Expression of Alanine-Serine-Cysteine Transporter 2 (ASCT2) and L-type Amino Acid Transporter 1 (LAT1) in Low-Grade and High-Grade Gliomas: An Analysis of Open-Access Immunohistochemical Data.

Background:  The amino acid transporters alanine-serine-cysteine transporter 2 (ASCT2) and L-type amino acid transporter 1 (LAT1) are the primary transporters of essential amino acids in cancer. ASCT2 and LAT1 are overexpressed in solid tumors and have been associated with poor survival. These transporters may hold prognostic significance and offer potential theranostic utility in the treatment of glioma. The aims of this study are twofold: (1) to determine whether ASCT2 and LAT1 mRNA expression are related to glioma grade and survival; and (2) to characterize ASCT2 and LAT1 expression in low-grade glioma (LGG) and high-grade glioma (HGG).

Methods:  Survival and mRNA expression data for both ASCT2 and LAT1 were obtained from The Cancer Genome Atlas (TCGA), accessed via the cBio Cancer Genomics Portal. GraphPad Prism was used to conduct a Kaplan-Meier survival analysis. Immunohistochemistry images were obtained from the Human Protein Atlas (HPA) database and analyzed with QuPath for ASCT2 and LAT1 expression in the cytoplasm and at the endothelium.

Results:  Query of TCGA resulted in 49 samples from 28 patients, which were evaluated for ASCT2 and LAT1 expression. Cytoplasmic staining of mRNA for ASCT2 and LAT1 was not associated with glioma grade or survival. Higher mRNA expression of ASCT2 correlated with worse survival (p=0.002) in LGG but not in HGG. mRNA expression of LAT1 did not have any prognostic value. QuPath analysis of samples from the HPA showed increased staining for both ASCT2 and LAT1 at the endothelium in both LGG and HGG. Endothelial expression of ASCT2 and LAT1 correlated with glioma grade.

Conclusion:  In our small study conducted with open-access data, ASCT2 and LAT1 did not appear to have prognostic value. However, both ASCT2 and LAT1 staining were increased at the endothelium compared to normal brain tissue. These amino acid transporters may play an important role in tumor proliferation and support theranostic approaches to glioma.