Circulating Tumor Cells with Stem-Like Phenotypes for Diagnosis, Prognosis, and Therapeutic Response Evaluation in Hepatocellular Carcinoma

Abstract

In the present study, we assessed the clinical value of circulating tumor cells (CTC) 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. Differing subsets of CTCs were investigated, and a multimarker diagnostic CTC panel was constructed in a multicenter patient study with independent validation (total = 1,006), including healthy individuals and 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 the CTC panel in treatment response surveillance and its prognostic significance were further investigated. The AUC of the CTC panel was 0.88 in the training set [sensitivity = 72.5%, specificity = 95.0%, positive predictive value (PPV) = 92.4, negative predictive value (NPV) = 77.8] and 0.93 in the 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-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 the CTC panel in predicting tumor recurrence was further confirmed [training: HR = 2.692; 95% confidence interval (CI), 1.617-4.483; < 0.001; and validation: HR = 3.127; 95% CI, 1.360-7.190; = 0.007]. 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. .

Postoperative circulating tumor cells: An early predictor of extrahepatic metastases in patients with hepatocellular carcinoma undergoing curative surgical resection

“…Similarly, Schulze et al demonstrated that CTCs were statistically significantly associated with deteriorated survival in patients with intermediate or advanced HCC 26 . We also found that the dynamic changes in the CTC count reflected the treatment efficacy of liver resection for patients with HCC 27,28 . However, to our knowledge, the predictive impact of CTC on EHM in patients with HCC who are undergoing curative surgical resection remains unclear.…”

<p>Dynamic Changes in Serum Markers and Their Utility in the Early Diagnosis of All Stages of Hepatitis B-Associated Hepatocellular Carcinoma</p>

“…At present, the application of CTCs in liver cancer is basically limited to staging, prognosis 40 and therapeutic response evaluation. [41][42][43][44] Protein markers are classic tumuor markers with known stability. In general, good protein markers have considerable advantages in sensitivity and specificity.…”

Detection of circulating tumor cells in hepatocellular carcinoma: applications in diagnosis, prognosis prediction and personalized treatment

“…CTCs in patients with HCC are a highly heterogeneous population; currently, there are no widely accepted antigens specifically targeting HCC CTCs [27,63] . Although CellSearch TM system is commonly used in CTC detection, it is reported that the EpCAM-based CTC-sorting strategy could only identify approximately 10%-35% of the total amount of tumor cells in blood due to the EMT process and heterogeneous CTC molecular phenotypes [64,65] .…”