Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study
The Lancet Oncology,
Shen Q et al. – DKK1 could complement measurement of AFP in the diagnosis of HCC and improve identification of patients with AFP-negative HCC and distinguish HCC from non-malignant chronic liver diseases.
Methods- We analysed data for patients with HCC, chronic hepatitis B virus (HBV) infection, liver cirrhosis, and healthy controls, recruited from two Chinese centres between December, 2008, and July, 2009.
- A validation cohort matched for age and sex was recruited from another centre in China between July, 2010, and June, 2011.
- DKK1 was measured in serum by ELISA by independent researchers who had no access to patients' clinical information.
- We used receiver operating characteristics (ROC) to calculate diagnostic accuracy.
- We assessed serum DKK1 in 831 participants: 424 with HCC, 98 with chronic HBV infection, 96 with cirrhosis, and 213 healthy controls.
- The validation cohort comprised 453 participants: 209 with HCC, 73 with chronic HBV infection, 72 with cirrhosis, and 99 healthy controls.
- Levels of DKK1 in serum were significantly higher in patients with HCC than in all controls.
- ROC curves showed the optimum diagnostic cutoff was 2·153 ng/mL (area under curve [AUC] 0·848 [95% CI 0·820—0·875], sensitivity 69·1%, and specificity 90·6% in the test cohort; 0·862 [0·825—0·899], 71·3%, and 87·2% in the validation cohort).
- Similar results were noted for early-stage HCC (0·865 [0·835—0·895], 70·9%, and 90·5% in the test cohort; 0·896 [0·846—0·947], 73·8%, and 87·2% in the validation cohort).
- Furthermore, DKK1 maintained diagnostic accuracy for patients with HCC who were ?-fetoprotein (AFP) negative (0·841 [0·801—0·882], 70·4%, and 90·0% in the test cohort; 0·869 [0·815—0·923], 66·7%, and 87·2% in the validation cohort), including for patients with early-stage HCC (0·870 [0·829—0·911], 73·1%, and 90·0% in the test cohort; 0·893 [0·804—0·983], 72·2%, and 87·2% in the validation cohort), compared with all controls.
- Raised concentrations of DKK1 in serum could differentiate HCC from chronic HBV infection and cirrhosis (0·834 [0·798—0·871], 69·1%, and 84·7% in the test cohort; 0·873 [0·832—0·913], 71·3%, and 90·6% in the validation cohort).
- Moreover, measurement of DKK1 and AFP together improved diagnostic accuracy for HCC versus all controls compared with either test alone (0·889 [0·866—0·913], 73·3%, and 93·4% in the test cohort; 0·888 [0·856—0·920], 78·5%, and 87·2% in the validation cohort).
