Dissecting the biological diversity of hepatocellular carcinoma: Opening Pandora's Box

Primary liver cancer is one of the most commonly occur-ring malignancies, albeit one with a deadly consequence as it ranks second in males and sixth in females as a cause of cancer-related death [1, 2]. In this regard, hepatocellular carcinoma (HCC) constitutes almost 90% of confirmed primary liver cancer cases [3]. Despite the advances in clinical classifications of HCC according to patient-related and disease-related criteria (e.g., the Barcelona Clinic liver cancer system) [4], exploring the biological diversity of HCC have lagged behind. The biological diversity of HCC is ex-pected to come from a diverse set of etiological factors (Hepatitis-B virus, Hepatitis-C virus, non-alcoholic stea-tohepatitis, and aflatoxin, among other things), all of which are expected to drive the pathogenesis of HCC via various pathways. In the current issue of AMOR, Youssef and co-workers explored the potential involvement of the cofactor of BRCA1 (COBRA1) in HCC pathogenesis [5]. COBRA1 has been incriminated in the pathogenesis of a number of other solid tumors, notably breast cancer. In the current study, the authors investigated the expression of COBRA1 in several HCC cell lines, ranging from low- to high-grade HCC cell lines. Their results showed that the COBRA1 protein was highly expressed in the low-grade HCC cell line, while significantly down-regulated in high-grade HCC cell lines. This preliminary study indicates that COBRA1 may indeed play a role in HCC pathogenesis and progression, and should be further investigated moving forward. Primary liver cancer is one of the most commonly occurring malignancies, albeit one with a deadly consequence as it ranks second in males and sixth in females as a cause of cancer-related death [1,2]. In this regard, hepatocellular carcinoma (HCC) constitutes almost 90% of confirmed primary liver cancer cases [3]. Despite the advances in clinical classifications of HCC according to patient-related and disease-related criteria ( e.g. , the Barcelona Clinic liver cancer system) [4], exploring the biological diversity of HCC have lagged behind. The biological diversity of HCC is expected to come from a diverse set of etiological factors (Hepatitis-B virus, Hepatitis-C virus, non-alcoholic steatohepatitis, and aflatoxin, among other things), all of which are expected to drive the pathogenesis of HCC via various pathways. In the current issue of AMOR, Youssef and co-workers explored the potential involvement of the cofactor of BRCA1 (COBRA1) in HCC pathogenesis [5].  COBRA1 has been incriminated in the pathogenesis of a number of other solid tumors, notably breast cancer. In the current study, the authors investigated the expression of COBRA1 in several HCC cell lines, ranging from low- to high-grade HCC cell lines. Their results showed that the COBRA1 protein was highly expressed in the low-grade HCC cell line, while significantly down-regu- lated in high-grade HCC cell lines. This preliminary study indicates that COBRA1 may indeed play a role in HCC pathogenesis and progression, and should be further investigated moving forward.