Reduction of PKHD۱L۱ gene expression in thyroid cancer and its relationship with tumor invasion

Thyroid cancer (TC) is a common endocrine malignancy that affects millions of people worldwide, with an increasing incidence rate over the past few decades. Despite advances in diagnostic and treatment modalities, the prognosis of TC remains poor, particularly for patients with advanced disease. The identification of novel biomarkers that can aid in early detection and treatment of TC is thus crucial. The polycystic kidney and liver disease gene ۱ (PKHD۱L۱) has been implicated in various cancers, including breast, lung, and colon cancer. However, its role in the development and progression of TC remains unclear. To investigate the expression of PKHD۱L۱ in TC tissue and its association with patient characteristics, tumor characteristics, and clinical outcomes, we conducted a comprehensive study. We extracted microarray and RNAseq data from the National Center for Biotechnology Information's Gene Expression Omnibus (NCBI-GEO) database using the Limma statistical algorithm to identify genes with differential expression between tumor tissue and healthy tissue adjacent to the tumor. We also collected tumor tissue and healthy tissue adjacent to the tumor from ۲۰ patients with TC at Sina Hospital, Isfahan. RNA extraction, cDNA production, and real-time polymerase chain reaction (PCR) were performed using exon crossing primers and cybergreen detection to quantify PKHD۱L۱ gene expression. Our results showed that PKHD۱L۱ gene expression was significantly decreased in TC tissue compared to healthy tissue adjacent to the tumor. This decrease was observed across all patient age groups and tumor subtypes. Furthermore, we found an inverse relationship between PKHD۱L۱ gene expression and patient age, as well as degree of tumor malignancy. Notably, patients with advanced disease had lower PKHD۱L۱ gene expression compared to those with early-stage disease. We also investigated the relationship between PKHD۱L۱ gene expression and promoter methylation levels in patients. Our results showed an increase in PKHD۱L۱ gene promoter methylation in patients compared to healthy individuals. This suggests that epigenetic silencing of the PKHD۱L۱ gene may contribute to its decreased expression in TC tissue. Our findings suggest that decreased PKHD۱L۱ gene expression may be a marker of TC tumor invasion, as it was more pronounced in tumors with extensive metastasis compared to those with limited metastasis. Further studies are needed to validate these findings and explore the underlying mechanisms by which PKHD۱L۱ regulates TC development and progression.

کلیدواژه ها:

thyroid cancer ، PKHD۱L۱ ، Real Time PCR