Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?

Area of Science:

• Hepatology
• Oncology
• Biomarker Discovery

Background:

• Serum alpha-fetoprotein (AFP) is a standard tumor marker for hepatocellular carcinoma (HCC).
• A significant number of HCC patients present with normal AFP levels (N-HCC), even in advanced stages.
• The characteristics and diagnostic markers for N-HCC remain underexplored.

Purpose of the Study:

• To investigate the clinicopathological features of N-HCC.
• To evaluate the survival outcomes of N-HCC patients post-hepatectomy.
• To identify potential novel tumor markers for augmenting N-HCC diagnosis.

Main Methods:

• Retrospective analysis of 1616 HCC patients undergoing hepatectomy (2005-2015).
• Patients categorized into N-HCC (<15 ng/mL AFP) and abnormal AFP HCC (A-HCC) (≥15 ng/mL AFP).
• Kaplan-Meier, Cox regression, ELISA, and immunohistochemical (IHC) analyses were performed.

Main Results:

• 47.1% of HCC patients were classified as N-HCC.
• N-HCC patients were older, had more comorbidities, fewer hepatitis infections, smaller tumors, and less vascular invasion.
• N-HCC demonstrated significantly better disease-free survival (DFS) and overall survival (OS) compared to A-HCC.
• Glypican-3 (GPC3) emerged as a promising marker for N-HCC diagnosis via ELISA and IHC.

Conclusions:

• N-HCC exhibits distinct clinicopathological characteristics, including older age, less hepatitis/cirrhosis, and better tumor differentiation.
• The oncogenesis of N-HCC may differ from typical HCC.
• GPC3 is a potential tumor marker for diagnosing N-HCC, warranting further validation.