Biological roles of THRAP3, STMN1 and GNA13 in human blood cancer cells

Abstract

Blood cancers, such as diffuse large B-cell lymphoma (DLBCL), Burkitt's lymphoma (BL) and acute myeloid leukemia (AML), are aggressive neoplasms that are characterized by undesired clinical courses with dismal survival rates. The objective of the current work is to study the expression THRAP3, STMN1 and GNA13 in DLBCL, BL and AML, and to investigate if these proteins are implicated in the prognosis and progression of the blood cancers. Isolation of normal blood cells was performed using lymphoprep coupled with gradient centrifugation and magnetic beads. Flow-cytometric analysis showed high quality of the isolated cells. Western blotting identified THRAP3, STMN1 and GNA13 to be overexpressed in the blood cancer cells but hardly detected in normal blood cells from healthy donors. Consistently, investigations performed using genotype-tissue expression (GTEx) and gene expression profiling interactive analysis (GEPIA) showed that the three proteins had higher mRNA expression in various cancers compared with matched normal tissues (p ≤ 0.01). Furthermore, the up-regulated transcript expression of these proteins was a feature of short overall survival (OS; p ≤ 0.02) in patients with the blood cancers. Interestingly, functional profiling using gProfiler and protein-protein interaction network analysis using STRING with cytoscape reported THRAP3 to be associated with cancer-dependent proliferation and survival pathways (corrected p ≤ 0.05) and to interact with proteins (p = 1 × 10^-16) implicated in tumourigenesis and chemotherapy resistance. Taken together, these findings indicated a possible implication of THRAP3, STMN1 and GNA13 in the progression and prognosis of the blood cancers. Additional work using clinical samples of the blood cancers is required to further investigate and validate the results reported here.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04093-5.

Keywords: Blood cancers; GNA13; STMN1; THRAP3.