Circulating tumor cells with stem-like phenotypes for diagnosis, prognosis and therapeutic response evaluation in hepatocellular carcinoma

Purpose: In present study, we assessed the clinical value of circulating tumor cells (CTCs) with stem-like phenotypes for diagnosis, prognosis and surveillance in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by an optimized QPCR-based detection platform. Experimental Design:Differing subsets of CTCs were investigated, and a multimarker diagnostic CTC panel was constructed in a multicenter-patient study with independent validation (total n=1006), including healthy individuals, patients with chronic hepatitis B infection (CHB), liver cirrhosis (LC), benign hepatic lesion (BHL) and HBV-related HCC, with area under the receiver operating characteristic curve (AUC-ROC) reflecting diagnostic accuracy. The role of CTC panel in treatment response surveillance and its prognostic significance were further investigated. Results: The AUC of CTC panel was 0.88 in training set [sensitivity=72·5%, specificity=95.0%, positive predictive value (PPV) =92.4, negative predictive value (NPV)=77.8] and 0.93 in validation set (sensitivity=82·1%; specificity=94.2%, PPV=89.9, NPV=89.3). This panel performed equally well in detecting early-stage and α-fetoprotein (AFP)-negative HCC, as well as differentiating HCC from CHB, LC and BHL. The CTC load was decreased significantly after tumor resection, and patients with persistently high CTC load showed a propensity of tumor recurrence after surgery. The prognostic significance of CTC panel in predicting tumor recurrence was further confirmed (training: HR=2.692, 95% CI, 1.617-4.483, P<0.001; validation: HR=3.127, 95% CI, 1.360-7.190, P=0.007). Conclusions: Our CTC panel showed high sensitivity and specificity in HCC diagnosis and could be a real-time parameter for risk prediction and treatment monitoring, enabling early decision-making to tailor effective antitumor strategies.

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