Identification of Dihydrodiol Dehydrogenase (DHDH) gene as a potential biomarker for Thyroid Carcinoma by bioinformatics analysis
Identification of Dihydrodiol Dehydrogenase (DHDH) gene as a potential biomarker for Thyroid Carcinoma by bioinformatics analysis
Atousa Ghorbani,1,*Aida Ahmadpour,2
1. Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran 2. B.C student of Public health, Student Researches Committee, Gonabad university of Medical Sciences, Gonabad, Iran
Introduction: Thyroid carcinoma (THCA) is the most common endocrine malignancy, accounting for ~2.1% of all cancer diagnoses worldwide. It is mostly detected around the course of the thyroglossal duct or laterally in the neck, also in the subdiaphragmatic organs and distant places such as the mediastinum. Although most patients are asymptomatic, symptoms related to the size of the tumor and its relationship with surrounding tissues can also appear. It can occur at any age, as well as it is more common in young adults, the mortality rate is decreased due to early diagnosis, but it is different in racial groups. Dihydrodiol dehydrogenase (DHDH) encodes an enzyme that belongs to the family of dihydrodiol dehydrogenases, which exists in numerous forms in mammalian tissues and are involved in the metabolism of sugars and xenobiotics in the endocrine system. Given that the variability of incidence-based mortality in the different races has not been studied. The aim of this study is to investigate the DHDH gene in clinical parameters based on the Pathological stage in the four racial groups.
Methods: In this Descriptive-analytical study to identify genes involved in THCA development, we analyzed the Cancer Genome Atlas (TCGA) data. Besides, to facilitate our understanding of such genes that participated in tumor progression, we analyzed a database OncoDB to explore abnormal patterns in gene expression related to clinical data that were identified. Also, differentially expressed genes (DEGs) by the OncoDB online database were identified and then by the TMP method normalized. Finally, functional enrichment analysis was applied. Criteria for including patient data in the present study are demographic information such as race and pathological stage. The TCGA datasets related to THCA consisted of 50 normal, 505 Cancer samples, and 400 DEGs (|log FC| > 1; P < 0.05) in individuals with TCHA compared with the normal samples via using the available numerical mRNA expression values.
Results: The expression of the DHDH gene in TCHA increases about two times with LogFC =1, while it has a very low expression in normal tissue. The ONCODB data have been used to investigate the clinical effect of DHDH gene expression increase in the pathological stage. The expression profile of DHDH was included: Cancer sample average3.7; Cancer sample median: 2.8; Normal sample average: 0.5 Normal sample median: 1; log2 fold change: 1.49. Also, the results of demographic information based on pathological stage chart analysis show that the expression in the late stage is higher compared to patients in the early stage.
According to the average expression of the DHDH gene in 27 samples of African-American patients, 1 sample of AMERICAN Indians, 50 samples of Asians, and 324 samples of White patients are respectively 3.0, 4.5, 4.6, and 3.7. The higher average of expression of target gene compared to the median reported, which respectively as, 1.8, 4.5, 2.8, and 2.9and these values indicate increased expression in the samples.
This gene was significantly related to demographic parameters such as race and pathological stage. Conforming to the analysis of gene expression with ANOVA-Pvalue=1.5e-09 in different stages of the disease, it can be concluded that with the increase in DHDH gene expression, the tumor size increases, and the disease progresses towards metastasis.
Conclusion: According to the larger number of samples and the lower average in whites, it is concluded that the increase in expression in Asian and African-American patients is more than in white patients and the distribution of data in these patients is more scattered. The results of this study collectively revealed that altered DHDH gene expression levels might be responsible for racial differences in the carcinogenesis of THCA and target gene expression promotes the progression of related pathological stages of THCA. Therefore, the DHDH gene is expected to become a molecular target for THCA treatment.