An investigation on the expression of miRNAs including miR-144 and miR-34a in plasma samples of RET-positive and RET-negative medullar thyroid carcinoma patients

J Cell Physiol. 2020 Feb;235(2):1366-1373. doi: 10.1002/jcp.29055. Epub 2019 Jul 11.

Abstract

Medullary thyroid carcinoma (MTC) is a scarce cancerous disease, originating from parafollicular C cells of the thyroid gland. MTC can be manifested as an aggressive carcinoma with metastasis, especially in sporadic forms. Mutations of the rearranged during transfection (RET) proto-oncogene occurs in all hereditary and a few somatic MTCs, so detection of RET mutations is needed for prompt and appropriate treatment. MicroRNAs (miRNAs) are noncoding regulatory RNAs. Extensive studies have done in progress or suppression of several types of cancers such as MTCs with the remarkable application as prognostic markers. Of the effective miRNAs in cancers, miR-144 and miR-34 were evaluated in our study. Blood samples of 25 RET-positive and 25 RET-negative blood samples of patients with MTC were evaluated for these miRNAs, using quantitative real-time polymerase chain reaction (RT-qPCR). Analysis of the results was performed by the 2 -ΔΔCt method, showing that miR-144 and miR-34a expression had a relative increase in patients with MTC compared with normal control samples and also in RET positives versus RET negatives. We recruited 50 out of 350 MTC plasma samples (27 female and 23 male) which were selected based on RET mutation in exon 11 (25 RET-positive and 25 RET-negative), with a mean ± SD age of 37.04 ± 1.74 years. Receiver operating characteristic (ROC) curve analysis was done to investigate the prognostic value of these miRNAs; although, they showed no significant prognostic value as MTC biomarkers in plasma samples. In conclusion, miRNAs can be used as biomarkers of cancers such as MTC; however, more studies are needed to find the best candidate miRNAs for the diagnosis of cancers.

Keywords: MTC; RET; ROC curve analysis; miR-144; miR-34a; real-time PCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Neuroendocrine / blood
  • Carcinoma, Neuroendocrine / genetics*
  • Female
  • Humans
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Mutation
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret / genetics
  • Thyroid Neoplasms / blood
  • Thyroid Neoplasms / genetics*

Substances

  • Biomarkers, Tumor
  • MAS1 protein, human
  • MIRN144 microRNA, human
  • MIRN34 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret
  • RET protein, human

Supplementary concepts

  • Thyroid cancer, medullary