Comparative Analysis of Circulating Tumor Cells, Clusters, and PD-L1 Expression in Paired
Peripheral and Portal Venous Blood with Solid Malignancies

Introduction

Circulating tumor cells (CTCs) are an established biomarker for prognostication, minimal residual cellular disease (MRCD), and treatment monitoring. Portal venous blood (PVB), which directly drains gastrointestinal and hepatobiliary tumors, may contain a higher CTC population than peripheral blood (PB) and could serve as a strong predictive biomarker for postoperative relapse in resected pancreatic cancer. This study evaluates CTC enumeration, CTC clusters, and PD-L1 expression in paired PB and PVB samples.

Methods

In this prospective observational study, paired PB and PVB samples were collected from 12 patients with hepatobiliary, pancreatic, colorectal, and gastric malignancies during interventional procedures. CTCs were enriched and identified using validated morphological and immunophenotypic criteria. PD-L1 expression and CTC clusters were evaluated by immunostaining. Detection rates, mean CTC counts, compartment concordance, and cancer-specific differences were analyzed descriptively.

Results

Eleven paired samples were evaluable. CTC positivity was observed in 90.9% (10/11) of PB samples and 81.8% (9/11) of PVB samples. Mean CTC counts were identical in both compartments (1.09). PD-L1-positive CTCs were more frequently detected in PB than PVB (45.5% vs. 18.2%), with corresponding mean counts of 0.45 and 0.18, respectively. CTC clusters were identified in 18.2% of cases in both compartments. Hepatocellular carcinoma and cholangiocarcinoma demonstrated high PB-PVB concordance, whereas pancreatic and rectal cancers showed compartment-specific discordance. Single CTCs predominated in both PB (72.7%) and PVB (63.6%).

Conclusion

Portal venous sampling is feasible and provides CTC detection rates comparable to peripheral blood. However, PB demonstrated greater detection of PD-L1-positive CTCs, suggesting compartment-specific biological differences. Combined assessment of PB and PVB may enhance liquid biopsy characterization, particularly in gastrointestinal malignancies. Larger prospective studies are warranted to define the clinical value of dual-compartment CTC profiling.