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

Author:

Shichi Shunsuke1ORCID,Sugiyama Ko1,Asahi Yoh1,Shirakawa Chisato1,Nakamoto Hiroki1,Kimura Saori1,Wakizaka Kazuki1ORCID,Aiyama Takeshi1,Nagatsu Akihisa1,Orimo Tatsuya1,Kakisaka Tatsuhiko1,Taketomi Akinobu1

Affiliation:

1. Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan

Abstract

AbstractBackgroundIntrahepatic 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.MethodsImmunohistochemistry (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.ResultsDGKα 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.ConclusionPathological DGKα expression in ICC was a cancer proliferation marker associated with recurrence. This suggests that DGKα may be a potential therapeutic target for ICC.

Funder

Japan Agency for Medical Research and Development

Ono Pharmaceutical

Ministry of Education, Culture, Sports, Science and Technology

Publisher

Wiley

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