Serum Dickkopf-1 (DKK1) is significantly lower in patients with lung cancer but is rapidly normalized after treatment

DKK1 is a secreted glycoprotein that inhibits Wnt/β-catenin signaling but may up-regulate the nonconani-cal Wnt signaling. Consistent with its inhibitory function in Wnt/β-catenin signaling, aberrant DKK1 expression has been observed in many types of human cancers, while contradicting findings have been reported in other studies. There are also several studies on serum DKK1 levels in various cancers with conflicting findings. In the present study, serum DKK1 was determined in 217 non-small cell lung cancer (NSCLC) patients, 35 small cell lung cancer (SCLC) patients and 286 matched healthy controls using a commercially available ELISA assay kit. Compared to healthy controls, serum DKK1 level was significantly lower in NSCLC (p < 10^-28) and SCLC (p <10^-4) patients. Interestingly, serum DKK1 level was higher in NSCLC patients in stage IV (p < 0.0005), with lymph node involvement (p < 0.0002) or with metastasis (p < 0.0001), suggesting that DKK1 may promote metastasis. After surgery and/or chemotherapy, serum DKK1 level is rapidly increased and reached levels observed in healthy controls in most patients. The degree of post therapeutic DKK1 increase varied in different treatment regimens. Our results thus provide strong evidence for the reduced levels of serum DKK1 in both types of lung cancer. However, in the context of all published studies, DKK1 appears to have a dichotomous role in cancer and its effect in a given cancer type or even a given cancer patient is likely to depend on the molecular context of the patient.