Oikawa Tsunekazu, Yamada Kohji, Tsubota Akihito, Saeki Chisato, Tago Naoko, Nakagawa Chika, Ueda Kaoru, Kamioka Hiroshi, Taniai Tomohiko, Haruki Koichiro, Nakano Masanori, Torisu Yuichi, Ikegami Toru, Yoshida Kiyotsugu, Saruta Masayuki
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan.
Gastro Hep Adv. 2022 Aug 5;2(1):83-95. doi: 10.1016/j.gastha.2022.07.020. eCollection 2023.
Hepatocellular carcinoma (HCC) is the most common cancer with a poor prognosis. Identification of an alternative biomarker that can detect early-stage and conventional tumor marker-negative HCC is urgently needed. We found that protein kinase C delta (PKCδ) is specifically secreted from HCC cell lines into extracellular space and contributes to tumor development and that its serum levels were elevated in HCC patients. This study aimed to assess the practical usefulness of serum PKCδ for detecting HCC in chronic liver disease (CLD) patients.
Serum PKCδ levels in 313 CLD patients with and without HCC (n = 187 and 126, respectively) were measured using a sandwich enzyme-linked immunosorbent assay. The diagnostic performance of PKCδ for HCC was evaluated using the receiver operating characteristic curve analysis and was compared with that of conventional markers, α-fetoprotein (AFP), and des-γ-carboxy prothrombin (DCP).
Serum PKCδ levels in HCC patients were significantly higher than those in CLD patients without HCC. PKCδ distinguished HCC patients from CLD patients without HCC, with high sensitivity and specificity. Subgroup analyses revealed that the diagnostic performance of PKCδ for HCC was comparable to that of AFP and DCP, and that approximately 40% of AFP/DCP double-negative HCC patients were positive for PKCδ. PKCδ yielded better diagnostic performance for detecting solitary small-sized (ie, very early stage) HCC than AFP and DCP. There was no significant correlation between serum PKCδ and AFP/DCP levels.
Serum PKCδ is a novel HCC biomarker, which is independent of and complementary to conventional markers. Specifically, PKCδ may be useful for detecting very early-stage or AFP/DCP double-negative HCC.
肝细胞癌（HCC）是最常见的癌症，预后较差。迫切需要鉴定一种能够检测早期以及传统肿瘤标志物阴性的HCC的替代生物标志物。我们发现蛋白激酶Cδ（PKCδ）可从HCC细胞系特异性分泌至细胞外空间并促进肿瘤发展，且其血清水平在HCC患者中升高。本研究旨在评估血清PKCδ在慢性肝病（CLD）患者中检测HCC的实际应用价值。
采用夹心酶联免疫吸附测定法检测313例有或无HCC的CLD患者（分别为187例和126例）的血清PKCδ水平。使用受试者工作特征曲线分析评估PKCδ对HCC的诊断性能，并与传统标志物甲胎蛋白（AFP）和异常凝血酶原（DCP）进行比较。
HCC患者的血清PKCδ水平显著高于无HCC的CLD患者。PKCδ以高灵敏度和特异性区分HCC患者与无HCC的CLD患者。亚组分析显示，PKCδ对HCC的诊断性能与AFP和DCP相当，约40%的AFP/DCP双阴性HCC患者PKCδ呈阳性。PKCδ在检测孤立小尺寸（即极早期）HCC方面比AFP和DCP具有更好的诊断性能。血清PKCδ与AFP/DCP水平之间无显著相关性。
血清PKCδ是一种新型HCC生物标志物，独立于传统标志物且与之互补。具体而言，PKCδ可能有助于检测极早期或AFP/DCP双阴性HCC。
