Skip to main content
Erschienen in: European Radiology 5/2020

30.01.2020 | Imaging Informatics and Artificial Intelligence

A radiomics-based biomarker for cytokeratin 19 status of hepatocellular carcinoma with gadoxetic acid–enhanced MRI

verfasst von: Wentao Wang, Dongsheng Gu, Jingwei Wei, Ying Ding, Li Yang, Kai Zhu, Rongkui Luo, Sheng-Xiang Rao, Jie Tian, Mengsu Zeng

Erschienen in: European Radiology | Ausgabe 5/2020

Einloggen, um Zugang zu erhalten

Abstract

Objectives

We aimed to develop a radiomics-based model derived from gadoxetic acid–enhanced MR images to preoperatively identify cytokeratin (CK) 19 status of hepatocellular carcinoma (HCC).

Methods

A cohort of 227 patients with single HCC was classified into a training set (n = 159) and a time-independent validated set (n = 68). A total of 647 radiomic features were extracted from multi-sequence MR images. The least absolute shrinkage and selection operator regression and decision tree methods were utilized for feature selection and radiomics signature construction. A multivariable logistic regression model incorporating clinico-radiological features and the fusion radiomics signature was built for prediction of CK19 status by evaluating area under curve (AUC).

Results

In the whole cohort, 57 patients were CK19 positive and 170 patients were CK19 negative. By combining 11 and 6 radiomic features extracted in arterial phase and hepatobiliary phase images, respectively, a fusion radiomics signature achieved AUCs of 0.951 and 0.822 in training and validation datasets. The final combined model integrated a-fetoprotein levels, arterial rim enhancement pattern, irregular tumor margin, and the fusion radiomics signature, with a sensitivity of 0.818 and specificity of 0.974 in the training cohort and that of 0.769 and 0.818 in the validated cohort. The nomogram based on the combined model showed satisfactory prediction performance in training (C-index 0.959) and validation (C-index 0.846) dataset.

Conclusions

The combined model based on a fusion radiomics signature derived from arterial and hepatobiliary phase images of gadoxetic acid–enhanced MRI can be a reliable biomarker for CK19 status of HCC.

