Unveiling prognostics biomarkers of tyrosine metabolism reprogramming in liver cancer by cross-platform gene expression analyses

Abstract

Tyrosine is mainly degraded in the liver by a series of enzymatic reactions. Abnormal expression of the tyrosine catabolic enzyme tyrosine aminotransferase (TAT) has been reported in patients with hepatocellular carcinoma (HCC). Despite this, aberration in tyrosine metabolism has not been investigated in cancer development. In this work, we conduct comprehensive cross-platform study to obtain foundation for discoveries of potential therapeutics and preventative biomarkers of HCC. We explore data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Kaplan Meier plotter (KM plotter) and performed integrated analyses to evaluate the clinical significance and prognostic values of the tyrosine catabolic genes in HCC. We find that five tyrosine catabolic enzymes are downregulated in HCC compared to normal liver at mRNA and protein level. Moreover, low expression of these enzymes correlates with poorer survival in patients with HCC. Notably, we identify pathways and upstream regulators that might involve in tyrosine catabolic reprogramming and further drive HCC development. In total, our results underscore tyrosine metabolism alteration in HCC and lay foundation for incorporating these pathway components in therapeutics and preventative strategies.

Altered Serum Metabolic Profile Assessed by Advanced 1H-NMR in Breast Cancer Patients

“…Tyrosine could be used by BC cells as building blocks for proteins, as well as an alternative cellular energy source. As tyrosine metabolism is important for cancer progression, and according to our results, the tyrosine level could also be classified as a breast cancer risk factor [ 30 ]. The role of alanine in cancer is less well understood, but as an amino acid it could play a part in cancer cell proliferation and survival.…”

Loss of tyrosine catabolic enzyme HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer

“…The liver is the predominant organ where tyrosine catabolism takes place, which expresses the highest expression of tyrosine catabolic enzymes among other organs (Shiman and Gray, 1998). A recent study similarly reported the downregulation of tyrosine catabolic genes in HCC by comparing various publicly available datasets (Nguyen et al, 2020). However, these authors claimed that the expression of tyrosine catabolic genes was only significantly changed in late-stage HCC, but not in early-stage HCC, based on one independent GEO dataset.…”

Molecular Subtypes of Oral Squamous Cell Carcinoma Based on Immunosuppression Genes Using a Deep Learning Approach

“…In the present study, several signaling pathways related to metabolism were mainly enriched in subtype Sub2, for example, tyrosine metabolism, cytochrome p450 metabolism, and arachidonic acid metabolism. The downregulation of tyrosine metabolism pathway-related genes (HPD, HGD, GSTZ1, and FAH) was observed in hepatocellular carcinoma and indicated poor prognosis ( Nguyen et al, 2020 ); however, investigation of dysregulation of tyrosine metabolism pathways in OSCC is lacking. In addition, the inhibitor of tyrosine kinase, Imatinib, was shown to play both immunostimulatory and immunosuppressive role in the tumor immunology, an immunostimulatory role by stimulating the ability of dendritic cells and NK cells, and an immunosuppressive role by inhibiting the proliferation of T cells ( Nishioka et al, 2011 ).…”