Evaluation of squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM) and alpha-l-fucosidase (AFU) as novel diagnostic biomarkers for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) surveillance lacks a reliable biomarker. Alpha-fetoprotein (AFP) is the most widely used. However, not all HCCs secrete AFP. AFP may be elevated with cirrhosis in the absence of HCC. Serum alpha-L-fucosidase (AFU) and squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IgM) were found to be useful markers in diagnosing HCC. SCCA-IgM and AFU were assessed by ELISA technique; AFP was measured by enzyme chemiluminescence in serum of 40 patients with HCC, 30 patients with liver cirrhosis, and 20 healthy control participants to compare their accuracy in early diagnosis of HCC. Serum SCCA-IgM and AFU levels were significantly elevated in HCC group compared to cirrhotic group (P value<0.001 and <0.001, respectively). Receiver operating characteristic curve showed the optimal cutoff value for SCCA-IgM was 233 AU/ml with sensitivity 87.5% and specificity 66% and for AFU was 25 U/L with sensitivity 87.5% and specificity 98%. AFP cutoff value was 48 ng/mL with sensitivity of 70% and specificity of 53.3%. The simultaneous determination of AFP and SCCA-IgM activity increased the sensitivity to 92.5% and specificity to 62.1%. There were positive significant correlations between SCCA-IgM and each of AFU (r=0.296, P=0.005) and AFP (r=0.284, P=0.007) and no correlation between AFP and AFU. All markers did not correlate with the tumor size or affected by the Child score. The significant difference between SCCA-IgM and AFU levels among HCC and cirrhotic patients suggests their use as potential diagnostic tools and allows identifying a new group of HCC patients even in the absence of elevated AFP.

Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis

“…The clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) in early prediction of HCC development in patients with chronic HBV or HCV infection was recently evaluated in a large Japanese study. Even at low AFP levels and in absence of suspicious ultrasound findings an elevation of hs-AFP-L3 was an early predictor of HCC development with an elevation in 34.3% of patients one year prior to diagnosis of HCC [27] . In patients with low AFP levels (< 20 ng/mL), the diagnostic sensitivity for hs-AFP-L 3% at a cut-off of 5% was 41.5% with a specificity of 85.1% [28] .…”

Serum DLK1 is a potential prognostic biomarker in patients with hepatocellular carcinoma

“…Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death, and over 80 % of HCC cases occur in developing countries [1][2][3]. Worldwide, HCC is a leading cause of cancerrelated mortality and has a very poor prognosis because it is rarely diagnosed at an early stage; moreover, the burden of this devastating cancer is expected to increase further in coming years [4].…”

Diagnostic accuracy of SCCA and SCCA‐IgM for hepatocellular carcinoma: A meta‐analysis

“…(Table ) The major bias identified in the studies was in “patient selection” and the “index test”. Four studies selected cirrhosis patients as the control group; seven studies included patients with hepatitis, chronic liver disease, or cirrhosis or healthy donors as the control group . Three studies did not included tumour biopsies to confirm HCC, and we marked one study as “unclear” …”

“…Lately, the progressive increase in SCCA and immunoglobulin M (SCCA‐IgM) has been associated with liver tumour development, suggesting that monitoring SCCA‐IgM levels might be useful for identifying cirrhotic patients at higher risk of developing HCC . Two studies performed in two different countries with distinct populations confirmed that SCCA and SCCA‐IgM levels have better diagnostic accuracy than AFP for the diagnosis of HCC . Moreover, a number of studies supported the usefulness of SCCA‐IgM for the diagnosis, prognosis and monitoring of chronic liver disease, including the histological response after antiviral treatments .…”

“…However, the results are controversial because of the different cut‐off values used in each study. Sensitivities ranged from 42% to 89% and specificities from 27% to 89%, with a wide range for the area under the curve (AUC) values, from 0.66 to 0.86 …”