Introduction
Hepatocellular Carcinoma (HCC) is a major type of primary liver cancer and one of the most frequent human malignant neoplasm. Owing to the lack of reliable clinical HCC markers, fewer than 20% of patients are diagnosed at a stage where curative treatment can be performed. Aldo-keto reductase family 1 member Bl0 (Akr 1 Bl0), cancer-related oxireductase was originally identified as a gene whose expression was upregulated in human HCC but was low in normal liver tissue. Akr l Bl0 upregulation was observed in several studies in certain chronic liver diseases such as chronic hepatitis B and C and steatohepatitis, which are widely recognized to represent a precancerous condition of HCC.
Aims & Methods
The aim is to investigate the role of serum AKR1B10 as a screening test for early detection of HCC in HCV related liver cirrhosis.
Methods: The study was carried out on 60 Egyptian patients with HCV related liver cirrhosis (Liver cirrhosis (LC) group: 30 patients with HCV related liver cirrhosis without HCC and HCC group: 30 patients with HCV related liver cirrhosis and HCC) and 20 healthy volunteers as controls from Menoufia University Hospitals (Egypt). They underwent history taking, physical examination and laboratory investigations (CBC, liver profile {ALT, AST, albumin, bilirubin, INR}, urea, creatinine, AFP, HBsAg, HCV Ab and serum AKR1B10). Abdominal ultrasonography was done for all patients and controls. HCC is further confirmed by triphasic CT. Patients with malignancy other than HCC, advanced HCC, received previous treatment for HCC, age <18 years old, HCC with distant metastasis and chronic liver disease other than HCV were excluded from the study.
Results
In HCC group, All patients had single lesion, 40% (n=12) in left lobe and 60% (n=18) in right lobe. HCC size was 5.7±2.5 cm (range 4.3 to 8.2 cm). No portal vein thrombosis was detected. In HCC group, according to BCLC classification, 22 patients (73.3%) were in A2 stage and 8 (26.7%) in A3 stage. According to TNM classification, all patients were in stage T1bN0M0. Serum AKR1B10 (pg/ml) was significantly higher in HCC group (3837.7±334.7) than LC (1176±187.7) and control group (664.7±402.2) (P˂0.001 for all). Also serum AKR1B10 (pg/ml) was significantly higher in LC group than in control group (P˂0.001). AFP level (ng/ml) was significantly higher in HCC group (6173±14080) than LC (12.7±5.6) and control group (7.2±4.3) (P˂0.001 for both). Also AFP level (ng/ml) was significantly higher in LC group than control group (P˂0.001). Serum AKR1B10 (pg/ml) at cutoff level >0.95 have 86.7% sensitivity and 70% specificity for detection of HCC. AFP at cutoff level >17.9 ng/ml have 67% sensitivity and 88% specificity for detection of HCC. Combined Serum AKR1B10 and AFP have 97.6% sensitivity and 100% specificity for detection of HCC. There was no significant difference between HCC and LC group as regard MELD score (19.6±0.5 and 19.5±0.5 respectively), APRI score (1.48±0.68 and 1.67±0.94 respectively), FIB-4 (2.05±1.79 and 2.35±2.26 respectively) and Child-Pugh score (6.3±1.5 and 5.9±0.3 respectively) (P˃0.05). In LC group, 27 patients (90%) were in Child class A, 3 patients (10%) were in Child class B. In HCC group, 24 patients (80%) were Child A, 6 patients (20%) were Child B.
Conclusion
AKR1B10 could be used as a diagnostic biomarker for early detection of HCC in HCV‑related cirrhosis, as it showed significant upregulation in patients with HCC in comparison with non‑HCC patients.
References
- Han C, Gao L, Bai H, Dou X. Identification of a role for serum aldo‑keto reductase family 1 member B10 in early detection of hepatocellular carcinoma. Oncol Lett. 2018;16(6):7123-30
-Murata, A, Genda, T, Ichida, T, Amano, N, Sato, S, et al. Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication. World J Gastroenterol. 2016;22(33):7569-78
- Mori M, Genda T, Ichida T, Murata A, Kamei M, Tsuzura H, et al. Aldo‐keto reductase family 1 member B10 is associated with hepatitis B virus‐related hepatocellular carcinoma risk. Hepatol Res. 2017;47(3):E85-93
-Jin J, Liao W, Yao W, Zhu R, Li Y, He S. Aldo-keto reductase family 1 member B 10 mediates liver cancer cell proliferation through sphingosine-1-phosphate. Sci Rep. 2016;6:22746
-Ye X, Li C, Zu X, Lin M, Liu Q, Liu J, et al. a large-scale multicenter study validates aldo-keto reductase family 1 member B10 as a prevalent serum marker for detection of hepatocellular carcinoma. Hepatology. 2019;69(6):2489-501
- Kanno M, Kawaguchi K, Honda M, Horii R, Takatori H, Shimakami T, et al. Serum aldo-keto reductase family 1 member B10 predicts advanced liver fibrosis and fatal complications of nonalcoholic steatohepatitis. J Gastroenterol. 2019;54(6):549- 57