Key Points

Arterial rim enhancement pattern and irregular tumor margin on hepatobiliary phase on gadoxetic acid–enhanced MRI can be useful for evaluating CK19 status of HCC.
A radiomics-based model performed better than the clinico-radiological model both in training and validation datasets for predicting CK19 status of HCC.
The nomogram based on the fusion radiomics signature can be easily used for CK19 stratification of HCC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917
2.
Zurück zum Zitat Forner A, Reig M, Bruix J (2010) Hepatocellular carcinoma. Lancet 391:1301–1314CrossRef Forner A, Reig M, Bruix J (2010) Hepatocellular carcinoma. Lancet 391:1301–1314CrossRef
3.
Zurück zum Zitat de Lope CR, Tremosini S, Forner A, Reig M, Bruix J (2012) Management of HCC. J Hepatol 56(Suppl 1):S75–S87CrossRef de Lope CR, Tremosini S, Forner A, Reig M, Bruix J (2012) Management of HCC. J Hepatol 56(Suppl 1):S75–S87CrossRef
4.
Zurück zum Zitat Forner A, Reig ME, de Lope CR, Bruix J (2010) Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis 30:61–74CrossRef Forner A, Reig ME, de Lope CR, Bruix J (2010) Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis 30:61–74CrossRef
5.
Zurück zum Zitat Mishra L, Banker T, Murray J et al (2009) Liver stem cells and hepatocellular carcinoma. Hepatology 49:318–329CrossRef Mishra L, Banker T, Murray J et al (2009) Liver stem cells and hepatocellular carcinoma. Hepatology 49:318–329CrossRef
6.
Zurück zum Zitat Hoshida Y, Nijman SM, Kobayashi M et al (2009) Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 69:7385–7392CrossRef Hoshida Y, Nijman SM, Kobayashi M et al (2009) Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 69:7385–7392CrossRef
7.
Zurück zum Zitat Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24CrossRef Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24CrossRef
8.
Zurück zum Zitat Durnez A, Verslype C, Nevens F et al (2006) The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology 49:138–151CrossRef Durnez A, Verslype C, Nevens F et al (2006) The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology 49:138–151CrossRef
9.
Zurück zum Zitat Kim H, Choi GH, Na DC et al (2011) Human hepatocellular carcinomas with “Stemness”-related marker expression: keratin 19 expression and a poor prognosis. Hepatology 54:1707–1717CrossRef Kim H, Choi GH, Na DC et al (2011) Human hepatocellular carcinomas with “Stemness”-related marker expression: keratin 19 expression and a poor prognosis. Hepatology 54:1707–1717CrossRef
10.
Zurück zum Zitat Roncalli M, Park YN, Di Tommaso L (2010) Histopathological classification of hepatocellular carcinoma. Dig Liver Dis 42:S228–S234CrossRef Roncalli M, Park YN, Di Tommaso L (2010) Histopathological classification of hepatocellular carcinoma. Dig Liver Dis 42:S228–S234CrossRef
11.
Zurück zum Zitat Lee CW, Kuo WL, Yu MC et al (2013) The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection. World J Surg Oncol 11:136CrossRef Lee CW, Kuo WL, Yu MC et al (2013) The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection. World J Surg Oncol 11:136CrossRef
12.
Zurück zum Zitat Zhuang PY, Zhang JB, Zhu XD et al (2008) Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor. Cancer 112:2740–2748CrossRef Zhuang PY, Zhang JB, Zhu XD et al (2008) Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor. Cancer 112:2740–2748CrossRef
13.
Zurück zum Zitat Fatourou E, Koskinas J, Karandrea D et al (2015) Keratin 19 protein expression is an independent predictor of survival in human hepatocellular carcinoma. Eur J Gastroenterol Hepatol 27:1094–1102CrossRef Fatourou E, Koskinas J, Karandrea D et al (2015) Keratin 19 protein expression is an independent predictor of survival in human hepatocellular carcinoma. Eur J Gastroenterol Hepatol 27:1094–1102CrossRef
14.
Zurück zum Zitat Lee SH, Lee JS, Na GH, You YK, Kim DG (2017) Immunohistochemical markers for hepatocellular carcinoma prognosis after liver resection and liver transplantation. Clin Transplant 31 Lee SH, Lee JS, Na GH, You YK, Kim DG (2017) Immunohistochemical markers for hepatocellular carcinoma prognosis after liver resection and liver transplantation. Clin Transplant 31
15.
Zurück zum Zitat Kawai T, Yasuchika K, Ishii T et al (2015) Keratin 19, a cancer stem cell marker in human hepatocellular carcinoma. Clin Cancer Res 21:3081–3091CrossRef Kawai T, Yasuchika K, Ishii T et al (2015) Keratin 19, a cancer stem cell marker in human hepatocellular carcinoma. Clin Cancer Res 21:3081–3091CrossRef
16.
