BSG (CD147) Serum Level and Genetic Variants Are Associated with Overall Survival in Acute Myeloid Leukaemia

Piotr Łacina,Katarzyna Bogunia-Kubik,Martyna Stachowicz-Suhs,Aleksandra Butrym,Joanna Wietrzyk,Grzegorz Mazur,Eliza Turlej

doi:10.3390/jcm11020332

Abstract

Basigin (BSG, CD147) is a multifunctional protein involved in cancer cell survival, mostly by controlling lactate transport through its interaction with monocarboxylate transporters (MCTs) such as MCT1. Previous studies have found that single nucleotide polymorphisms (SNPs) in the gene coding for BSG and MCT1, as well as levels of the soluble form of BSG (sBSG), are potential biomarkers in various diseases. The goal of this study was to confirm BSG and MCT1 RNA overexpression in AML cell lines, as well as to analyse soluble BSG levels and selected BSG/MCT1 genetic variants as potential biomarkers in AML patients. We found that BSG and MCT1 were overexpressed in most AML cell lines. Soluble BSG was increased in AML patients compared to healthy controls, and correlated with various clinical parameters. High soluble BSG was associated with worse overall survival, higher bone marrow blast percentage, and higher white blood cell count. BSG SNPs rs4919859 and rs4682, as well as MCT1 SNP rs1049434, were also associated with overall survival of AML patients. In conclusion, this study confirms the importance of BSG/MCT1 in AML, and suggests that soluble BSG and BSG/MCT1 genetic variants may act as potential AML biomarkers.

Highlights

Introduction published maps and institutional affilAcute myeloid leukaemia (AML) is a haematologic malignancy associated with uncontrolled proliferation of immature leukemic blasts that can lead to bone marrow failure [1].It is the most commonly diagnosed acute leukaemia in adults and its prognosis remains poor, with the 5-year overall survival rate being only 25% [2]
We previously showed that single nucleotide polymorphisms (SNPs) can act as biomarkers in AML [46,47], and we identified some BSG and MCT1 variants that were associated with survival in multiple myeloma patients; most importantly, BSG allele rs4919859 C was associated with worse MM progression-free survival [25]
Our study shows that BSG and MCT1 are overexpressed in most AML

Summary

Introduction

Acute myeloid leukaemia (AML) is a haematologic malignancy associated with uncontrolled proliferation of immature leukemic blasts that can lead to bone marrow failure [1]. It is the most commonly diagnosed acute leukaemia in adults and its prognosis remains poor, with the 5-year overall survival rate being only 25% [2]. Basigin (BSG), known as cluster of differentiation 147 (CD147) and extracellular matrix metalloproteinase inducer (EMMPRIN), is a glycoprotein that belongs to the immunoglobulin superfamily It is a transmembrane protein commonly expressed on many human cell types and first identified as a stimulator of matrix metalloproteinase (MMP) production, it is known to be involved in many other cellular iations

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