Abstract
Papillary thyroid carcinoma (PTC), the most prevalent cancer of the thyroid, is more common in women than in men. To uncover the expression profile of FOXE1 gene in PTC tumor etiology. Microarray and RNA sequencing data on PTC in humans were analyzed. Eleven PTC tumor tissue samples and their neighboring normal tissue samples were collected. RT-qPCR was performed. Data normality, ROC construction, and logistic regression analysis were conducted. PTC tumors, normal tissues surrounding tumors, patients of different sexes and ages, metastasizing tumors, and tumor variants were assessed for FOXE1 expression. Eleven PTC tissues were obtained from seven women and four men. Among the PTC subtypes, there were two FV-PTCs, four C-PTCs, one microcarcinoma, and four tissues with an unknown subtype. FOXE1 gene expression was significantly increased in PTC tumors with dimensions less than 10 mm (relative expression = 14.437, p = 0.050). A significant increase in FOXE1 gene expression was observed in the normal tissue adjacent to the tumor, which was less than 10 mm in size, compared to the normal tissue adjacent to the tumor, which was larger than 10 mm (relative expression = 41.760, p = 0.0001). Females diagnosed with PTC showed a significant reduction in FOXE1 mRNA levels compared to their male counterparts (relative expression = 0.081, p = 0.042). In contrast to adjacent normal tissue, there was a significant reduction in FOXE1 gene expression in FV-PTC (relative expression = 0.044 and p = 0.0001). PTC tumors under 10mm had higher FOXE1 gene expression than larger tumors; normal tissue adjacent to smaller tumors also had higher FOXE1 expression. Females with PTC, regardless of their subtype, expressed less FOXE1 mRNA than males. FV-PTC tissues exhibited lower expression of FOXE1 mRNA than their adjacent normal tissues.
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The entirety of the information provided in the manuscript can be accessed via the following URLs: https://www.ncbi.nlm.nih.gov/geo/ and https://ualcan.path.uab.edu/analysis.html.
Abbreviations
- TNM:
-
Tumor-node-metastasis cancer staging system, includes T for tumor, N for lymph node spread, and M for metastasis. The number following N indicates the extent of lymphatic metastasis. For example, PTC-N0 represents tumor tissues without metastasis, while PTC-N1 represents those with metastasis
- PTC:
-
Papillary thyroid cancer, is prevalent and can develop at any age. It grows slowly, spreads to neck lymph nodes, and generally has a positive prognosis
- C-PTC:
-
Conventional or classical PTC, has papillary architecture with fibrovascular cores and psammoma bodies, and tumor cells with enlarged, overlapping nuclei, nuclear grooves, and irregularities in the nuclear membrane. It is the most common variants of PTC, accounting for 55% to 66% of cases
- FV-PTC:
-
Follicular variant-PTC, is a histological variant of PTC with follicular architecture. These tumors grossly resemble follicular carcinoma, with mean tumor size falling between C-PTC and follicular thyroid carcinoma. It is the second most common PTC subtype, accounts for 9% to 22.5% of cases
- Microcarcinoma:
-
A thyroid papillary microcarcinoma is a variant of PTC that is less than 10 millimeters in diameter
- ATC:
-
Anaplastic thyroid cancer, the most advanced and aggressive form, is uncommon, occurring in less than 2% of thyroid cancer patients, and primarily affecting individuals over 60 years old
- Microarray:
-
Is a technique used in the laboratory to assess the level of gene expression on a large scale
- RNAseq:
-
RNA sequencing, uses next-generation sequencing to assess the amount and presence of RNA in a sample, providing a snapshot of the RNA pool within the cells
- RT-qPCR:
-
Reverse transcription quantitative polymerase chain reaction, is a technique used to detect and quantify RNA by transcribing mRNA into complementary DNA or cDNA
- TCGA:
-
The cancer genome atlas, is a notable cancer genomics database which has over 20,000 primary cancer and matched normal samples from 33 different types of cancer
- LogFC:
-
Log2 fold change, is employed to interpret mRNA expression levels. A logFC of 1 indicates twice the expression
- Adj. p val:
-
Adjusted p value, is the minimum significance level at which a specific comparison will be deemed statistically significant during multiple comparison testing
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Acknowledgements
Volunteers are thanked for their time and effort by the author. Funding for this study was provided by the Departments of Research, Technology, and Graduate Offices of the University of Isfahan, Iran. A sincere thank you is extended to Dr. Mohsen Kolahdouzan, thoracic surgeon, for his kindness, patience and responsibility in the acquisition of thyroid tissues. It is also appropriate to express gratitude to Dr. Keivan Shirneshan for approving the pathological results.
Funding
This study was conducted at Isfahan University of Iran and was supported financially by the Departments of Research, Technology and Graduate Offices (Grant Number: A\98\5727).
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RH: Design, data analysis, interpretation, manuscript drafting, and final approval of the manuscript. S-MJ: Conceptualization, design, data analysis, interpretation, financial support, manuscript drafting, critical revision for critical intellectual contents, and final approval of the manuscript. MK, S-MJ: Conceptualization, design, interpretation, manuscript drafting, and final approval of the manuscript.
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All patients recommended for thyroid surgery at Al-Zahra and Sina hospitals in Isfahan had to sign a consent form. Isfahan University’s institutional review board (IR.UI.REC.1398.060) approved the acquisition of human tissues. All the experiments and procedures performed in this study specially but not limited to human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Authors sincerely thank the volunteers for their participation.
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Hajian, R., Javadirad, SM. & kolahdouzan, M. FOXE1 Gene is a Probable Tumor Suppressor Gene with Decreased Expression as Papillary Thyroid Cancers Grow, and is Absent in Anaplastic Thyroid Cancers. Biochem Genet (2024). https://doi.org/10.1007/s10528-023-10642-z
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DOI: https://doi.org/10.1007/s10528-023-10642-z