High expression of Janus kinase 2 in background normal liver tissue of resected hepatocellular carcinoma is associated with worse prognosis

Abstract

When assessing hepatocellular carcinoma (HCC), it is important to examine prognostic factors in the background normal liver tissue and consider malignant aspects of the primary lesion. Candidate genes were extracted from the background normal liver samples via multiarray analysis. Control samples, termed supernormal (SN) liver, were obtained from 11 cases of metastatic liver cancer. Corresponding normal (CN) liver tissue was surgically obtained from a typical HCC patient with chronic hepatitis C background for comparison. Expression profile and methylation array demonstrated that Janus kinase 2 (JAK2) gene expression was increased by 2.378-fold in the CN tissue. Methylation array reported a lower value for CN (0.125) than SN tissues (0.748). We then investigated JAK2 expression by real-time quantitative reverse transcription-polymerase chain reaction in 100 consecutive resected HCC cases. The average expression level of JAK2 (normalized to GAPDH) was significantly lower in CN (9.24±6.43, n=100) than in SN (35.21±21.38, n=11) tissues (P<0.001). As such a result was contrary to our expectation, the case used for array analysis seemed to be a rare incidence. One hundred HCC cases were subsequently divided into two groups based on JAK2 expression in the adjacent normal tissue: one consisting of the upper 70% of cases (n=70) and the other of the remaining 30% (n=30). Higher JAK2 expression in the adjacent tissue demonstrated significant correlation with worse survival (P=0.022). Furthermore, multivariate analysis identified higher JAK2 expression in the background normal liver tissue of HCC as an independent prognostic factor (P=0.032). Our findings suggest that higher JAK2 expression in the background normal liver tissue of HCC may be a good prognostic biomarker for resected HCC.