Gene Expression Patterns Unveil New Insights in Papillary Thyroid Cancer

Saftencu, Mihai; Braicu, Cornelia; Cojocneanu, Roxana; Buse, Mihail; Irimie, Alexandru; Piciu, Doina; Berindan‐Neagoe, Ioana

doi:10.3390/medicina55080500

Cited by 12 publications

(11 citation statements)

References 28 publications

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“…Thyroseq v3 indicates a PLR of 2.8 (95% CI: 1.2-6.3) and NLR of 0.02 [0.00-2.69], as displayed in Table 2. Additionally, we revealed a high DOR with a large 95% CI [157 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)723)]. The area under the SROC curve was 0.95 (95% CI: 0.93-0.97; Supplementary Figure 1).…”

Section: Diagnostic Performance Of Thyroseq V3mentioning

confidence: 94%

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Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

et al. 2021

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BackgroundMolecular tests are being used increasingly as an auxiliary diagnostic tool so as to avoid a diagnostic surgery approach for cytologically indeterminate thyroid nodules (ITNs). Previous test versions, Thyroseq v2 and Afirma Gene Expression Classifier (GEC), have proven shortcomings in malignancy detection performance.ObjectiveThis study aimed to evaluate the diagnostic performance of the established Thyroseq v3, Afirma Gene Sequencing Classifier (GSC), and microRNA-based assays versus prior iterations in ITNs, in light of “rule-in” and “rule-out” concepts. It further analyzed the impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) reclassification and Bethesda cytological subtypes on the performance of molecular tests.MethodsPubmed, Scopus, and Web of Science were the databases used for the present research, a process that lasted until September 2020. A random-effects bivariate model was used to estimate the summary sensitivity, specificity, positive (PLR) and negative likelihood ratios (NLR), and area under the curve (AUC) for each panel. The conducted sensitivity analyses addressed different Bethesda categories and NIFTP thresholds.ResultsA total of 40 eligible studies were included with 7,831 ITNs from 7,565 patients. Thyroseq v3 showed the best overall performance (AUC 0.95; 95% confidence interval: 0.93–0.97), followed by Afirma GSC (AUC 0.90; 0.87–0.92) and Thyroseq v2 (AUC 0.88; 0.85–0.90). In terms of “rule-out” abilities Thyroseq v3 (NLR 0.02; 95%CI: 0.0–2.69) surpassed Afirma GEC (NLR 0.18; 95%CI: 0.10–0.33). Thyroseq v2 (PLR 3.5; 95%CI: 2.2–5.5) and Thyroseq v3 (PLR 2.8; 95%CI: 1.2–6.3) achieved superior “rule-in” properties compared to Afirma GSC (PLR 1.9; 95%CI: 1.3–2.8). Evidence for Thyroseq v3 seems to have higher quality, notwithstanding the paucity of studies. Both Afirma GEC and Thyroseq v2 performance have been affected by NIFTP reclassification. ThyGenNEXT/ThyraMIR and RosettaGX show prominent preliminary results.ConclusionThe newly emerged tests, Thyroseq v3 and Afirma GSC, designed for a “rule-in” purpose, have been proved to outperform in abilities to rule out malignancy, thus surpassing previous tests no longer available, Thyroseq 2 and Afirma GEC. However, Thyroseq v2 still ranks as the best rule-in molecular test.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier CRD42020212531.

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Section: Diagnostic Performance Of Thyroseq V3mentioning

confidence: 94%

“…Approximately three-quarters of these were benign on surgical pathology, indicating unnecessary surgical removal ( 6 ). Advances in the genetics of thyroid tumorigenesis have led to the development of a series of molecular tests to complement cytology and improve the risk-based stratification of ITNs ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

et al. 2021

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“…When Saftencu et.al. observed papillary thyroid cancer RNA, ITGA10, and other biological adhesion genes suggested a prognostic impact in linking gene expression to patient survival [30]. We hypothesize that the up regulation of adhesion genes could play an important role in tumorigenesis by impacting tumor cell aggregation and metastasis.…”

