Protein Kinase C Delta Is a Novel Biomarker for Hepatocellular Carcinoma

Backgrounds and Aims: 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 secr...

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Main Authors: Tsunekazu Oikawa, Kohji Yamada, Akihito Tsubota, Chisato Saeki, Naoko Tago, Chika Nakagawa, Kaoru Ueda, Hiroshi Kamioka, Tomohiko Taniai, Koichiro Haruki, Masanori Nakano, Yuichi Torisu, Toru Ikegami, Kiyotsugu Yoshida, Masayuki Saruta
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Gastro Hep Advances
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2772572322001340
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author Tsunekazu Oikawa
Kohji Yamada
Akihito Tsubota
Chisato Saeki
Naoko Tago
Chika Nakagawa
Kaoru Ueda
Hiroshi Kamioka
Tomohiko Taniai
Koichiro Haruki
Masanori Nakano
Yuichi Torisu
Toru Ikegami
Kiyotsugu Yoshida
Masayuki Saruta
author_facet Tsunekazu Oikawa
Kohji Yamada
Akihito Tsubota
Chisato Saeki
Naoko Tago
Chika Nakagawa
Kaoru Ueda
Hiroshi Kamioka
Tomohiko Taniai
Koichiro Haruki
Masanori Nakano
Yuichi Torisu
Toru Ikegami
Kiyotsugu Yoshida
Masayuki Saruta
author_sort Tsunekazu Oikawa
collection DOAJ
description Backgrounds and Aims: 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. Methods: 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). Results: 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. Conclusion: 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.
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spelling doaj.art-cf131429236646858d07c3fc33c2c03e2022-12-22T04:38:16ZengElsevierGastro Hep Advances2772-57232023-01-01218395Protein Kinase C Delta Is a Novel Biomarker for Hepatocellular CarcinomaTsunekazu Oikawa0Kohji Yamada1Akihito Tsubota2Chisato Saeki3Naoko Tago4Chika Nakagawa5Kaoru Ueda6Hiroshi Kamioka7Tomohiko Taniai8Koichiro Haruki9Masanori Nakano10Yuichi Torisu11Toru Ikegami12Kiyotsugu Yoshida13Masayuki Saruta14Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan; Correspondence: Address correspondence to: Tsunekazu Oikawa, MD, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato, Tokyo 105-8461, Japan.Department of Biochemistry, The Jikei University School of Medicine, Tokyo, JapanCore Research Facilities, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDepartment of Biochemistry, The Jikei University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision 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, JapanDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, JapanDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, JapanDepartment of Biochemistry, The Jikei University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanBackgrounds and Aims: 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. Methods: 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). Results: 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. Conclusion: 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.http://www.sciencedirect.com/science/article/pii/S2772572322001340HCCPKCδBiomarkerTumor MarkerEarly Detection
spellingShingle Tsunekazu Oikawa
Kohji Yamada
Akihito Tsubota
Chisato Saeki
Naoko Tago
Chika Nakagawa
Kaoru Ueda
Hiroshi Kamioka
Tomohiko Taniai
Koichiro Haruki
Masanori Nakano
Yuichi Torisu
Toru Ikegami
Kiyotsugu Yoshida
Masayuki Saruta
Protein Kinase C Delta Is a Novel Biomarker for Hepatocellular Carcinoma
Gastro Hep Advances
HCC
PKCδ
Biomarker
Tumor Marker
Early Detection
title Protein Kinase C Delta Is a Novel Biomarker for Hepatocellular Carcinoma
title_full Protein Kinase C Delta Is a Novel Biomarker for Hepatocellular Carcinoma
title_fullStr Protein Kinase C Delta Is a Novel Biomarker for Hepatocellular Carcinoma
title_full_unstemmed Protein Kinase C Delta Is a Novel Biomarker for Hepatocellular Carcinoma
title_short Protein Kinase C Delta Is a Novel Biomarker for Hepatocellular Carcinoma
title_sort protein kinase c delta is a novel biomarker for hepatocellular carcinoma
topic HCC
PKCδ
Biomarker
Tumor Marker
Early Detection
url http://www.sciencedirect.com/science/article/pii/S2772572322001340
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