Expression profile of CD98 heavy chain and L-type amino acid transporter 1 and its prognostic significance in colorectal cancer

L-type amino acid transporter (LAT1) is a neutral amino acid transporter, forming a heterodimer complex with the CD98 heavy chain (CD98hc). In this study, we studied the expression profiles of LAT1 and CD98hc in colorectal cancer (CRC) and its precursor lesions. Transcription levels of CD98hc and LAT1 were significantly increased in CRC compared to the matched normal mucosa. CD98hc and LAT1 expression showed no significant correlations with cancer stem cell markers and intestinal stem cell markers, whereas both had positive correlations with Wnt target genes, AXIN2, and EPHB2, suggesting an association with aberrant Wnt signaling activation. Immunohistochemical analysis revealed that CD98hc and LAT1 are not expressed in normal colonic mucosa and various benign lesions including hyperplastic polyps and sessile and traditional serrated adenomas. CD98hc and LAT1 expressions began to appear in tubular adenomas and further increased in carcinomas. Of interest, CD98hc expression decreased during lymph node metastasis. Survival analysis demonstrated that CD98hc and LAT1 have no significant prognostic effect in CRCs. In conclusion, CD98hc and LAT1 are not normally expressed in colonic mucosa and most benign lesions. Their expression began to appear in tubular adenomas and further increased during the adenoma-to-carcinoma transition. CD98hc expression decreased while metastasizing to regional lymph nodes. However, CD98hc and LAT1 expressions had no prognostic value in patients with CRC.