elucidation of the disease mechanism and the development of effective diagnostic and treatment strategies. Despite particular findings in this regard, a holistic analysis encompassing molecular data from different biological levels has been lacking. In the present study, a meta-analysis of four transcriptome datasets was performed to identify gene expression signatures in PTC, and reporter molecules were determined by mapping gene expression data onto three major cellular networks, i.e., transcriptional regulatory, protein-protein interaction, and metabolic networks. We identified 282 common genes that were differentially expressed in all PTC datasets. In addition, six proteins (FYN, JUN, LYN, PML, SIN3A, and RARA), two Erb-B2 receptors (ERBB2 and ERBB4), two cyclin-dependent receptors (CDK1 and CDK2), and three histone deacetylase receptors (HDAC1, HDAC2, and HDAC3) came into prominence as proteomic signatures in addition to several metabolites including lactaldehyde and proline at the metabolome level. Significant associations with calcium and MAPK signaling pathways and transcriptional and post-transcriptional activities of 12 TFs and 110 miRNAs were also observed at the regulatory level. Among them, six miRNAs (miR-30b-3p, miR-15b-5p, let-7a-5p, miR-130b-3p, miR-424-5p, and miR-193b-3p) were associated with PTC for the first time in the literature, and the expression levels of miR-30b-3p, miR-15b-5p, and let-7a-5p were found to be predictive of disease prognosis. Drug repositioning and molecular docking simulations revealed that 5 drugs (prochlorperazine, meclizine, rottlerin, cephaeline, and tretinoin) may be useful in the treatment of PTC. Consequently, we report here biomolecule candidates that may be considered as prognostic biomarkers or potential therapeutic targets for further experimental and clinical trials for PTC.
-
2.
High prevalence of thyroid carcinoma in patients with insulin resistance: a meta-analysis of case-control studies.
Zhao, J, Zhang, Q, Yang, Y, Yao, J, Liao, L, Dong, J
Aging. 2021;(18):22232-22241
Abstract
The association between insulin resistance and thyroid carcinoma is controversial. We conducted this meta-analysis of association between insulin resistance and thyroid carcinoma. There were 14 studies included in this meta-analysis. Random-effect model was used to merge the weighted mean difference value of fasting serum insulin level and the pooled effect shows that the level of fasting serum insulin is higher in patients with thyroid carcinoma than those of controls (1.88, 95% CI 0.87 to 2.90, P=0.0003). Random-effect model was used to estimate the pooled weighted mean difference and it shows that thyroid carcinoma patients have a higher level of homeostasis model assessment of insulin resistance (HOMA-IR) than patients without thyroid carcinoma (0.54, 95% CI 0.29 to 0.78, P<0.0001). Fixed-effect model with the odds ratio of insulin resistance shows that insulin resistance could increase the risk of thyroid carcinoma 216% compared with participants without insulin resistance (3.16, 95% CI 2.09 to 4.77, P<0.0001). In conclusion, insulin resistance might be a risk factor for thyroid carcinoma.
-
3.
Association between programmed cell death ligand 1 expression and thyroid cancer: A meta-analysis.
Wan, B, Deng, P, Dai, W, Wang, P, Dong, Z, Yang, C, Tian, J, Hu, T, Yan, K
Medicine. 2021;(14):e25315
-
-
Free full text
-
Abstract
BACKGROUND Programmed cell death ligand 1 (PD-L1), which is highly expressed in a variety of malignant tumors, is closely related to clinicopathological features and prognosis. However, there are few studies on the potential effects of PD-L1 on thyroid carcinoma, the incidence of which has shown an upward trend worldwide. This study aimed to explore the association between PD-L1 expression and clinicopathological features and prognosis of thyroid cancer. METHODS An elaborate retrieval was performed using Medline, PubMed, Cochrane Library, EMBASE, Web of Science, WanFang databases, and China National Knowledge Infrastructure to determine the association between PD-L1 expression and disease-free survival (DFS), overall survival (OS), and clinicopathological features in patients with thyroid cancer. Study selection, data extraction, risk assessment, and data synthesis were performed independently by 2 reviewers. In this meta-analysis, RevMan 5.3 and Stata 15.1 were used for bias risk assessment and data synthesis. RESULTS After a detailed search, 2546 cases reported in 13 articles were included in this meta-analysis. The outcomes revealed that high expression of PD-L1 in patients with thyroid cancer was associated with poor DFS (hazard ratio [HR] = 3.37, 95% confidence interval [CI] 2.54-4.48, P < .00001) and OS (HR = 2.52, 95% CI: 1.20-5.32, P = .01). High PD-L1 expression was associated with tumor size ≥2 cm, tumor recurrence, extrathyroidal extension, concurrent thyroiditis, unifocal tumor, and absence of psammoma body (P < .05). Subgroup analysis showed that positive expression of PD-L1 was related to poor prognosis for DFS of non-medullary thyroid carcinoma, and the overexpression of PD-L1 in differentiated thyroid carcinoma (DTC) was related to tumor recurrence, concurrent thyroiditis, extrathyroidal extension, unifocal DTC, late stage DTC, and BRAFV600E mutation in DTC. CONCLUSION PD-L1 is a significant predictor of prognosis and malignancy of thyroid cancer (especially DTC), and PD-L1 inhibitors may be a promising therapeutic option for refractory thyroid cancer in the future.
