Objective: An increasing number of studies have shown the potential diagnostic value of cell-free DNA (cfDNA) as a new biomarker in the management of thyroid cancer (TC); however, the accuracy of research results is inconsistent. This meta-analysis is the first to synthesize published results and evaluate the application value of circulating cfDNA in the diagnosis of TC.Methods: A search strategy was developed according to PICO (P: Patient; I: Intervention; C: Comparison; O: Outcome) principles. We searched 5 databases until October 2022. Original studies that examined cfDNA for the diagnosis of TC and used pathology as the gold standard were included in this meta-analysis. A random-effects model was used to pool the data extracted from individual studies, including the number of patients and the numbers of true positives, false positives, true negatives, and false negatives.Results: A total of 622 patients with TC, 547 patients with benign thyroid nodules, and 98 healthy individuals were included in 20 studies reported in 14 articles. The types of cfDNA included in the research include specific mutations of cfDNA, methylation of cfDNA, the content of cfDNA, and cfDNA index. After rigorous statistical analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.76 (95% confidence interval [CI] 0.62-0.85), 0.87 (95% CI 0.78-0.93), 5.08 (95% CI 3.3-10.3), 0.28 (95% CI 0.17-0.46), 21 (95% CI 9-49), and 0.89 (95% CI 0.86-0.91), respectively. The meta-regression results showed that the number of cfDNAs, cfDNA methylation status, and sample size were the sources of heterogeneity in the specificity of the study. A subgroup analysis showed that the quantitative analysis group (cfDNA level) had a higher diagnostic accuracy than that of the qualitative analysis group (cfDNA methylation, mutation, or integrity index), with a sensitivity of 0.84, specificity of 0.89, and area under the curve of 0.91. Conclusions:The results of this meta-analysis suggest that cfDNA has value as an adjunct for the diagnosis of TC. Quantitative detection of cfDNA can achieve relatively high diagnostic accuracy. However, due to heterogeneity, the test results based on cfDNA for TC should be interpreted with caution.Abbreviations: AUC = area under the curve, BTN = benign thyroid nodule, cfDNA = cell-free DNA, CI = confidence interval, CNKI = China National Knowledge Infrastructure, ctDNA = circulating tumor DNA, DOR = diagnostic odds ratio, HCC = hepatocellular carcinoma, NLR = negative likelihood ratio, PLR = positive likelihood ratio, qPCR = quantitative real-time polymerase chain reaction, SROC = summary receiver operating characteristic, TC = thyroid cancer, Tg = thyroglobulin.

ATP-binding cassette (ABC) transporters are a large superfamily of membrane proteins that facilitate the translocation of heterogeneous substrates. Studies indicate that ABC transporters may play important roles in various carcinomas. However, the correlation between ABC transporters and immunomodulation in thyroid carcinoma (TC), as well as the prognoses for this disease, is poorly understood.TC data from The Cancer Genome Atlas (TCGA) database were used to identify prognostic hallmark ABC transporters associated with immune cell infiltration patterns via multiple bioinformatic analyses. Thereafter, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression of these selected hallmark ABC transporters in both TC and para-cancerous thyroid tissues. Of a total of 49 ABC transporters, five (ABCA8, ABCA12, ABCB6, ABCB8, and ABCC10) were identified as hallmark ABC transporters. All five were differentially expressed in TC and associated with the relapse-free survival rates of patients with TC. Immunoregulation by these five hallmark ABC transporters involved the modulation of various aspects of immune cell infiltration, such as hot or cold tumor subsets and the abundances of infiltrating immune cells, as well as specific immunomodulators and chemokines. Besides the diverse significantly correlated factors, the five hallmark ABC transporters and correlated genes were most highly enriched in plasma membrane, transporter activity, and transmembrane transport of small molecules. In addition, many chemicals, namely bisphenol A and vincristine, affected the expression of these five transporters. The qRT-PCR results of collected TC and para-cancerous thyroid tissues were consistent with those of TCGA. The findings in this study may reveal the role played by these five hallmark ABC transporters in regulating immune cell infiltration patterns in TC as well as the molecular mechanisms underlying their functions, leading to a better understanding of their potential prognostic and immunotherapeutic values.