OATP1A2 mRNA downregulation in canine hepatocellular carcinoma

Background On gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA) magnetic resonance imaging, canine hepatocellular carcinoma (HCC) and hepatocellular adenoma (HCA) typically exhibit low and high signal intensities in the hepatobiliary phase, respectively. Reduced transporter protein expression is associated with decreased Gd‐EOB‐DTPA uptake. However, the specific transporters involved in Gd‐EOB‐DTPA uptake in canine HCC remain unknown. This exploratory study aimed to assess the mRNA expression of transporters that are downregulated in canine HCC. Methods For the bioinformatics analysis, an RNA sequencing dataset comprising 14 canine HCC samples and four normal liver samples was obtained from the DDBJ BioProject repository. Differentially expressed genes (DEGs) were evaluated for members of the organic anion transporting polypeptides (OATP1‐6) family, multidrug resistance‐associated protein 2 (MRP2), bile salt export pump (BSEP), breast cancer resistance protein (BCRP), organic cation transporter 1 (OCT1) and multidrug resistance‐associated protein 3 (MRP3) in comparison between HCC and normal liver tissues. Genes with an absolute log‐fold change greater than 1 and a nominal p ‐value less than 0.05 were considered candidate DEGs. For clinical samples, surgically resected samples from eight canine HCCs and four canine HCAs were evaluated. RNA was extracted from the samples, and the expression levels of OATP1A2 were compared between HCCs and HCAs using real‐time quantitative polymerase chain reaction. Results In bioinformatics analysis, upregulated DEGs in HCC included OATP3A1/ SLCO3A1 and OATP5A1/ SLCO5A1 , whereas downregulated DEGs included OATP1A2/ SLCO1A2 . In clinical samples, OATP1A2 mRNA expression was significantly lower in HCC than in HCA ( p = 0.01). Conclusion Downregulation of OATP1A2 is associated with canine HCC and may contribute to reduced Gd‐EOB‐DTPA uptake.