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MicroRNA-Based Risk Score for Predicting Tumor Progression Following Radioactive Iodine Ablation in Well-Differentiated Thyroid Cancer Patients: A Propensity-Score Matched Analysis.

ABSTRACT: To identify molecular markers that can accurately predict aggressive tumor behavior at the time of surgery, a propensity-matching score analysis of archived specimens yielded two similar datasets of DTC patients (with and without RAI). Bioinformatically selected microRNAs were quantified by qRT-PCR. The risk score was generated using Cox regression and assessed using ROC, C-statistic, and Brier-score. A predictive Bayesian nomogram was established. External validation was performed, and causal network analysis was generated. Within the eight-year follow-up period, progression was reported in 51.5% of cases; of these, 48.6% had the T1a/b stage. Analysis showed upregulation of miR-221-3p and miR-222-3p and downregulation of miR-204-5p in 68 paired cancer tissues (p < 0.001). These three miRNAs were not differentially expressed in RAI and non-RAI groups. The ATA risk score showed poor discriminative ability (AUC = 0.518, p = 0.80). In contrast, the microRNA-based risk score showed high accuracy in predicting tumor progression in the whole cohorts (median = 1.87 vs. 0.39, AUC = 0.944) and RAI group (2.23 vs. 0.37, AUC = 0.979) at the cutoff >0.86 (92.6% accuracy, 88.6% sensitivity, 97% specificity) in the whole cohorts (C-statistics = 0.943/Brier = 0.083) and RAI subgroup (C-statistic = 0.978/Brier = 0.049). The high-score group had a three-fold increased progression risk (hazard ratio = 2.71, 95%CI = 1.86-3.96, p < 0.001) and shorter survival times (17.3 vs. 70.79 months, p < 0.001). Our prognostic microRNA signature and nomogram showed excellent predictive accuracy for progression-free survival in DTC.

SUBMITTER: Toraih EA

PROVIDER: S-EPMC8468667 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ContextAlthough response to therapy assessment is a validated tool for dynamic risk stratification in patients with differentiated thyroid cancer (DTC) treated with total thyroidectomy (TT) and radioactive iodine therapy (RAI), it has not been well studied in patients treated with lobectomy or TT without RAI. Because these responses to therapy definitions are heavily dependent on serum thyroglobulin (Tg) levels, modifications of the original definitions were needed to appropriately classify patients treated without RAI.ObjectiveThis study aimed to validate the response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI.Design and settingThis was a retrospective study, which took place at a referral center.PatientsA total of 507 adults with DTC were treated with lobectomy (n = 187) or TT (n = 320) without RAI. They had a median age of 43.7 y, 88% were female, 85.4% had low risk, and 14.6% intermediate risk.Main outcome measureMain outcome measured was recurrent/persistent structural evidence of disease (SED) during a median followup period of 100.5 months (24-510).ResultsRecurrent/persistent SED was observed in 0% of the patients with excellent response to therapy (nonstimulated Tg for TT < 0.2 ng/mL and for lobectomy < 30 ng/mL, undetectable Tg antibodies [TgAb] and negative imaging; n = 326); 1.3% with indeterminate response (nonstimulated Tg for TT 0.2-5 ng/mL, stable or declining TgAb and/or nonspecific imaging findings; n = 2/152); 31.6% of the patients with biochemical incomplete response (nonstimulated Tg for TT > 5 ng/mL and for lobectomy > 30 ng/mL and/or increasing Tg with similar TSH levels and/or increasing TgAb and negative imaging; n = 6/19) and all (100%) patients with structural incomplete response (n = 10/10) (P < .0001). Initial American Thyroid Association risk estimates were significantly modified based on response to therapy assessment.ConclusionsOur data validate the newly proposed response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI as an effective tool to modify initial risk estimates of recurrent/persistent SED and better tailor followup and future therapeutic approaches. This study provides further evidence to support a selective use of RAI in DTC.

Dataset Information

MicroRNA-Based Risk Score for Predicting Tumor Progression Following Radioactive Iodine Ablation in Well-Differentiated Thyroid Cancer Patients: A Propensity-Score Matched Analysis.

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