Prevalence and significance of PSAT1 expression in human cancer

Phosphoserine aminotransferase 1 (PSAT1) is an enzyme involved in de novo biosynthesis of L-serine by catalyzing the conversion of 3-phosphohydroxy-pyruvate to 3-phosphoserine. This reaction simultaneously produces alpha-ketoglutarate, thereby directly linking serine biosynthesis to glutamine metabolism, the tricarboxylic acid cycle and one carbon metabolism. L-serine is a vital substrate for numerous cellular processes such as the synthesis of proteins and neurotransmitters as well as nucleotide production and cell proliferation. Previous studies have linked PSAT1 upregulation to enhanced tumor cell proliferation, invasion and migration in various tumor entities, thereby suggesting a crucial role for PSAT1 in cancer development and progression. To learn more on the prevalence of PSAT1 expression and potential associations with phenotype across human malignancies, this study analyzed PSAT1 protein expression in a cohort of 14,966 tumor tissue samples from 134 different tumor entities in a tissue microarray format. PSAT1 staining was cytoplasmic and/or nuclear and occurred in various normal cell types and was seen in at least a fraction of cases in most tumor entities (124 of 134; 91.8%). Out of the 12,305 interpretable tumor samples, PSAT1 staining was found in 4,633 samples, including 3,168 (25.7%) with weak, 765 (6.2%) with moderate, and 700 (5.7%) with strong positivity. PSAT1 staining positivity was particularly frequent and high level in granular cell tumor (92.7%), urothelial carcinoma of the bladder (47.7-91.0%), embryonal carcinoma of the testis (88.4%), several subtypes of uterine cancer (65.1-87.5%), adrenal cortical adenoma and carcinoma (65.2-86.0%), ovarian cancer (15.4-84.6%), colorectal neuroendocrine carcinoma (63.3%), paraganglioma (63.3%), and in squamous cell carcinomas from different sites (50.6-62.2%). High PSAT1 expression was associated with unfavorable tumor phenotype in invasive breast carcinoma of no special type, clear cell renal cell carcinoma, papillary renal cell carcinoma, gastric adenocarcinoma, adenocarcinoma of the colon, and endometrioid endometrial carcinoma (p≤0.05 each). Low PSAT1 expression was associated with invasive tumor growth in urothelial carcinoma (p≤0.05 each). In conclusion, our data establish PSAT1 as a highly upregulated metabolic enzyme across a broad spectrum of human tumors. Its potential as both a prognostic biomarker and a therapeutic target is supported by an association with aggressive clinicopathological features in numerous tumor types.