Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Cancer Med. 2024 May;13(9):e7238. doi: 10.1002/cam4.7238.
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.
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.
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.
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.
肝内胆管癌(ICC)具有较高的复发率和较差的预后。因此,需要开发有效的治疗方法和预后生物标志物。二酰基甘油激酶α(DGKα)高表达是肝细胞癌复发的预后因素。然而,DGKα在 ICC 中的表达与预后的关系尚未报道。
对 ICC 手术标本(n=69)进行抗 DGKα 抗体免疫组织化学(IHC)检测。首先,将癌细胞中 DGKα 的表达定性分为 4 组(-、1+、2+、3+),并分为 2 组(DGKα-和 DGKα+1+至 3+)。分析临床特征与 DGKα 表达的关系。其次,评估 Ki-67 表达作为细胞增殖标志物。计数 Ki-67 阳性细胞的数量,并检查与 DGKα 表达的关系。
DGKα IHC 将患者分为 DGKα+组(1+:n=15;2+:n=5;3+:n=5)和 DGKα-组(-:n=44)。在 DGKα+组中,患者年龄较大且疾病进展。DGKα+患者的总生存率和无复发生存率(RFS)均显著降低。多因素分析显示,DGKα+是 RFS 的独立预后因素。此外,Ki-67 阳性细胞的数量与 DGKα 的染色水平呈正相关。
ICC 中病理性 DGKα 表达是与复发相关的癌增殖标志物。这表明 DGKα 可能是 ICC 的潜在治疗靶点。