ATR-FTIR spectroscopy and CDKN1C gene expression in the prediction of lymph nodes metastases in papillary thyroid carcinoma

Spectrochim Acta A Mol Biomol Spectrosc. 2020 Mar 5:228:117693. doi: 10.1016/j.saa.2019.117693. Epub 2019 Oct 24.

Abstract

Thyroid cancer has become in recent years the most common endocrine malignancy. Among its different types, papillary thyroid carcinoma (PTC) has the highest incidence. PTC is slow growing, but shows a high rate of lymph node metastasis. Tissue biochemical characterization and identification of molecular markers can facilitate stratification of patients into those requiring surgical assessment of lymph nodes and patients for whom this surgical procedure is unnecessary; thus, leading to a more accurate prognosis. To this end, the study aimed to predict lymph node metastasis by Attenuated Total Reflectance - Fourier transform infrared (ATR-FTIR) spectroscopy of primary PTC tumors. Another objective of the study was to determine whether CCNA1, CDKN1C, FOS, HSPA5, JUN, KSR1, MAP2K6, MAPK8IP2 and SFN gene expression in primary PTC tumors could be used as predictive markers of lymph node metastasis. Three PTC with lymph node involvement (PTC+), six PTC without lymph node involvement (PTC-), and five normal (N) thyroid tissues were used for FTIR spectroscopy analysis; while 18 PTC+, 17 PTC-, and 6 N samples were used for molecular analysis by real-time quantitative PCR (RT-qPCR). FTIR spectral analysis revealed changes in phosphate groups possibly associated with nucleic acid (1236 cm-1), and protein/lipids (1452, 2924, 3821 cm-1) in PTC + compared to PTC-, and multivariate analysis could distinguish the two groups. Molecular analysis showed significant increase in CDKN1C gene expression in PTC + compared to PTC-. Being a cell growth regulator, increased CDKN1C provides some supporting evidence to the FTIR spectroscopy based finding of increased nucleic acids in PTC+. Thus, the study suggests the possibility of using FTIR spectroscopy and CDKN1C expression for predicting metastasis using primary tumor alone.

Keywords: CDKN1C gene; FTIR; Gene expression; Lymph nodes metastases; Papillary thyroid cancer; Predictive molecular markers; Spectroscopy.

MeSH terms

  • Adult
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p57 / metabolism
  • Discriminant Analysis
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis / genetics*
  • Male
  • Middle Aged
  • Principal Component Analysis
  • Spectroscopy, Fourier Transform Infrared
  • Thyroid Cancer, Papillary / genetics*

Substances

  • CDKN1C protein, human
  • Cyclin-Dependent Kinase Inhibitor p57
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human