The prognostic potential of fragmented CK18 serum levels in HCC patients reflecting disease progression and overall hepatocyte damage
Copyright © 2022 Eguchi, Iwasa, Tamai, Yamada, Okuno, Shigefuku, Yoshikawa, Tempaku, Sakaguchi, Tanaka, Sugimoto, Kobayashi, Yamaguchi and Nakagawa..
Background: Fragmented cytokeratin 18 (fCK18) is released from damaged hepatocytes undergoing apoptosis and is recognized as a liver condition biomarker. We have developed a highly sensitive serum fCK18 CLEIA and reported that serum levels of this caspase-derived protein were significantly associated with hepatocyte ballooning, thus assisting in the accurate diagnosis of nonalcoholic steatohepatitis (NASH). We aim to investigate serum fCK18 levels in a variety of chronic liver diseases and to explore its potential as a prognostic marker of survival in hepatocellular carcinoma (HCC) patients.
Methods: Serum fCK18 levels were measured using a highly sensitive CLEIA in 497 chronic liver disease patients (297 outpatients and 200 hospitalized with HCC).
Results: In 497 chronic liver disease patients, serum fCK18 levels were significantly correlated with overall liver condition, including ALT, FIB-4 index and albumin-bilirubin (ALBI) score and were significantly increased in patients with HCC. In 200 HCC patients, serum fCK18 levels were significantly correlated with alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), and were significantly associated with HCC stage, whereas FIB-4 index and ALBI score were not changed based on HCC stage. The Survival group had significantly lower levels of serum fCK18, AFP, DCP, FIB-4 index and ALBI score. A ROC analysis yield area under the curve (AUC) value of 0.728 for serum fCK18 is a significantly high value when compared to AUC measurements for other factors. Notably, AUROC values for serum fCK18 levels were constant in the short- and long-term by time-dependent ROC analysis for the prediction of HCC patient survival. HCC patients with serum fCK18 measured at < 1.15 ng/mL, AFP < 7.7 ng/mL, DCP < 133 mAU/mL, ALBI score < -2.97 or FIB-4 index < 6.4 had significantly longer rates of survival when compared to patients with values exceeding these thresholds. Serum fCK18 (HR, 3.5; P < 0.0001), DCP (HR, 3.2; P < 0.0001) and Barcelona Clinic Liver Cancer (BCLC) (HR, 2.4; P = 0.001) values were independent predictors of patient survival. [Conclusion] Serum fCK18 levels reflect overall liver function, the level of liver fibrosis and the progression of HCC, and are a potential predictor of survival in HCC patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Frontiers in oncology - 12(2022) vom: 26., Seite 993705 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Eguchi, Akiko [VerfasserIn] |
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| Links: |
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| Themen: |
Cytokeratin 18 (CK18) |
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| Anmerkungen: |
Date Revised 12.09.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fonc.2022.993705 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345986458 |
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| 041 | |a eng | ||
| 100 | 1 | |a Eguchi, Akiko |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The prognostic potential of fragmented CK18 serum levels in HCC patients reflecting disease progression and overall hepatocyte damage |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Revised 12.09.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2022 Eguchi, Iwasa, Tamai, Yamada, Okuno, Shigefuku, Yoshikawa, Tempaku, Sakaguchi, Tanaka, Sugimoto, Kobayashi, Yamaguchi and Nakagawa. | ||
| 520 | |a Background: Fragmented cytokeratin 18 (fCK18) is released from damaged hepatocytes undergoing apoptosis and is recognized as a liver condition biomarker. We have developed a highly sensitive serum fCK18 CLEIA and reported that serum levels of this caspase-derived protein were significantly associated with hepatocyte ballooning, thus assisting in the accurate diagnosis of nonalcoholic steatohepatitis (NASH). We aim to investigate serum fCK18 levels in a variety of chronic liver diseases and to explore its potential as a prognostic marker of survival in hepatocellular carcinoma (HCC) patients | ||
| 520 | |a Methods: Serum fCK18 levels were measured using a highly sensitive CLEIA in 497 chronic liver disease patients (297 outpatients and 200 hospitalized with HCC) | ||
| 520 | |a Results: In 497 chronic liver disease patients, serum fCK18 levels were significantly correlated with overall liver condition, including ALT, FIB-4 index and albumin-bilirubin (ALBI) score and were significantly increased in patients with HCC. In 200 HCC patients, serum fCK18 levels were significantly correlated with alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), and were significantly associated with HCC stage, whereas FIB-4 index and ALBI score were not changed based on HCC stage. The Survival group had significantly lower levels of serum fCK18, AFP, DCP, FIB-4 index and ALBI score. A ROC analysis yield area under the curve (AUC) value of 0.728 for serum fCK18 is a significantly high value when compared to AUC measurements for other factors. Notably, AUROC values for serum fCK18 levels were constant in the short- and long-term by time-dependent ROC analysis for the prediction of HCC patient survival. HCC patients with serum fCK18 measured at < 1.15 ng/mL, AFP < 7.7 ng/mL, DCP < 133 mAU/mL, ALBI score < -2.97 or FIB-4 index < 6.4 had significantly longer rates of survival when compared to patients with values exceeding these thresholds. Serum fCK18 (HR, 3.5; P < 0.0001), DCP (HR, 3.2; P < 0.0001) and Barcelona Clinic Liver Cancer (BCLC) (HR, 2.4; P = 0.001) values were independent predictors of patient survival. [Conclusion] Serum fCK18 levels reflect overall liver function, the level of liver fibrosis and the progression of HCC, and are a potential predictor of survival in HCC patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a cytokeratin 18 (CK18) | |
| 650 | 4 | |a fCK18 | |
| 650 | 4 | |a fragmented cytokeratin 18 | |
| 650 | 4 | |a hepatocellular carcinoma (HCC) | |
| 650 | 4 | |a liver cirrhosis | |
| 650 | 4 | |a mortality | |
| 650 | 4 | |a prognostic factor | |
| 700 | 1 | |a Iwasa, Motoh |e verfasserin |4 aut | |
| 700 | 1 | |a Tamai, Yasuyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Yamada, Minori |e verfasserin |4 aut | |
| 700 | 1 | |a Okuno, Koji |e verfasserin |4 aut | |
| 700 | 1 | |a Shigefuku, Ryuta |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshikawa, Kyoko |e verfasserin |4 aut | |
| 700 | 1 | |a Tempaku, Mina |e verfasserin |4 aut | |
| 700 | 1 | |a Sakaguchi, Koji |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Hideaki |e verfasserin |4 aut | |
| 700 | 1 | |a Sugimoto, Kazushi |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Yoshinao |e verfasserin |4 aut | |
| 700 | 1 | |a Yamaguchi, Tetsuji |e verfasserin |4 aut | |
| 700 | 1 | |a Nakagawa, Hayato |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:12 |g year:2022 |g day:26 |g pages:993705 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fonc.2022.993705 |3 Volltext |
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