Abstract
Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide. Currently, alpha-fetoprotein (AFP) is used as a standard serum marker for the detection of HCC, but its sensitivity and specificity are unsatisfactory, and optimal diagnostic markers for cirrhosis are lacking. We previously reported that growth differentiation factor 15 (GDF15) was significantly induced in HCV-infected hepatocytes. This study aimed to investigate GDF15 expression and its correlation with hepatitis virus-related liver diseases. A total of 412 patients with various liver diseases were studied. Healthy and Mycobacterium tuberculosis-infected subjects were included as controls. Serum and tissue GDF15 levels were measured. Serum GDF15 levels were significantly increased in patients with HCC (6.66±0.67 ng/mL, p<0.0001) and cirrhosis (6.51±1.47 ng/mL, p<0.0001) compared with healthy controls (0.31±0.01 ng/mL), though the GDF15 levels in HBV and HCV carriers were moderately elevated (1.34±0.19 ng/mL and 2.13±0.53 ng/mL, respectively). Compared with HBV or HCV carriers, GDF15 had a sensitivity of 63.1% and a specificity of 86.6% at the optimal cut-off point of 2.463 ng/mL in patients with liver cirrhosis or HCC. In HCC patients, the area under the receiver operating curve was 0.84 for GDF15 and 0.76 for AFP, but 0.91 for the combined GDF15 and AFP. Serum GDF15 levels did not significantly differ between the high-AFP and low-AFP groups. GDF15 protein expression in HCC was significantly higher than that in the corresponding adjacent paracarcinomatous tissue and normal liver. Using a combination of GDF15 and AFP will improve the sensitivity and specificity of HCC diagnosis. Further research and the clinical implementation of serum GDF15 measurement as a biomarker for HCC and cirrhosis are recommended.
Highlights
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major risk factors for liver cirrhosis (LC) and hepatocellular carcinoma (HCC), which are the most common causes of end-stage liver disease
A clinical relevance has not been reported between serum growth differentiation factor 15 (GDF15) level and severe liver diseases, such as hepatocellular carcinoma and cirrhosis
We showed that GDF15, a divergent transforming growth factor β (TGF-β) superfamily member, was markedly increased in the serum of patients with HCC or LC
Summary
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major risk factors for liver cirrhosis (LC) and hepatocellular carcinoma (HCC), which are the most common causes of end-stage liver disease. The survival rate of HCC is 12–18% in USA depending on race, placing it among the cancers with the worst prognosis.[1] the prognosis can be significantly improved by early diagnosis and treatment. Patients suspected of having LC or HCC typically undergo clinical examinations, including abdominal CT and liver biopsy. CT can detect lesion growth, but it is only a surrogate marker and may delay addressing the diagnosis.[2] Liver biopsy is an accurate diagnostic method, but its associated disadvantages, including invasion and poor patient compliance, limit its broad application.[3] the characterization of novel non-invasive biomarkers for LC and HCC is urgently needed
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