-
4.
A dose-response meta-analysis of coffee consumption and thyroid cancer occurrence.
Shao, CC, Luo, D, Pang, GD, Xiao, J, Yang, XR, Zhang, Y, Jia, HY
International journal of food sciences and nutrition. 2020;(2):176-185
Abstract
The relationship between coffee consumption and thyroid cancer (TC) occurrence has been evaluated in several observational studies with controversial results. The study aims to examine the associations between coffee consumption and TC occurrence. Systematic searches up to February 2019 were conducted. We estimated summary adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs). The dose-response analysis was conducted by using generalised least square trend estimation. A total of ten studies involving 379,825 participants and 1,254 TC cases were included. The total summary RR showed that high coffee consumption was a protection factor of TC (RR = 0.75; 95% CI, 0.62-0.91). With the linear cubic spline model, the occurrence of TC was reduced by 5% with each one cup/day increment of coffee consumption (RR = 0.95; 95% CI, 0.91-0.99).This meta-analysis provides quantitative evidence that coffee consumption was inversely associated with the TC occurrence in a linear dose-response manner.
-
5.
Comparative efficacy and safety of tyrosine kinase inhibitors for thyroid cancer: a systematic review and meta-analysis.
Oba, T, Chino, T, Soma, A, Shimizu, T, Ono, M, Ito, T, Kanai, T, Maeno, K, Ito, KI
Endocrine journal. 2020;(12):1215-1226
-
-
Free full text
-
Abstract
The tyrosine kinase inhibitors (TKIs) sorafenib, lenvatinib, vandetanib, and cabozantinib are currently used for thyroid cancer treatment; however, the differences in their clinical efficacy and toxicity remain unclear. This meta-analysis assessed the efficacy and toxicity of these four TKIs based on 34 studies. The pooled incidence of partial response (PR), stable disease (SD), TKI-related adverse events (AEs), and pooled median progression-free survival (PFS) were calculated with 95% confidence intervals (CI). Complete response to TKIs was extremely rare (0.3%). The highest PR rate and longest PFS were observed for lenvatinib in differentiated thyroid cancer (69%, 95% CI: 57-81 and 19 months, 95% CI: 9-29, respectively) and vandetanib in medullary thyroid cancer (40%, 95% CI: 25-56 and 31 months, 95% CI: 19-43, respectively). Although the discontinuation rate due to AEs was similar for each TKI, there was a difference in the most frequently observed AE for each TKI (hand-foot syndrome for sorafenib, hypertension and proteinuria for lenvatinib, and QTc prolongation for vandetanib). The identified differences in the TKI efficacy and AE profiles may provide a better understanding of thyroid cancer treatment. Although TKIs are promising agents for thyroid cancer treatment, they are unlikely to lead to a cure. Thus, even in the TKI era, a multimodal treatment including surgery, radioiodine therapy, external beam radiotherapy, and TKIs is required to optimize patient chances of improved survival.
-
6.
Comparison of 5 Different PET Radiopharmaceuticals for the Detection of Recurrent Medullary Thyroid Carcinoma: A Network Meta-analysis.
