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Association of serum level of growth differentiation factor 15 with liver cirrhosis and hepatocellular carcinoma.

Liu X, Chi X, Gong Q, Gao L, Niu Y, Chi X, Cheng M, Si Y, Wang M, Zhong J, Niu J, Yang W - PLoS ONE (2015)

Bottom Line: Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide.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.

View Article: PubMed Central - PubMed

Affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

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.

No MeSH data available.


Related in: MedlinePlus

Serum GDF15 level alterations in patients with hepatitis virus-related diseases.Scatter plots show the serum GDF15 levels in healthy subjects and patients with various liver diseases by ELISA. The black line indicates the mean, for which the value is indicated at the bottom of the scatter plot. The P values for HBV carriers vs. HBV cirrhosis, HBV carriers vs. HBV HCC and HCV carriers vs. HCV HCC are indicated.
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pone.0127518.g002: Serum GDF15 level alterations in patients with hepatitis virus-related diseases.Scatter plots show the serum GDF15 levels in healthy subjects and patients with various liver diseases by ELISA. The black line indicates the mean, for which the value is indicated at the bottom of the scatter plot. The P values for HBV carriers vs. HBV cirrhosis, HBV carriers vs. HBV HCC and HCV carriers vs. HCV HCC are indicated.

Mentions: A large proportion of HCC and cirrhosis cases are associated with chronic hepatitis virus infection, particularly HBV and HCV. To further investigate the relationship of GDF15 expression and hepatitis virus-related liver diseases, serum GDF15 values were measured in HBV carriers, HCV carriers and patients with HBV cirrhosis, HBV HCC, HCV cirrhosis or HCV HCC. As shown in Fig 2, moderate elevations of serum GDF15 were observed in HBV carriers and HCV carriers, with values of 1.34±0.19 ng/mL and 2.13±0.53 ng/mL (p = 0.1463), respectively. Notably, with the exception of HBV cirrhosis and HBV HCC, HBV HCC and HCV HCC and HBV cirrhosis and HCV HCC, the disease groups significantly differed from each other (p<0.001). In this study, due to the limitation of the small number of available HCV cirrhosis samples, the data of HCV cirrhosis was omitted in Fig 2. The highest GDF15 level was found in the HCV-positive HCC group. Chronic infection by microbes, such as hepatitis viruses and TB, often correlates with inflammation and immune cell dysfunction. To investigate the relationship between elevated GDF15 in hepatitis virus-related diseases and carcinogenesis or microbial infection, we analyzed the serum GDF15 levels in patients with active or latent TB infection. No statistically significant difference was observed between the healthy and TB groups, with GDF15 values of 0.31±0.02 ng/mL in healthy subjects, 0.35±0.01 ng/mL (p = 0.0532) in active TB patients and 0.28±0.01 ng/mL (p = 0.1089) in latent TB patients (Fig 3).


Association of serum level of growth differentiation factor 15 with liver cirrhosis and hepatocellular carcinoma.

Liu X, Chi X, Gong Q, Gao L, Niu Y, Chi X, Cheng M, Si Y, Wang M, Zhong J, Niu J, Yang W - PLoS ONE (2015)

Serum GDF15 level alterations in patients with hepatitis virus-related diseases.Scatter plots show the serum GDF15 levels in healthy subjects and patients with various liver diseases by ELISA. The black line indicates the mean, for which the value is indicated at the bottom of the scatter plot. The P values for HBV carriers vs. HBV cirrhosis, HBV carriers vs. HBV HCC and HCV carriers vs. HCV HCC are indicated.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4440744&req=5

pone.0127518.g002: Serum GDF15 level alterations in patients with hepatitis virus-related diseases.Scatter plots show the serum GDF15 levels in healthy subjects and patients with various liver diseases by ELISA. The black line indicates the mean, for which the value is indicated at the bottom of the scatter plot. The P values for HBV carriers vs. HBV cirrhosis, HBV carriers vs. HBV HCC and HCV carriers vs. HCV HCC are indicated.
Mentions: A large proportion of HCC and cirrhosis cases are associated with chronic hepatitis virus infection, particularly HBV and HCV. To further investigate the relationship of GDF15 expression and hepatitis virus-related liver diseases, serum GDF15 values were measured in HBV carriers, HCV carriers and patients with HBV cirrhosis, HBV HCC, HCV cirrhosis or HCV HCC. As shown in Fig 2, moderate elevations of serum GDF15 were observed in HBV carriers and HCV carriers, with values of 1.34±0.19 ng/mL and 2.13±0.53 ng/mL (p = 0.1463), respectively. Notably, with the exception of HBV cirrhosis and HBV HCC, HBV HCC and HCV HCC and HBV cirrhosis and HCV HCC, the disease groups significantly differed from each other (p<0.001). In this study, due to the limitation of the small number of available HCV cirrhosis samples, the data of HCV cirrhosis was omitted in Fig 2. The highest GDF15 level was found in the HCV-positive HCC group. Chronic infection by microbes, such as hepatitis viruses and TB, often correlates with inflammation and immune cell dysfunction. To investigate the relationship between elevated GDF15 in hepatitis virus-related diseases and carcinogenesis or microbial infection, we analyzed the serum GDF15 levels in patients with active or latent TB infection. No statistically significant difference was observed between the healthy and TB groups, with GDF15 values of 0.31±0.02 ng/mL in healthy subjects, 0.35±0.01 ng/mL (p = 0.0532) in active TB patients and 0.28±0.01 ng/mL (p = 0.1089) in latent TB patients (Fig 3).

Bottom Line: Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide.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.

View Article: PubMed Central - PubMed

Affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

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.

No MeSH data available.


Related in: MedlinePlus