Serum DLK1 is a potential prognostic biomarker in patients with hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death in developing countries, especially in East Asia and South Africa, and the identification of new biomarkers for early diagnosis and prognosis is needed. Delta-like 1 homologue (Drosophila) (DLK1) is expressed in malignancies and promotes cancer cell stemness and tumourigenicity, which makes this molecule a potential target for therapies directed against cancer stem/progenitor cells. Here, we aimed to assess the predictive value of DLK1 as a diagnostic and prognostic biomarker in HCC. With this purpose, serum DLK1 levels were detected using an enzyme-linked immunosorbent assay (ELISA) in serum specimens from 397 HCC patients, 114 healthy individuals, 43 patients with chronic hepatitis B virus (HBV) infection and 24 cirrhotic liver patients with HBV infection, and the correlation between DLK1 levels and clinical features was evaluated. Our data showed that the serum DLK1 level was significantly higher in HCC patients than in healthy individuals or patients with chronic HBV infection (HBV carriers) (P < 0.05). Moreover, the serum DLK1 levels were positively correlated with tumour size and α-fetoprotein (AFP) levels, but not with gender, age, histological grade, HBV infection, intrahepatic metastasis or cirrhosis in HCC patients. Kaplan-Meier analysis indicated that higher DLK1 levels were associated with shorter survival in HCC patients. These results suggest that the serum levels of DLK1 may serve as a prognostic biomarker for HCC patients.

Targeting endogenous DLK1 exerts antitumor effect on hepatocellular carcinoma through initiating cell differentiation

“…Our previous study also indicated that DLK1 was overexpressed in 73.2% human HCC specimens because of the decreased DNA methylation on the promoter of DLK1 [19]. A recent study demonstrated serum DLK1 is a potential prognostic biomarker in HCC patients [26]. …”

Roles of DLK1 in Liver Development and Oncogenesis

“…Delta-like 1 homolog is expressed in malignancy and promotes cancer cell stemness and tumorigenicity so it can be used as therapeutic target and tumor marker for cancer stem/progenitor cells. Li et al (2015) revealed that tumor size of HCC was positively correlated to DLK1 in serum. DLK1 can be a complement to Alpha Feto Protein (AFP) in the diagnosis of HCC (Li et al, 2015;Chauhan and Lahiri 2016;Shen et al, 2016).…”

Advances in surface markers of liver cancer stem cell

“…Huang et al [154] demonstrated that proliferation of SMMC-7721 cells was significantly enhanced by exogenous DLK1, whereas colony-forming ability, cell growth, and tumorigenicity of Huh-7, Hep3B, and HepG2 cells were significantly impeded by the suppression of endogenetic DLK 1 via RNA interference. It was identified by Li et al [13] that the enhancing effect of DLK1 in tumourigenicity and cancer stemness could potentially be used as a molecule target for therapies against LCSCs. DLK1+ cells have been discovered in all 17 HCC cell lines and showed a more potent capability of clonogenicity in vitro and tumorigenicity in animal models.…”

“…In order to develop patient-specific therapies that target LCSCs, multiple stemness surface markers have been identified consisting CD133 [2] , CD44 [3] , CD90 [4] , epithelial cell adhesion molecule (EpCAM) [5] , CD47 [6] , CD34 [7] , C-kit [8] , CD13 [9] , CD24 [10] , calcium channel α2δ 1 isoform5 [11] , oval cell marker OV6 [12] , DLK1 [13] , K19 [14] , and Lgr5+ [15] [ Table 1]. The integrated therapy using conventional anti-carcinogenic inhibitors such as sorafenib with LCSCs-targeting drugs, may provide an effective therapeutic strategy for complete elimination of liver cancer.…”