Lee, SW, Shim, SR, Jeong, SY, Kim, SJ
Clinical nuclear medicine. 2020;(5):341-348
Abstract
PURPOSE The aim of this study is to investigate and compare the performance of different PET radiopharmaceuticals for the detection of recurrent medullary thyroid carcinoma (MTC) by performing a network meta-analysis (NMA) using direct comparison studies with 2 or more PET radiopharmaceuticals. METHODS PubMed and EMBASE were searched for the studies evaluating the performance of PET or PET/CT for the detection of recurrent MTC. The NMA was performed for different PET radiopharmaceuticals in both patient- and lesion-based analyses and with a threshold of serum calcitonin or carcinoembryonic antigen (CEA) levels and calcitonin doubling time. The consistency was evaluated by examining the agreement between direct and indirect treatment effects, and publication bias was assessed by funnel plot asymmetry tests. The surface under the cumulative ranking curve values were obtained to calculate the probability of each PET modality being the most effective diagnostic method. RESULTS A total of 306 patients from 14 direct comparison studies using 5 different PET radiopharmaceuticals (F-FDG, F-DOPA, Ga-somatostatin analogs, 3-O-methyl-6-[F]fluoro-DOPA, and C-methionine) for the detection of recurrent MTC was included. The detection rate of F-DOPA PET was significantly higher than that of FDG PET in both patient- and lesion-based analyses (patient-based analysis: odds ratio, 2.44; 95% confidence interval, 1.4-4.31; lesion-based analysis: odds ratio, 5.74; 95% confidence interval, 1.65-23.4). Among all PET radiopharmaceuticals, F-DOPA showed the highest surface under the cumulative ranking curve value in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time. CONCLUSIONS The results from this NMA indicate that F-DOPA PET clearly showed a best performance for the detection of recurrent MTC in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time.
-
7.
Evidence-Based Data About Prevalence and Risk of Malignancy of Thyroid Incidentalomas Detected by Different PET Radiopharmaceuticals.
Signore, G, Albano, D, Giovanella, L, Bertagna, F, Treglia, G
Current radiopharmaceuticals. 2020;(2):89-93
Abstract
BACKGROUND To date, several meta-analyses and systematic reviews have reported data about the prevalence and risk of malignancy of thyroid incidentalomas detected by different PET radiopharmaceuticals. OBJECTIVE This article aims to summarize the published evidence-based data about the prevalence and risk of malignancy of thyroid incidentalomas detected by different PET radiopharmaceuticals. METHODS A comprehensive computer literature search of systematic reviews and meta-analyses published up to July 2019 in PubMed/MEDLINE and Cochrane library databases regarding the prevalence and risk of malignancy of thyroid incidentalomas detected by different PET radiopharmaceuticals was carried out. RESULTS We have summarized the data about prevalence and risk of malignancy of thyroid incidentalomas detected by different PET radiopharmaceuticals (fluorine-18 fluorodeoxyglucose, radiolabelled choline and prostate-specific membrane antigen) taking into account 8 evidence-based articles. CONCLUSION Evidence-based data demonstrated that thyroid incidentalomas detected by different PET radiopharmaceuticals are not infrequent and their risk of malignancy is not negligible, in particular if focal pattern is evident at PET, thus requiring further clinical and instrumental evaluation.
-
8.
Vitamin D deficiency as a risk factor for thyroid cancer: A meta-analysis of case-control studies.
Zhao, J, Wang, H, Zhang, Z, Zhou, X, Yao, J, Zhang, R, Liao, L, Dong, J
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:5-11
Abstract
OBJECTIVE The association between vitamin D deficiency and thyroid cancer is controversial. Some studies have demonstrated that higher serum vitamin D levels might protect against thyroid cancer, whereas others have not, or have even indicated the opposite to be the case. The aim of this meta-analysis was to investigate the association between vitamin D deficicency and thyroid cancer and propose that vitamin D deficiency is a risk factor for thyroid cancer. METHODS This was a meta-analysis of 14 articles of the association between vitamin D deficiency and thyroid cancer. Databases including PubMed, Cochrane library, Sinomed, CNKI, Wanfang, and clinical trial register centers, were searched for case-control studies of vitamin D in thyroid cancer. RESULTS Fourteen studies were included in this meta-analysis. A fixed-effect model was used to merge the standardized mean difference value of serum 25-hydroxyvitamin D levels. The pooled effect showed that the levels of serum 25-hydroxyvitamin D were lower in patients with thyroid cancer preoperatively than in the controls (-0.22; 95% confidence interval [CI], -0.36 to -0.09; P = 0.001). There was no difference after thyroid cancer patients underwent thyroidectomy (-0.19; 95% CI, -0.47 to 0.10; P = 0.21). A fixed-effect model was used to pool the odds ratio of thyroid cancer and vitamin D deficiency. It showed that the pooled odds ratio from six studies was 1.30 (95% CI, 1.00-1.69; P = 0.05). Subgroup analysis of 25-hydroxyvitamin D levels between different pathologic characteristics in patients with thyroid cancer was summarized, but no statistical differences were determined. CONCLUSIONS Lower serum 25-hydroxyvitamin D levels were associated with increased risk for thyroid cancer. On the other hand, vitamin D deficiency may act as a risk factor for thyroid cancer.
