MR features based on LI-RADS identify cytokeratin 19 status of hepatocellular carcinomas

Hu, Xueqin; Wang, Wentao; Yang, Li; Yang, Zhaoxia; Liang, He-Yue; Ding, Ying; Ji, Yuan; Zeng, Mengsu; Rao, Sheng-Xiang

doi:10.1016/j.ejrad.2019.01.036

Cited by 17 publications

(25 citation statements)

References 28 publications

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“…for prediction of CK19 expression was not high in our study, which was similar to the results of previous studies; 13,14 therefore, there remain barriers to its application in daily practice. We found that compared with the model based on traditional features evaluated by radiologists, the DLR model had significantly better performance in predicting CK19 in HCC.…”

Section: Discussionsupporting

confidence: 91%

“…We found that targetoid features in MRI, such as arterial rim enhancement and target sign on DWI/HBP, were closely related to CK19 in HCC, which was similar to the findings of Hu et al 14 Previous studies have indicated that arterial rim enhancement and target sign on DWI were important independent predictors for the diagnosis of intrahepatic cholangiocarcinoma (ICC), 25,26 which are related to the pathological morphology of peripheral hyperproliferation and central stromal fibrosis. 27 The formation of stromal fibrosis seemed to be more common in CK19-positive HCCs than in CK19-negative HCCs, which indicated the morphological characteristics of DPHCC could be between those of typical HCC and ICC.…”

Section: Discussionsupporting

confidence: 88%

“…10 Several studies have shown that imaging is closely related to the biological behavior and gene expression of HCC. 11,12 Some studies have evaluated the imaging findings related to CK19 expression in HCCs; 13,14 however, significant limitations in predicting CK19 using imaging findings remain. First, the analysis of image features is subjective and poor in terms of repeatability.…”

Section: Introductionmentioning

confidence: 99%

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Preoperative Prediction of Cytokeratin 19 Expression for Hepatocellular Carcinoma with Deep Learning Radiomics Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging

Chen¹,

Chen²,

Lin³

et al. 2021

JHC

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Cytokeratin 19 (CK19) expression is a proven independent prognostic predictor of hepatocellular carcinoma (HCC). This study aimed to develop and validate the performance of a deep learning radiomics (DLR) model for CK19 identification in HCC based on preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI). Patients and Methods: A total of 141 surgically confirmed HCCs with preoperative gadoxetic acid-enhanced MRI from two institutions were included. Prediction models were established based on hepatobiliary phase (HBP) images using a training set (n=102) and validated using time-independent (n=19) and external (n=20) test sets. A receiver operating characteristic curve was used to evaluate the performance for CK19 prediction. Recurrencefree survival (RFS) was also analyzed by incorporating the CK19 expression and other factors. Results: For predicting CK19 expression, the area under the curve (AUC) of the DLR model was 0.820 (95% confidence interval [CI]: 0.732-0.907, P<0.001) with sensitivity, specificity, accuracy of 0.800, 0.766, and 0.775, respectively, and reached 0.781 in the external test set. Combined with alpha fetoprotein, the AUC increased to 0.833 (95% CI: 0.753-0.912, P<0.001) and the sensitivity was 0.960. Intratumoral hemorrhage and peritumoral hypointensity on HBP were independent risk factors for HCC recurrence by multivariate analysis. Based on predicted CK19 expression and the independent risk factors, a nomogram was developed to predict RFS and achieved C-index of 0.707. Conclusion:This study successfully established and verified an optimal DLR model for preoperative prediction of CK19-positive HCCs based on gadoxetic acid-enhanced MRI. The prediction of CK19 expression in HCC using a non-invasive method can help inform preoperative planning.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Preoperative Prediction of Cytokeratin 19 Expression for Hepatocellular Carcinoma with Deep Learning Radiomics Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging

Chen¹,

Chen²,

Lin³

et al. 2021

JHC

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“…Choi et al 73 determined the preoperative magnetic resonance (MR) imaging characteristics of HCC potentially related to CK19 expression. Another study illustrated that MR features combining with elevated AFP were able to distinguish CK19-positive HCCs from CK19-negative HCC 74 . Therefore, application of these non-invasive detection methods will be conducive to monitor the CK19 expression status.…”

