CCNA1 gene as a potential diagnostic marker in papillary thyroid cancer.

The malignancy that most affects the endocrine system is thyroid neoplasm, with an increasing incidence over the years. The most prevalent histological type of the carcinomas that affect the thyroid gland is papillary carcinoma with a prevalence of 80 % worldwide. The current diagnostic methodology may present inconclusive results, emphasizing the need for new effective and sensitive techniques to aid the diagnosis. For this, it is necessary to understand molecular and protein mechanisms in the identification of diagnostic and predictive markers in the lesions. The Cyclin A1 protein, encoded by the CCNA1 gene, is an important cell cycle regulator, belonging to the MAPK/ERK signaling pathway directly involved with thyroid cancer. The aim of this study was to evaluate the CCNA1 gene and Cyclin A1 protein expression in papillary thyroid carcinoma, follicular thyroid carcinoma, and benign thyroid lesions, by real time quantitative PCR and immunohistochemistry analysis, respectively, to verify their roles as potential diagnostic and predictive markers to future applications in the clinical routine. Overexpression of CCNA1 gene was observed in the papillary carcinoma group compared to the normal group (P = 0.0023), benign lesions (P = 0.0011), colloid goiter (P = 0.0124), and follicular carcinoma (P = 0.0063). No differential expression was observed in the papillary primary tumor group from negative lymph nodes compared with the one from positive lymph nodes (P = 0.3818). Although an increased expression of Cyclin A1 was observed in the PTC group compared to the other one in the IHC analysis, no significant difference was observed (Fisher's exact Test). A Cyclin A1 overexpression was detected with weak to mid-moderate immunoreactivity in the benign group (k = 0.56), (score 1.5); mid-moderate to moderate in the goiter group (k = 0.58); weak in the FTC group (k = 0.33); and mid-moderate to moderate in the PTC group (k = 0.48). Due to the small sample size in the IHC analysis and to the fact that not all RNA is translated into protein, the diagnostic potential of Cyclin A1 could not be assessed. However, these findings highlight the potential of the CCNA1 gene as a diagnostic marker for papillary thyroid carcinoma.

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

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.