-
9.
Urinary iodine is increased in papillary thyroid carcinoma but is not altered by regional population iodine intake status: a meta-analysis and implications.
Yan, AR, Zhang, X, Shen, H, Zhou, X, Li, R, Yuan, Z
Endocrine journal. 2019;(6):497-514
-
-
Free full text
-
Abstract
Excessive iodine intake has been associated with increased risk of thyroid cancer (TC) in many studies, but the results have not been consistent. Since it was common knowledge that urinary iodine (UI) is considered a sensitive marker of current iodine intake, we conducted a meta-analysis to clarify the association between high UI and TC. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the Cochrane Collaboration. Between-group meta-analyses were performed to compare UI between TC patients and the healthy/euthyroid subjects in local residents and benign thyroid nodules (BTN) patients. Then, between-group meta-analyses to compare the incidence rate of iodine excess were also conducted. The 22 case-control studies included in the meta-analyses represented 15,476 participants. It is the first time to clarify that UI was increased in PTC patients, but was not altered by regional population iodine intake status. Compared with BTN patients, PTC patients exhibited both higher UIC and higher odds ratio of iodine excess only in adequate iodine intake status subgroup; UIC, not the odds ratio of iodine excess, was higher in patients with PTC than those with BTN in above requirements iodine intake subgroup. A novel insight is offered that high UI in PTC patients was less influenced by regional population iodine intake status. It is indicted that high iodine intake is not a risk factor for PTC and high urinary iodine is just a specific characteristic of the disease.
-
10.
A Systematic Review and Meta-Analysis of Subsequent Malignant Neoplasm Risk After Radioactive Iodine Treatment of Thyroid Cancer.
Yu, CY, Saeed, O, Goldberg, AS, Farooq, S, Fazelzad, R, Goldstein, DP, Tsang, RW, Brierley, JD, Ezzat, S, Thabane, L, et al
Thyroid : official journal of the American Thyroid Association. 2018;(12):1662-1673
Abstract
Background: The potential risk of subsequent malignant neoplasms (SMNs) after radioactive iodine (RAI) treatment of thyroid cancer (TC) is an important concern. Methods: A systematic review was updated comparing the risk of SMNs in TC patients treated with RAI to TC patients without RAI. Six electronic databases were searched (up to March, 2018), supplemented with a hand search. Two reviewers independently screened citations, reviewed full-text papers, and critically appraised/abstracted data. Random-effects meta-analyses were conducted using crude data and data statistically adjusted for confounders. The outcomes were any SMN and specific SMNs for which sufficient data were available. Results: In total, 3506 unique electronic search citations and 93 full-text papers were examined, including 17 studies (3 systematic reviews and 14 original studies). Published knowledge syntheses were limited by inclusion of small numbers of studies, with two systematic reviews suggesting an increased risk of any SMN and one meta-analysis suggesting a reduced risk of breast SMN after RAI treatment. In a meta-analysis of crude data, the risk ratio of any SMN in RAI-treated TC patients was 0.98 ([confidence interval (CI) 0.76-1.27]; n = 10 studies of 65,539 individuals, heterogeneity Q = 64.26, degrees of freedom [df] = 9, p < 0.001, I2 = 85.99). The pooled risk ratio for any SMN, adjusted for confounders, was 1.16 ([CI 0.97-1.39]; n = 6 studies, data from at least 11,241 TC patients, Q = 10.86, df = 5, p = 0.054, I2 = 53.96). In secondary analyses examining specific SMNs, although relatively rare, the risk of subsequent leukemia was increased, but the risk of multiple myeloma was reduced in RAI-treated TC patients. There was no significant increased relative risk of breast cancer, salivary cancer, or combined hematologic malignancies according to RAI treatment status. Conclusions: The body of evidence on whether 131I treatment of thyroid cancer is associated with the primary outcome of any SMN is highly heterogeneous and complex. More research examining the long-term risk of specific SMNs after 131I treatment is needed.