Zurück zum Zitat Katoh H, Ojima H, Kokubu A et al (2007) Genetically distinct and clinically relevant classification of hepatocellular carcinoma: putative therapeutic targets. Gastroenterology 133:1475–1486CrossRef Katoh H, Ojima H, Kokubu A et al (2007) Genetically distinct and clinically relevant classification of hepatocellular carcinoma: putative therapeutic targets. Gastroenterology 133:1475–1486CrossRef
17.
Zurück zum Zitat Segal E, Sirlin CB, Ooi C et al (2007) Decoding global gene expression programs in liver cancer by noninvasive imaging. Nat Biotechnol 25:675–680CrossRef Segal E, Sirlin CB, Ooi C et al (2007) Decoding global gene expression programs in liver cancer by noninvasive imaging. Nat Biotechnol 25:675–680CrossRef
18.
Zurück zum Zitat Rutman AM, Kuo MD (2009) Radiogenomics: creating a link between molecular diagnostics and diagnostic imaging. Eur J Radiol 70:232–241CrossRef Rutman AM, Kuo MD (2009) Radiogenomics: creating a link between molecular diagnostics and diagnostic imaging. Eur J Radiol 70:232–241CrossRef
19.
Zurück zum Zitat Lambin P, Rios-Velazquez E, Leijenaar R et al (2012) Radiomics: extracting more information from medical images using advanced feature analysis. Eur J Cancer 48:441–446CrossRef Lambin P, Rios-Velazquez E, Leijenaar R et al (2012) Radiomics: extracting more information from medical images using advanced feature analysis. Eur J Cancer 48:441–446CrossRef
20.
Zurück zum Zitat Ma X, Wei J, Gu D et al (2019) Preoperative radiomics nomogram for microvascular invasion prediction in hepatocellular carcinoma using contrast-enhanced CT. Eur Radiol 29:3595–3605CrossRef Ma X, Wei J, Gu D et al (2019) Preoperative radiomics nomogram for microvascular invasion prediction in hepatocellular carcinoma using contrast-enhanced CT. Eur Radiol 29:3595–3605CrossRef
21.
Zurück zum Zitat Chen S, Feng S, Wei J et al (2019) Pretreatment prediction of immunoscore in hepatocellular cancer: a radiomics-based clinical model based on Gd-EOB-DTPA-enhanced MRI imaging. Eur Radiol 29:4177–4187CrossRef Chen S, Feng S, Wei J et al (2019) Pretreatment prediction of immunoscore in hepatocellular cancer: a radiomics-based clinical model based on Gd-EOB-DTPA-enhanced MRI imaging. Eur Radiol 29:4177–4187CrossRef
22.
Zurück zum Zitat Choi SY, Kim SH, Park CK et al (2018) Imaging features of gadoxetic acid-enhanced and diffusion-weighted MR imaging for identifying cytokeratin 19-positive hepatocellular carcinoma: a retrospective observational study. Radiology 286:897–908CrossRef Choi SY, Kim SH, Park CK et al (2018) Imaging features of gadoxetic acid-enhanced and diffusion-weighted MR imaging for identifying cytokeratin 19-positive hepatocellular carcinoma: a retrospective observational study. Radiology 286:897–908CrossRef
23.
Zurück zum Zitat Jeong HT, Kim MJ, Kim YE, Park YN, Choi GH, Choi JS (2012) MRI features of hepatocellular carcinoma expressing progenitor cell markers. Liver Int 32:430–440PubMed Jeong HT, Kim MJ, Kim YE, Park YN, Choi GH, Choi JS (2012) MRI features of hepatocellular carcinoma expressing progenitor cell markers. Liver Int 32:430–440PubMed
24.
Zurück zum Zitat Hectors SJ, Wagner M, Bane O et al (2017) Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging. Sci Rep 7:2452CrossRef Hectors SJ, Wagner M, Bane O et al (2017) Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging. Sci Rep 7:2452CrossRef
25.
Zurück zum Zitat Cong WM, Bu H, Chen J et al (2016) Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update. World J Gastroenterol 22:9279–9287 Cong WM, Bu H, Chen J et al (2016) Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update. World J Gastroenterol 22:9279–9287
26.
Zurück zum Zitat Gao Q, Qiu SJ, Fan J et al (2007) Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol 25:2586–2593CrossRef Gao Q, Qiu SJ, Fan J et al (2007) Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol 25:2586–2593CrossRef
27.
Zurück zum Zitat Yang XR, Xu Y, Shi GM et al (2008) Cytokeratin 10 and cytokeratin 19: predictive markers for poor prognosis in hepatocellular carcinoma patients after curative resection. Clin Cancer Res 14:3850–3859CrossRef Yang XR, Xu Y, Shi GM et al (2008) Cytokeratin 10 and cytokeratin 19: predictive markers for poor prognosis in hepatocellular carcinoma patients after curative resection. Clin Cancer Res 14:3850–3859CrossRef
28.
Zurück zum Zitat Van Griethuysen JJM, Fedorov A, Parmar C et al (2017) Computational radiomics system to decode the radiographic phenotype. Cancer Res 77:e104–e107CrossRef Van Griethuysen JJM, Fedorov A, Parmar C et al (2017) Computational radiomics system to decode the radiographic phenotype. Cancer Res 77:e104–e107CrossRef
29.
