Assessment of the Clinical Utility of Glypican 3 as a Serum Marker for the Diagnosis of Hepatocellular Carcinoma

Abstract

Glypican-3 has been reported to be one of the most promising serum markers for hepatocellular carcinoma. This study aimed to assess the clinical utility of serum glypican 3 for the diagnosis of hepatocellular carcinoma. We recruited consecutive patients on a large scale, 283 with hepatocellular carcinoma, 445 with chronic hepatic diseases, and 162 normal controls, to assess the diagnostic accuracy of serum glypican 3 for hepatocellular carcinoma by enzyme-linked immunosorbent assay. In addition, we further analyzed the relationship between the serum levels of a-fetoprotein and glypican-3 in patients with hepatocellular carcinoma. The results indicated that serum glypican 3 was elevated in patients with hepatocellular carcinoma (0 ng/mL, range ¼ 0-14.0 ng/mL, P ¼ .033) and liver cirrhosis (0 ng/mL, range ¼ 0-12.5 ng/mL, P ¼ .001) compared to the levels in normal control (0 ng/mL, range ¼ 0-4.3 ng/mL), but there was no difference between hepatocellular carcinoma and liver cirrhosis (P ¼ .097). The area under the curve of the receiver-operating characteristics curve for hepatocellular carcinoma versus all controls was 0.519, with a sensitivity of 39.9%, a specificity of 60.6%, and an optimal cutoff value of 0.002 ng/mL. The positive and negative predictive values were 32.0% and 68.3%, respectively. No significant correlation in serum levels was observed between glypican 3 and a-fetoprotein (P > .05). The diagnostic sensitivity for hepatocellular carcinoma increased to 72.8% (206 of the 283) when glypican 3 was combined with a-fetoprotein. Glypican 3 was not a promising serum maker for the diagnosis of hepatocellular carcinoma alone, but it could be complementary to a-fetoprotein and elevate the sensitivity of hepatocellular carcinoma diagnosis.

Glypican 3 as a Serum Marker for Hepatoblastoma

“…Several studies have confirmed the expression of GPC3 in regenerative nodules, hepatitis C samples, cirrhosis and even in normal liver tissues1935. In a recent study, Yasuda et al 27.…”

“…Some found that GPC3 is a more sensitive and specific serum marker than AFP for HCC1617182526. Conversely, others showed that GPC3 is not a good serum marker for HCC1927282930. As a result, the diagnostic value of serum GPC3 in patients with HCC remains controversial.…”

“…GPC3 levels were measured with a human GPC3 DuoSet enzyme-linked immunosorbent assay (ELISA) development kit (catalog number: DY2119; R&D Systems, Minneapolis, MN, USA) following the manufacturer’s instructions19. Briefly, a 96-well microplate was coated with the monoclonal antibody to GPC3 and incubated overnight, and then washed.…”

GPC-HCC model: a combination of glybican-3 with other routine parameters improves the diagnostic efficacy in hepatocellular carcinoma

“…This was indicated by both real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry [23]. However, when GPC3 is compared to AFP, the serum GPC3 diagnostic value in HCC remains controversial [14]. The virus infection, HCV or HBV, and GPC3 antibody source were not the culprits for this conflict.…”

“…In contrast to the hepatocytes of healthy individuals and hepatitis patients, many studies reported an increased GPC3 expression in HCC tissues [9]. However, many studies suggested that serum GPC3 is a specific HCC biomarker owing to its higher levels in HCC than that in healthy or hepatitis individuals [10,11]; conflicting results were obtained by other studies [12][13][14]. There is an agreement between most of these studies and others that GPC3 alone is not a promising HCC serum maker.…”