The Clinical Role of Serum Epidermal Growth Factor Receptor 3 in Hepatitis C Virus-Infected Patients with Early Hepatocellular Carcinoma

SIMPLE SUMMARY: The identification of diagnostic and prognostic biomarkers for the management of patients with hepatocellular carcinoma is an unmet need. Here we investigate the potential clinical utility of the measurement of serum epidermal growth factor receptor 3 (i.e., ERBB3) in hepatitis C virus-infected patients with early hepatocellular carcinoma. Median values of serum ERBB3 were similar between patients with cirrhosis and those with early hepatocellular carcinoma (HCC); therefore, the measurement of the biomarker in the setting of HCC surveillance appeared unsuitable. Conversely, in patients with early HCC, serum ERBB3 values were significantly associated with overall survival, suggesting that the biomarker may be useful to tailor appropriate treatment strategies in hepatitis C virus (HCV)-infected patients with early hepatocellular carcinoma. ABSTRACT: Epidermal growth factor receptor 3 (ERBB3) is a surface tyrosine kinase receptor belonging to the EGFR/ERBB family, involved in tumor development and progression. We evaluated the diagnostic and prognostic value of serum ERBB3 measurement in hepatitis C virus (HCV)-infected patients with early hepatocellular carcinoma (HCC). A total of 164 HCV-infected patients (82 with cirrhosis and 82 with early HCC) were included in the study. HCC was classified according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Among patients with HCC, 23 (28%) had a diagnosis of very early tumor (BCLC = 0), while 59 (62%) had a diagnosis of early HCC (BCLC = A). Median overall survival (OS) in patients with HCC was 79.2 (95% CI 51.6–124.8) months. While ERBB3 serum values were similar between patients with cirrhosis and those with HCC (p = 0.993), in the latter, serum ERBB3 ≥ 2860 RU resulted significantly and independently associated with OS (Hazard Ratio = 2.24, 95% CI 1.16–4.35, p = 0.017). Consistently, the 1-, 3-, and 5-year OS rates in patients with serum ERBB3 ≥ 2860 RU were 90% (36/40), 53% (19/36), and 28% (8/29) in comparison to patients with serum ERBB3 < 2860 RU, which were 98% (40/41), 80% (32/40), and 74% (26/35) (Log-rank test; p = 0.014). In conclusion, serum ERBB3 values resulted an independent prognostic factor of patients with early HCC and might be useful to tailor more personalized treatment strategies.