CD24 as a Novel Predictive Biomarker in Patients with Hepatocellular Carcinoma: Friend or Foe?

This article refers to:

Clinicopathological and Prognostic Value of Plasma CD24 Level in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) constitutes the most common primary hepatic cancer and remains a major medical burden in both developing and developed world [1]. In 2012, the new cases diagnosed and deaths recorded exceeded 780,000 and 740,000, respectively [2]. Overall, HCC constitutes the 3rd leading cause of cancer-related death, while its incidence and mortality are expected to rise within the following years [3–6]. Notably, the incidence of HCC in the United States (US) rose from 1.4 between 1976 and 1980 to 6.2 cases per 100,000 habitants in 2011 [4],[7]. Notwithstanding the significant progress noted in the development of diagnostic modalities as well as surgical techniques and surveillance programs, survival of patients diagnosed with HCC is disappointingly low [1]. Additionally, as far as the economic consequences of HCC are concerned, it has been demonstrated that the annual cost of HCC in the US is approximately 455 million dollars per year [8]. In that setting, novel diagnostic and predictive modalities are needed for diagnosis and treatment of HCC in the era of precision medicine.

The diagnostic and prognostic accuracy of several biomarkers has been thoroughly investigated during the last decades. Alpha fetoprotein (AFP) is currently the most widely used serum biomarker for surveillance and early diagnosis of patients with HCC [1],[3]. Regardless, its accuracy has been widely questioned with reported sensitivity and specificity of approximately 60% and 80%, respectively. Moreover, a number of other biomarkers have been proposed as alternatives including glycipan 3, serum Golgi protein 73, and des-gamma carboxyprothrombin but further studies have failed to demonstrate superior results to those of AFP [9–11].

Liver is an immunoprivileged organ biased to tolerance. There are many theories for this vital property. First, tolerance could be attributed to continuous exposure to antigens via portal vein, that promotes the expression of a set of cytokines, antigen-presenting molecules and co-stimulatory signals that impose T-cell inactivation, partly via effects on liver antigen presenting cells [12–14]. This property facilitates the organ to maintain homeostasis with a concomitant price being paid; that of vulnerability to viral infections, autoimmune diseases and carcinogenesis [15,16]. There is an increasing body of literature supporting the role of cluster of differentiation (CD) 24 as a biomarker for cancer diagnosis and prognosis. It seems that CD24 is overexpressed in many types of tumor tissues, including hematopoietic (B-cell lymphomas) as well as solid organ malignancies such as esophageal squamous cell carcinoma, HCC, cholangiocarcinoma, and pancreatic adenocarcinoma [17]. Interestingly, CD24 expression is significantly higher in invasive carcinoma than in precancerous lesions [18]. The causative role of CD24 in liver carcinogenesis is not fully understood; nevertheless, it seems that the epithelial-mesenchymal transition (EMT) and Notch1 signaling activations mediated by CD24 are potential mechanisms favoring the development of HCC [19]. In addition, Twist2-CD24-STAT3-Nanog pathway seems to play a critical role in regulating liver cancer stem-like cell self-renewal [20].

In their study entitled “Clinicopathological and Prognostic Value of Plasma CD24 Level in Hepatocellular Carcinoma”, the authors sought to evaluate the relevance of plasma CD 24 levels with clinicopathological features of HCC as well as delineate its prognostic value [21]. The study demonstrated that plasma CD24 levels were significantly higher in patients with HCC compared to healthy individuals and showed a significant association with tumor differentiation. More importantly, the authors demonstrated that plasma CD24 was a prognostic factor for overall and recurrence-free survival. Maybe the most critical finding lies in their subgroup analysis, where patients with low AFP values and high CD24 values had significantly worse survival than those with low CD24. This finding is of paramount importance, considering the variable accuracy of AFP levels in the clinical setting yielding CD24 levels as an emerging and potentially reliable diagnostic and prognostic biomarker in AFP negative HCC patients.

Although their study is partly limited by its retrospective nature and the small number of included patients, we commend the authors on this work and the potential reflections of their study. In view of the rising incidence of HCC worldwide, there is an urgent need for accurate biomarkers in an effort to achieve early stage diagnosis and improve life expectancy of these patients. Future studies with larger cohorts are essential in order to elucidate the diagnostic and prognostic utility of plasma CD24 levels in patients with HCC.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.