DKK1 boosts liver cancer diagnostic options

By Laura Cowen

Measurement of the protein Dickkopf-1 (DKK1) in serum could be used to diagnose hepatocellular carcinoma (HCC), especially early disease, Chinese researchers report.

DKK1 will help "resolve the deficiencies" of α-fetoprotein (AFP), which is currently the most widely used biomarker for HCC diagnosis, say the researchers. Such deficiencies include low sensitivity and the inability to distinguish HCC from chronic hepatitis and cirrhosis in up to half of all cases.

Wenxin Qin (Shanghai Jiao Tong University School of Medicine) and colleagues have previously shown that DKK1 is overexpressed in HCC tissue, but is not detectable in corresponding noncancerous liver tissue. In the present study, they investigated its potential as a diagnostic marker for HCC.

The researchers used receiver operating characteristic (ROC) analysis to calculate the optimum DKK1 cutoff concentration in a test cohort of 424 HCC patients and 407 non-HCC controls (213 healthy controls, 98 with chronic hepatitis B virus [HBV], and 96 with liver cirrhosis).

At the optimal cutoff of 2.153 ng/mL, DKK1 alone or in combination with AFP was better than AFP alone for distinguishing between patients with and without HCC. The respective area under the ROC curves (AUC) were 0.848, 0.889, and 0.830.

Similar results were noted for the detection of early-stage HCC versus the three control groups, with AUCs of 0.865, 0.905, and 0.819 for DKK1 alone, DKK1 plus AFP, and AFP alone, respectively.

Furthermore, DKK1 maintained diagnostic accuracy for patients with HCC who were AFP-negative (AUC=0.841), including for patients with early-stage HCC (AUC=0.870), compared with all controls.

The sensitivity of DKK1 alone ranged from 68% to 73%, while specificity ranged from 85% to 91%.

"This [specificity] rate is unacceptable for diagnostic tools in oncology, where they have to show almost 100% specificity," write Alejandro Forner and Jordi Bruix, from the University of Barcelona, in Spain, in an accompanying commentary.

Although there is "still a long way to go before DKK1 can be accepted as a diagnostic tool… [the study] adds a new piece of the puzzle of HHC diagnosis and opens the door for further investigations of this promising tumor biomarker," they say.

Qin et al note that they validated their findings in a cohort of 209 patients with HCC and 244 controls. However, they agree that the "diagnostic value of HCC still needs further investigation." This is because the study was based in China where most cases of HCC are related to cirrhosis or HBV infection, which is not the case in the USA, Europe, and Japan.

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