Section: The Detective and Therapeutic Strategy For Ck19 Positive Hccmentioning

confidence: 99%

CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype

Zhuo

Tan

et al. 2020

J. Cancer

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The heterogeneity of hepatocellular carcinoma (HCC) commonly leads to therapeutic failure of HCC. Cytokeratin 19 (CK19) is well acknowledged as a biliary/progenitor cell marker and a marker of tumor stem cell. CK19-positive HCCs demonstrate aggressive behaviors and poor outcomes which including worse overall survival and early tumor recurrence after hepatectomy and liver transplantation. CK19-positive HCCs are resistant to chemotherapies as well as local treatment. This subset of HCC is thought to derive from liver progenitor cells and can be induced by extracellular stimulation such as hypoxia. Besides being a stemness marker, CK19 plays an important role in promoting malignant property of HCC. The regulatory network associated with CK19 expression has been summarized that extracellular stimulations which transmit into cytoplasm through signal transduction pathways (TGF-β, MAKP/JNK and MEK-ERK1/2), further induce important nuclear transcriptional factors (SALL4, AP1, SP1) to activate CK19 promoter. Novel noncoding RNAs are also involved in the regulation of CK19 expression. TGFβR1 becomes a therapeutic target for CK19-positive HCC. In conclusion, CK19 can be a potential biomarker for predicting poor prognosis after surgical and adjuvant therapies. CK19-pisitive HCCs exhibit distinctive molecular profiling, should be diagnosed and treated as a separate subtype of HCCs.

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“…The expression of CK-19 is correlated with some clinicopathological features of tumor such as poor differentiation, metastasis, and early recurrence after tumor resection or radiofrequency ablation [108] . The arterial rim enhancement, targetoid appearance, non-peripheral "washout", and irregular tumor margins on gadoxetic acid-enhanced MRI are reported to be effective imaging markers for evaluating the CK-19 status of HCC [109][110][111][112] . Moreover, lower tumor-to-liver ADC and signal intensity ratios in HBP images may be helpful for predicting CK19-positive HCC with early recurrence [112] .…”

Section: Cytokeratin-19mentioning

confidence: 99%

Imaging biomarkers for predicting poor prognosis of hepatocellular carcinoma: a review

Zhang¹,

Huang²,

Chen³

et al. 2020

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Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high mortality rate. Heterogeneity is the main biological characteristic of HCC, which manifests through the different biological behaviors of each phenotype and ultimately, affects patient prognosis and treatment efficacy. Various aggressive biological behaviors are considered to be associated with the poor prognosis of HCC patients including poor differentiation, microvascular invasion, intracellular fat accumulation, invasive growth, bile duct invasion or tumor thrombosis, and tumor spread and metastasis, and have been reported as prognostic biomarkers. In addition, HCC results from multifactor synergistic damage, and various factors related to genetics, molecular pathology and immunohistochemistry such as β-catenin, Ki67, cytokeratin-19, and epithelial cell adhesion molecule have an impact on HCC differentiation and prognosis. This article is an overview of the biological behaviors that lead to poor prognosis of HCC, and the roles of morphological and quantitative noninvasive imaging biomarkers in the evaluation and prediction of these behaviors. Some common biomarkers related to genetics, molecular pathology and immunohistochemistry are also briefly summarized. It is hoped that this review will provide clinicians and radiologists with an update on the development of liver imaging, and provide directions for the combination of radiology, genetics, molecular pathology and histopathology to better predict the prognosis of HCC patients.

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MR features based on LI-RADS identify cytokeratin 19 status of hepatocellular carcinomas

Cited by 17 publications

References 28 publications

Preoperative Prediction of Cytokeratin 19 Expression for Hepatocellular Carcinoma with Deep Learning Radiomics Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging

Preoperative Prediction of Cytokeratin 19 Expression for Hepatocellular Carcinoma with Deep Learning Radiomics Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging

CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype

Imaging biomarkers for predicting poor prognosis of hepatocellular carcinoma: a review

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