Zurück zum Zitat Leijenaar RTH, Carvalho S, Velazquez ER et al (2013) Stability of FDG-PET radiomics features: an integrated analysis of test-retest and inter-observer variability. Acta Oncol 52:1391–1397CrossRef Leijenaar RTH, Carvalho S, Velazquez ER et al (2013) Stability of FDG-PET radiomics features: an integrated analysis of test-retest and inter-observer variability. Acta Oncol 52:1391–1397CrossRef
30.
Zurück zum Zitat Tibshirani R (1997) The lasso method for variable selection in the Cox model. Stat Med 16:385–395CrossRef Tibshirani R (1997) The lasso method for variable selection in the Cox model. Stat Med 16:385–395CrossRef
31.
Zurück zum Zitat Kaminski B, Jakubczyk M, Szufel P (2018) A framework for sensitivity analysis of decision trees. Cent Eur J Oper Res 26:135–159CrossRef Kaminski B, Jakubczyk M, Szufel P (2018) A framework for sensitivity analysis of decision trees. Cent Eur J Oper Res 26:135–159CrossRef
32.
Zurück zum Zitat Taouli B, Hoshida Y, Kakite S et al (2017) Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma: preliminary results. Eur Radiol 27:4472–4481CrossRef Taouli B, Hoshida Y, Kakite S et al (2017) Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma: preliminary results. Eur Radiol 27:4472–4481CrossRef
33.
Zurück zum Zitat Boonzaier NR, Piccirillo SG, Watts C, Price SJ (2015) Assessing and monitoring intratumor heterogeneity in glioblastoma: how far has multimodal imaging come? CNS Oncol 4:399–410CrossRef Boonzaier NR, Piccirillo SG, Watts C, Price SJ (2015) Assessing and monitoring intratumor heterogeneity in glioblastoma: how far has multimodal imaging come? CNS Oncol 4:399–410CrossRef
34.
Zurück zum Zitat Davnall F, Yip CS, Ljungqvist G et al (2012) Assessment of tumor heterogeneity: an emerging imaging tool for clinical practice? Insights Imaging 3:573–589CrossRef Davnall F, Yip CS, Ljungqvist G et al (2012) Assessment of tumor heterogeneity: an emerging imaging tool for clinical practice? Insights Imaging 3:573–589CrossRef
35.
Zurück zum Zitat Kumar V, Gu Y, Basu S et al (2012) Radiomics: the process and the challenges. Magn Reson Imaging 30:1234–1248CrossRef Kumar V, Gu Y, Basu S et al (2012) Radiomics: the process and the challenges. Magn Reson Imaging 30:1234–1248CrossRef
36.
Zurück zum Zitat Yamashita T, Forgues M, Wang W et al (2008) EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res 68:1451–1461CrossRef Yamashita T, Forgues M, Wang W et al (2008) EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res 68:1451–1461CrossRef
37.
Zurück zum Zitat Kim H, Park YN (2014) Hepatocellular carcinomas expressing ‘stemness’-related markers: clinicopathological characteristics. Dig Dis 32:778–785CrossRef Kim H, Park YN (2014) Hepatocellular carcinomas expressing ‘stemness’-related markers: clinicopathological characteristics. Dig Dis 32:778–785CrossRef
38.
Zurück zum Zitat Lee Y, Park H, Lee H et al (2018) The clinicopathological and prognostic significance of the gross classification of hepatocellular carcinoma. J Pathol Transl Med 52:85–92CrossRef Lee Y, Park H, Lee H et al (2018) The clinicopathological and prognostic significance of the gross classification of hepatocellular carcinoma. J Pathol Transl Med 52:85–92CrossRef
39.
Zurück zum Zitat Chiba T, Kamiya A, Yokosuka O, Iwama A (2009) Cancer stem cells in hepatocellular carcinoma: recent progress and perspective. Cancer Lett 286:145–153CrossRef Chiba T, Kamiya A, Yokosuka O, Iwama A (2009) Cancer stem cells in hepatocellular carcinoma: recent progress and perspective. Cancer Lett 286:145–153CrossRef
40.
Zurück zum Zitat Rhee H, An C, Kim H, Yoo JE, Park YN, Kim M (2018) Hepatocellular carcinoma with irregular rim-like arterial phase hyperenhancement: more aggressive pathologic features. Liver Cancer:1–17 Rhee H, An C, Kim H, Yoo JE, Park YN, Kim M (2018) Hepatocellular carcinoma with irregular rim-like arterial phase hyperenhancement: more aggressive pathologic features. Liver Cancer:1–17
Metadaten
Titel
A radiomics-based biomarker for cytokeratin 19 status of hepatocellular carcinoma with gadoxetic acid–enhanced MRI
verfasst von
Wentao Wang
Dongsheng Gu
Jingwei Wei
Ying Ding
Li Yang
Kai Zhu
Rongkui Luo
Sheng-Xiang Rao
Jie Tian
Mengsu Zeng
Publikationsdatum
30.01.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
European Radiology / Ausgabe 5/2020
Print ISSN: 0938-7994
Elektronische ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-019-06585-y

Weitere Artikel der Ausgabe 5/2020

European Radiology 5/2020 Zur Ausgabe

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

S3-Leitlinie zu Pankreaskrebs aktualisiert

23.04.2024 Pankreaskarzinom Nachrichten

Die Empfehlungen zur Therapie des Pankreaskarzinoms wurden um zwei Off-Label-Anwendungen erweitert. Und auch im Bereich der Früherkennung gibt es Aktualisierungen.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.