Plasma lysophosphatidic acid levels and hepatocellular carcinoma

Abstract

We read with interest the article by Mazzocca et al.,1 showing that serum lysophosphatidic acid (LPA) levels are increased in hepatocellular carcinoma (HCC) patients correlated with tumor burden, while not enhanced in cirrhosis patients. However, we think that their LPA values in serum samples need to be carefully evaluated, because of some technical issues in the measurement of LPA levels in blood samples. First, because LPA is released from platelets, LPA has been measured in plasma but not in serum when evaluating its clinical significance.2, 3 Second, as we previously demonstrated,4 LPA levels in plasma samples are markedly increased after sample preparation unless the temperature is kept under strict control, potentially because the synthetic enzyme autotaxin (ATX) and the substrate lysophosphatidyl choline coexist in plasma samples to abundantly produce LPA. LPA was once reported as a biomarker of ovarian cancer,2 but contrary data were later demonstrated, in which a distinct sampling of plasma may explain this discrepancy.3 Indeed, LPA levels in serum reported by Mazzocca et al. were approximately 10 times higher than the previously reported LPA levels in plasma.2, 3 If their LPA values in serum were increased after sampling similarly in each sample, plasma LPA levels might be correlated with HCC burden as reported. To clarify this, we have newly measured plasma LPA levels in HCC patients, and found that they were not correlated with tumor burden, as shown in Fig. 1. Moreover, plasma LPA levels in HCC patients (0.12 ± 0.09 mM, mean ± SD, n = 21), were not different from the previously reported levels in non-HCC patients with chronic hepatitis C (0.10 ± 0.05 mM).5 Although Mazzocca et al. reported no enhancement of serum LPA levels in cirrhosis patients, we5 and others6 previously showed that plasma LPA levels and serum ATX activity were increased in chronic liver diseases in association with fibrosis and cholestatic pruritus, from which HCC frequently arises. Collectively, a role of LPA in HCC should be cautiously analyzed. Plasma LPA levels and HCC burden. Plasma LPA levels, measured in 21 HCC patients (13 males and 8 females; 2 patients with chronic hepatitis B, 15 with chronic hepatitis C, and 4 with non-B non-C chronic liver disease), were not significantly correlated with HCC burden as evaluated by RECIST (Response Evaluation Criteria in Solid Tumors; Spearman rank, r = 0.158, P = 0.4937). This study was approved by the Institutional Research Ethics Committee and informed consent was obtained for the use of the samples. Hitoshi Ikeda M.D., Ph.D.* , Kenichiro Enooku M.D. Ph.D.* , Ryunosuke Ohkawa Ph.D.*, Kazuhiko Koike M.D., Ph.D. , Yutaka Yatomi M.D., Ph.D.*, * Department of Clinical Laboratory Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.