The usefulness of lactate dehydrogenase measurements in current oncological practice

Abstract

One of the hallmarks of cancer cells is increased energy requirements associated with the higher rate of cellular proliferative activity. Metabolic changes in rapidly dividing cancer cells are closely associated with increased uptake of glucose and abnormal activity of lactate dehydrogenase (LDH), which regulates the processing of glucose to lactic acid. As serum LDH levels were found to be commonly increased in cancer patients and correlated with poor clinical outcome and resistance to therapy, the determination of LDH has become a standard supportive tool in diagnosing cancers or monitoring the effects of cancer treatment. The aim of this review is to summarize the current knowledge about methods and the practical utility for measuring both the total LDH and LDH isoenzymatic activities in the diagnosis, prognosis and prediction of cancer diseases.

Keywords: LDH isoforms; Lactate dehydrogenase; Tumor markers; Warburg effect.

Fig. 1

Scheme showing the LDH reaction. LDH catalyzes the reversible conversion of pyruvate to lactate with NADH as a cofactor during glycolysis. The LD5 isoform preferentially catalyzes the reduction of pyruvate into lactate and thus prevents entry of pyruvate to the tricarboxylic acid (TCA) cycle. The NADH oxidation allows the regeneration of NAD+ molecules, which are needed for the continuous generation of ATP to maintain glycolysis. By contrast, the LD1 is predisposed to convert lactate into pyruvate with the concomitant generation of NADH

Fig. 2

Scheme presenting LDH isoforms. The ldha and ldhb genes encode LDHA and LDHB polypeptide subunits. The combinations of these two subunits into active tetramers results in the five LDH isoforms B4, A1B3, A2B2, A3B1 and A4, named LD1 to LD5, respectively. A third type of LDH subunit, known as C, is encoded by the ldhc gene. The LDHC subunit assembles only into homotetramers to form the LD6 (or LDX) isoform. The multiplicity of LDH molecular forms can be revealed on the basis of their different mobility in gel electrophoresis. The LD1 isoform has the highest and LD5 the lowest migration rate towards the anode, as demonstrated in zymograms