Glucose-transporter 1 (GLUT1) as a prognostic biomarker: evidence from 14,966 human tumors across 134 cancer types.

BACKGROUND: Glucose transporter 1 (GLUT1) is a key protein for transmembranous glucose uptake of cells which is often overexpressed in cancer. METHODS: To better comprehend the prevalence and role of GLUT1 expression in different cancer types, a tissue microarray containing 14,966 samples from 134 different tumor entities was analyzed in this study. GLUT1 expression was generally markedly higher in cancer than in corresponding normal tissues. RESULTS: A total of 122 of 134 tumor categories showed GLUT1 expression in at least 1 case, and 97 tumor categories included at least 1 case with strong GLUT1 staining. The frequency of GLUT1 positivity was particularly high in squamous cell carcinomas of various sites of origin (92.9%-100%), urothelial neoplasms (91.3%-98.7%), and carcinomas of the ovary and the endometrium (up to 100%). Elevated levels of GLUT1 staining were often associated with parameters of cancer aggressiveness. For example, high GLUT1 staining was associated with invasive growth of urothelial carcinomas (p = 0.0003), high grade (p = 0.0075), advanced pT stage (p = 0.025), and shorter survival (p = 0.0031) in clear cell renal cell carcinoma, high grade (p = 0.0500) and distant metastasis (p = 0.011), as well as shorter recurrence free survival (p = 0.0253) in papillary renal cell carcinoma, high grade in invasive breast cancer of no special type (p = 0.0003), advanced pT stage (p = 0.0008), nodal metastasis (p = 0.0007), V1 status (p = 0.004), and L1 status (p = 0.0008) in colorectal adenocarcinoma, and advanced pT stage (p = 0.0459) and MMR deficiency (p = 0.0018) in gastric cancer. CONCLUSIONS: It is concluded, that GLUT1 is highly expressed in a broad range of tumor entities, that it occurs more often in malignant than in benign tumors, and that it is linked to aggressive behavior in many different entities. These findings identify GLUT1 as a critical prognostic cancer marker, which may be clinically useful in many cancer types.