Section: Upregulated Gene Processes Induce Apoptosis and Inhibit Metamentioning

confidence: 85%

An Assessment of InP/ZnS as Potential Anti-Cancer Therapy: Quantum Dot Treatment Increases Apoptosis in HeLa Cells

Davenport

Horstmann

Patel

et al. 2021

JNT

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InP/ZnS quantum dots (QDs) are an emerging option in QD technologies for uses of fluorescent imaging as well as targeted drug and anticancer therapies based on their customizable properties. In this study we explored effects of InP/ZnS when treated with HeLa cervical cancer cells. We employed XTT viability assays, reactive oxygen species (ROS) analysis, and apoptosis analysis to better understand cytotoxicity extents at different concentrations of InP/ZnS. In addition, we compared the transcriptome profile from the QD-treated HeLa cells with that of untreated HeLa cells to identify changes to the transcriptome in response to the QD. RT-qPCR assay was performed to confirm the findings of transcriptome analysis, and the QD mode of action was illustrated. Our study determined both IC50 concentration of 69 µg/mL and MIC concentration of 167 µg/mL of InP/ZnS. It was observed via XTT assay that cell viability was decreased significantly at the MIC. Production of superoxide, measured by ROS assay with flow cytometry, was decreased, whereas levels of nitrogen radicals increased. Using analysis of apoptosis, we found that induced cell death in the QD-treated samples was shown to be significantly increased when compared to untreated cells. We conclude InP/ZnS QD to decrease cell viability by inducing stress via ROS levels, apoptosis induction, and alteration of transcriptome.

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“…In particular, activating mutations of BRAFV600E [15], RAS, and TERT promoter genes [16], and rearrangements of RET/PTC [17] and PAX8/PPARγ genes [18] are known to be associated explicitly with TC initiation and progression [19]. However, not all aggressive tumors exhibit these genetic variations [20], and several genes exhibit an altered expression that cannot be attributed to mutations, rearrangements, or amplification, but they rather are epigenetically dysregulated [21], as evidenced recently by bioinformatic analysis that evaluated the global gene expression pattern in thyroid cancer subtypes and identified their differentially expressed genes [22]. They can serve as markers of prognostic significance.…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Value of MicroRNAs in Thyroid Cancers—A Systematic Review and Meta-Analysis

Silaghi

Lozovanu

Silaghi

et al. 2020

Cancers

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Thyroid cancer (TC) includes various phenotypes, from indolent to highly aggressive cancer. The limitations of the current prognostication systems to predict the recurrence risk and the variability in expression of the genes involved in the thyroid carcinogenesis uncover the need for new prognostic biomarkers by taking into account potential epigenetic differences. We aimed to summarize the current knowledge regarding the prognostic impact of microRNAs (miRNAs) in TC. A literature search was conducted in PubMed, Embase, Scopus, and Web of Science databases. Both upregulated and downregulated miRNAs are significantly correlated with worse overall survival (hazard ratio (HR) = 5.94, 95% CI: 2.73–12.90, p < 0.001; HR = 0.51, 95% CI: 0.26–0.96, p = 0.048) disease/recurrence-free survival (HR = 1.58, 95% CI: 1.08–2.32, p = 0.003; HR = 0.37, 95%, CI: 0.24–0.60, p < 0.001). Sensitivity analysis revealed a significant association between the higher expression of miR-146b, miR-221, and miR-222 and the recurrence of papillary TC (OR = 9.11, 95% CI 3.00 to 27.52; p < 0.001; OR = 3.88, 95% CI 1.34 to 11.19, p < 0.001; OR = 6.56, 95% CI 2.75 to 15.64, p < 0.001). This research identified that miR-146b, miR-221, and miR-222 could serve as potential prognostic biomarkers in TC, particularly in PTC. Further studies are needed to strengthen these findings and sustain its clinical applicability.

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Gene Expression Patterns Unveil New Insights in Papillary Thyroid Cancer

Cited by 12 publications

References 28 publications

Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

An Assessment of InP/ZnS as Potential Anti-Cancer Therapy: Quantum Dot Treatment Increases Apoptosis in HeLa Cells

The Prognostic Value of MicroRNAs in Thyroid Cancers—A Systematic Review and Meta-Analysis

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