Abstract
AKR1B10 is involved in hepatocarcinogenesis via modulation of fatty acid and lipid synthesis. AKR1B10 inhibition results in apoptosis of tumor cells whose lipids, especially phospholipids, were decreased by over 50%, suggesting involvement of phospholipids like sphingosine-1-phosphate (S1P) in AKR1B10’s oncogenic function. Using a co-culture system, we found that co-culture of QSG-7701 (human hepatocyte) with HepG2 (hepatoma cell line) increases QSG-7701’s proliferation, in which AKR1B10-S1P signaling plays a pivotal role. Consistent with previous findings, AKR1B10 mRNA and protein levels were higher in primary hepatocellular carcinoma (PHC) tissues than in peri-tumor tissues. Interestingly, the level of S1P was also higher in PHC tissues than in peri-tumor tissues. After analyzing the correlation between AKR1B10 mRNA expression in PHC tissues and the clinical data, we found that AKR1B10 mRNA expression was associated with serum alpha-fetoprotein (AFP), tumor-node-metastasis (TNM) stage, and lymph node metastasis, but not with other clinicopathologic variables. A higher AKR1B10 mRNA expression level is related to a shorter DFS (disease free survival) and OS (overall survival), serving as an independent predictor of DFS and OS in PHC patients with surgical resection.
Highlights
AKR1B10 is being considered as a biomarker candidate for PHC10,16, in that high AKR1B10 protein expression might be a favorable prognosis marker in primary hepatocellular carcinoma (PHC) patients who have had curative hepatectomy[17] or could reflect a less aggressive tumor behavior of PHC16
In agreement with these studies, this study showed that AKR1B10 mRNA level was higher in human PHC tissues than in peri-tumor tissues (99 in 144, 68.8%) and the protein level of AKR1B10 was higher in PHC tissues than in peri-tumor tissues
Consistent with a recent report that AKR1B10 is involved in hepatocarcinogenesis by modulating cell proliferation and apoptosis[5], we found that co-culture of QSG-7701 with HepG2 increases QSG-7701’s proliferation, and this increase is modulated by a higher level of cellular AKR1B10 in HepG2 than in QSG-7701
Summary
AKR1B10 is being considered as a biomarker candidate for PHC10,16, in that high AKR1B10 protein expression might be a favorable prognosis marker in PHC patients who have had curative hepatectomy[17] or could reflect a less aggressive tumor behavior of PHC16. Few studies have analyzed the relationship between AKR1B10 mRNA expression and PHC clinicopathological features. We measured AKR1B10 mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) and protein expression by immunohistochemical staining or Western blotting, and analyzed the correlation between changes in AKR1B10 mRNA expression and clinicopathologic features, or prognosis of patients with PHC
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