Combined quantitation of HMGA2 mRNA, microRNAs, and mitochondrial-DNA content enables the identification and typing of thyroid tumors in fine-needle aspiration smears

Autor: Mikhail K. Ivanov, Yulia A Veryaskina, Gevork A. Katanyan, Anastasia Malek, Igor F. Zhimulev, P. S. Demenkov, Eugenia S. Kozorezova, Sergei E. Titov
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
Pathology
Goiter
Translocation
Genetic
0302 clinical medicine
Thyroid cancer
medicine.diagnostic_test
microRNA
Thyroid
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Data Accuracy
preoperative diagnosis
medicine.anatomical_structure
Fine-needle aspiration
Oncology
Medullary carcinoma
030220 oncology & carcinogenesis
Preoperative Period
Female
Algorithms
Research Article
Thyroid nodules
Adult
medicine.medical_specialty
HMGA2
Adenoma
molecular markers
Biopsy
Fine-Needle
Real-Time Polymerase Chain Reaction
lcsh:RC254-282
DNA
Mitochondrial
Decision Support Techniques
Thyroid carcinoma
Diagnosis
Differential
03 medical and health sciences
Genetics
medicine
Biomarkers
Tumor
Humans
RNA
Messenger
Thyroid Neoplasms
Aged
business.industry
HMGA2 Protein
medicine.disease
MicroRNAs
030104 developmental biology
Feasibility Studies
business
Zdroj: BMC Cancer
BMC Cancer, Vol 19, Iss 1, Pp 1-14 (2019)
ISSN: 1471-2407
Popis: Background Analysis of molecular markers in addition to cytological analysis of fine-needle aspiration (FNA) samples is a promising way to improve the preoperative diagnosis of thyroid nodules. Nonetheless, in clinical practice, applications of existing diagnostic solutions based on the detection of somatic mutations or analysis of gene expression are limited by their high cost and difficulties with clinical interpretation. The aim of our work was to develop an algorithm for the differential diagnosis of thyroid nodules on the basis of a small set of molecular markers analyzed by real-time PCR. Methods A total of 494 preoperative FNA samples of thyroid goiters and tumors from 232 patients with known histological reports were analyzed: goiter, 105 samples (50 patients); follicular adenoma, 101 (48); follicular carcinoma, 43 (28); Hürthle cell carcinoma, 25 (11); papillary carcinoma, 121 (56); follicular variant of papillary carcinoma, 80 (32); and medullary carcinoma, 19 (12). Total nucleic acids extracted from dried FNA smears were analyzed for five somatic point mutations and two translocations typical of thyroid tumors as well as for relative concentrations of HMGA2 mRNA and 13 microRNAs and the ratio of mitochondrial to nuclear DNA by real-time PCR. A decision tree–based algorithm was built to discriminate benign and malignant tumors and to type the thyroid cancer. Leave-p-out cross-validation with five partitions was performed to estimate prediction quality. A comparison of two independent samples by quantitative traits was carried out via the Mann–Whitney U test. Results A minimum set of markers was selected (levels of HMGA2 mRNA and miR-375, − 221, and -146b in combination with the mitochondrial-to-nuclear DNA ratio) and yielded highly accurate discrimination (sensitivity = 0.97; positive predictive value = 0.98) between goiters with benign tumors and malignant tumors and accurate typing of papillary, medullary, and Hürthle cell carcinomas. The results support an alternative classification of follicular tumors, which differs from the histological one. Conclusions The study shows the feasibility of the preoperative differential diagnosis of thyroid nodules using a panel of several molecular markers by a simple PCR-based method. Combining markers of different types increases the accuracy of classification.
Databáze: OpenAIRE
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