Preoperative prediction of cholangiocyte phenotype hepatocellular carcinoma on contrast-enhanced MRI and the prognostic implication after hepatectomy

Abstract

Abstract Background Hepatocellular carcinoma (HCC) expressing cytokeratin (CK) 7 or CK19 has a cholangiocyte phenotype that stimulates HCC proliferation, metastasis, and sorafenib therapy resistance This study aims to noninvasively predict cholangiocyte phenotype-positive HCC and assess its prognosis after hepatectomy. Methods Between January 2010 and May 2022, preoperative contrast-enhanced MRI was performed on consecutive patients who underwent hepatectomy and had pathologically confirmed solitary HCC. Two abdominal radiologists separately assessed the MRI features. A predictive model for cholangiocyte phenotype HCC was created using logistic regression analysis and five-fold cross-validation. A receiver operating characteristic curve was used to calculate the model performance. Kaplan–Meier and log-rank methods were used to evaluate survival outcomes. Results In total, 334 patients were included in this retrospective study. Four contrast-enhanced MRI features, including “rim arterial phase hyperenhancement” (OR = 5.9, 95% confidence interval [CI]: 2.9–12.0, 10 points), “nodule in nodule architecture” (OR = 3.5, 95% CI: 2.1–5.9, 7 points), “non-smooth tumor margin” (OR = 1.6, 95% CI: 0.8–2.9, 3 points), and “non-peripheral washout” (OR = 0.6, 95% CI: 0.3–1.0, − 3 points), were assigned to the cholangiocyte phenotype HCC prediction model. The area under the curves for the training and independent validation set were 0.76 and 0.73, respectively. Patients with model-predicted cholangiocyte phenotype HCC demonstrated lower rates of recurrence-free survival (RFS) and overall survival (OS) after hepatectomy, with an estimated median RFS and OS of 926 vs. 1565 days (p < 0.001) and 1504 vs. 2960 days (p < 0.001), respectively. Conclusions Contrast-enhanced MRI features can be used to predict cholangiocyte phenotype-positive HCC. Patients with pathologically confirmed or MRI model-predicted cholangiocyte phenotype HCC have a worse prognosis after hepatectomy. Critical relevance statement Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC and a worse prognosis following hepatectomy; these features may assist in predicting prognosis after surgery and improve personalized treatment decision-making. Key points • Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC. • A noninvasive cholangiocyte phenotype HCC predictive model was established based on MRI features. • Patients with cholangiocyte phenotype HCC demonstrated a worse prognosis following hepatic resection. Graphical Abstract

Keywords

• Hepatocellular carcinoma
• Magnetic resonance imaging
• Cytokeratin 7
• Cytokeratin 19
• Cholangiocyte phenotype