Expression and molecular profiles of the AlkB family in ovarian serous carcinoma

Abstract

AlkB family of Fe (II) and α-ketoglutarate-dependent dioxygenases plays essential roles in development of ovarian serous carcinoma (OV). However, the molecular profiles of AlkB family in OV have not been clarified. The results indicated that the expression of ALKBH1/3/5/8 and FTO was lower in OV patients while ALKBH2/4/6/7 expression was higher. There was a strong correlation between ALKBH5/7 and pathological stage of OV patients. Kaplan-Meier plotter revealed that OV patients with high ALKBH4 level showed longer overall survival (OS). However, patients with high levels of ALKBH5/6 and FTO showed shorter OS and progression-free survival (PFS). Genetic alterations using cBioPortal revealed that the alteration rates of FTO were the highest. We also found that the functions of AlkB family were linked to several cancer-associated signaling pathways, including chemokine receptor signaling. TIMER database indicated that the AlkB family had a strong relationship with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Next, DiseaseMeth databases revealed that the global methylation levels of ALKBH1/2/3/4/5/6/7/8 and FTO were all lower in OV patients. Thus, our findings will enhance the understanding of AlkB family in OV pathology, and provide novel insights into AlkB-targeted therapy for OV patients.

Keywords: AlkB family; expression profiles; infiltrating immune cells; methylation; ovarian serous carcinoma.

Figure 1

Differential mRNA expression analysis of the AlkB family in OV and normal tissues. The expression profiles were collected from the GEPIA databases.

Figure 2

The relative expression levels of the AlkB family in OV patients. GEPIA databases were used to evaluate the relative expression levels of the AlkB family in OV patients.

Figure 3

The relationship between the expression of the AlkB family and the pathological stage of OV patients (GEPIA). GEPIA databases were used to evaluate the correlations of the AlkB family with the pathological stage of OV patients.

Figure 4

The correlations of AlkB family expression with patients’ OS. These OS survival curves were collected from Kaplan-Meier plotter.

Figure 5

The correlations of AlkB family expression with PFS in OV patients. Kaplan-Meier plotter was used to assess the correlation of AlkB family members with the patients’ PFS time.

Figure 6

Genetic alterations and interaction analyses of the AlkB family in OV patients. (A) Genetic alteration of the AlkB family in OV patients analyzed with cBioPortal. (B) The interaction analysis of the AlkB family was evaluated by STRING. (C) Analysis of the interaction between the AlkB family and chemokine signaling-associated biomarkers. (D) The 150 most frequently altered genes identified from cBioPortal that are linked to the AlkB family in OV patients.

Figure 7

The biological pathways of the AlkB family were evaluated by the WebGestalt database. (A) Bar plot of GO enrichment in cellular components, biological processes, and molecular functions. (B) The bar plot of KEGG enrichment.

Figure 8

The relationship between immune cell infiltration and the expression of the AlkB family. The Timer database was used to analyze the effect of (A) ALKBH1, (B) ALKBH2, (C) ALKBH3, (D) ALKBH4, (E) ALKBH5, (F) ALKBH6, (G) ALKBH7, (H) ALKBH8 and (I) FTO on the abundance of immune cells in OV patients.

Figure 9

The methylation levels of the AlkB family in OV tissues. The methylation values of AlkB family members were evaluated using the DiseaseMeth database.