New evidence on tumor suppressor activity of PTEN and KLLN in papillary thyroid carcinoma

Abstract

This study aimed to address the hypothesis that the expression of PTEN and KLLN tumor suppressor genes could diminish in papillary thyroid cancer (PTC) compared to paired normal tissue (PNT) and multinodular goiter (MNG). PTEN and KLLN expressions were assessed at both mRNA and protein levels in 82 tissue samples, including 30 PTC, 30 PNT, and 26 MNG using SYBR-Green Real-Time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Bioinformatics studies were performed to evaluate the genomic location and the genes promoter region. The mRNA expression of PTEN and KLLN in PTC was significantly lower than PNT (PTEN, P = 0.0033; KLLN, P = 0.0005). A significant decrease in the mRNA level of KLLN was also observed in PTC than MNG (P = 0.0304). Decreased level of PTEN mRNA (odds ratio=0.391; P = 0.013) or KLLN mRNA (odds ratio=0.023; P = 0.025) was associated with an increased risk of PTC tumorigenesis. Areas under the ROC curve for PTEN and KLLN were 0.69 and 0.78, respectively. PTEN and KLLN protein expressions in PTC compared to PNT or MNG were not significantly different. The bioinformatics studies revealed the sequence near the promoter region is lowly conserved across species. Four GC boxes were found upstream of the PTEN transcription start site (TSS), and one TATA box and one GC box were found upstream of KLLN TSS. The results suggest PTEN and KLLN are the two tumor suppressor genes that decreasing or loss of both of them occurs in sporadic PTC tumorigenesis. It appears they could have a promising application in both diagnostic and therapeutic areas.

Keywords: Gene expression; KLLN; Multinodular goiter; PTEN; Papillary thyroid carcinoma.