Diacylglycerol kinase alpha is a proliferation marker of intrahepatic cholangiocarcinoma associated with the prognosis

Abstract

Abstract Background Intrahepatic cholangiocarcinoma (ICC) has a high recurrence rate and a poor prognosis. Thus, the development of effective treatment and prognostic biomarkers is required. High expression of diacylglycerol kinase alpha (DGKα) is a prognostic factor for the recurrence of hepatocellular carcinoma. However, the relationship between DGKα expression and prognosis in ICC has not been reported. Methods Immunohistochemistry (IHC) with anti‐DGKα antibody was performed on surgical specimens of ICC (n = 69). First, DGKα expression in cancer cells was qualitatively classified into four groups (−, 1+, 2+, 3+) and divided into two groups (DGKα− and DGKα+1 + to 3+). The relationship between clinical features and DGKα expression was analyzed. Second, Ki‐67 expression was evaluated as a cell proliferation marker. The number of Ki‐67‐positive cells was counted, and the relationship with DGKα expression was examined. Results DGKα IHC divided the patients into a DGKα+ group (1+: n = 15; 2+: n = 5; 3+: n = 5) and a DGKα− group (−: n = 44). In the DGKα+ group, patients were older and had advanced disease. Both overall survival and recurrence‐free survival (RFS) were significantly worse in the DGKα+ patients. DGKα+ was identified as an independent prognostic factor for RFS by multivariate analysis. Furthermore, the number of Ki‐67‐positive cells increased in association with the staining levels of DGKα. Conclusion Pathological DGKα expression in ICC was a cancer proliferation marker associated with recurrence. This suggests that DGKα may be a potential therapeutic target for ICC.

Keywords

• biomarker
• diacylglycerol kinase
• intrahepatic cholangiocarcinoma
• primary liver cancer
• prognostic factor