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...
Main Authors: | , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2023-01-01
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Series: | Gastro Hep Advances |
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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. |
first_indexed | 2024-04-11T07:09:22Z |
format | Article |
id | doaj.art-cf131429236646858d07c3fc33c2c03e |
institution | Directory Open Access Journal |
issn | 2772-5723 |
language | English |
last_indexed | 2024-04-11T07:09:22Z |
publishDate | 2023-01-01 |
publisher | Elsevier |
record_format | Article |
series | Gastro Hep Advances |
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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