Key molecules associated with thyroid carcinoma prognosis: A study based on transcriptome sequencing and GEO datasets

Abstract

Background: Thyroid carcinoma (THCA) has a low mortality rate, but its incidence has been rising over the years. We need to pay attention to its progression and prognosis. In this study, a transcriptome sequencing analysis and bioinformatics methods were used to screen key genes associated with THCA development and analyse their clinical significance and diagnostic value.

Methods: We collected 10 pairs of THCA tissues and noncancerous tissues, these samples were used for transcriptome sequencing to identify disordered genes. The gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Comprehensive analysis of thyroid clinicopathological data using The Cancer Genome Atlas (TCGA). R software was used to carry out background correction, normalization and log2 conversion. We used quantitative real-time PCR (qRT-PCR) and Western blot to determine differentially expressed genes (DEGs) expression in samples. We integrated the DEGs expression, clinical features and progression-free interval (PFI). The related functions and immune infiltration degree were established by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA). The UALCAN database was used to analyse the methylation level.

Results: We evaluated DEGs between normal tissue and cancer. Three genes were identified: regulator of G protein signaling 8 (RGS8), diacylglycerol kinase iota (DGKI) and oculocutaneous albinism II (OCA2). The mRNA and protein expression levels of RGS8, DGKI and OCA2 in normal tissues were higher than those in THCA tissues. Better survival outcomes were associated with higher expression of RGS8 (HR=0.38, P=0.001), DGKI (HR=0.52, P=0.022), and OCA2 (HR=0.41, P=0.003). The GO analysis, KEGG analysis and GSEA proved that the coexpressed genes of RGS8, DGKI and OCA2 were related to thyroid hormone production and peripheral downstream signal transduction effects. The expression levels of RGS8, DGKI and OCA2 were linked to the infiltration of immune cells such as DC cells. The DNA methylation level of OCA2 in cancer tissues was higher than that in the normal samples.

Conclusions: RGS8, DGKI and OCA2 might be promising prognostic molecular markers in patients with THCA and reveal the clinical significance of RGS8, DGKI and OCA2 in THCA.

Keywords: DGKI; DNA methylation; OCA2; RGS8; immune infiltration; prognosis; thyroid carcinoma; transcriptome sequencing.