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

Cancer Med. 2024 May;13(9):e7238. doi: 10.1002/cam4.7238.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bile Duct Neoplasms* / metabolism
  • Bile Duct Neoplasms* / mortality
  • Bile Duct Neoplasms* / pathology
  • Biomarkers, Tumor* / metabolism
  • Cell Proliferation*
  • Cholangiocarcinoma* / metabolism
  • Cholangiocarcinoma* / mortality
  • Cholangiocarcinoma* / pathology
  • Diacylglycerol Kinase* / genetics
  • Diacylglycerol Kinase* / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen* / metabolism
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Prognosis

Substances

  • Diacylglycerol Kinase
  • Biomarkers, Tumor
  • Ki-67 Antigen