Translational clinical feasibility of recent advances in liquid biopsy technology in effusion fluids: preliminary results

Introduction

Recent advancements in molecular profiling technologies based on liquid media (so-called liquid biopsy) have achieved a significant increase in detection sensitivity, enhancing our power of investigation for biofluids and suggesting their potential integration into pivotal diagnostic and predictive molecular analysis, such in non-small-cell lung cancer. Pre-analytical variables play a crucial role in the accuracy of analysis results. Evidence suggests that supernatant fluid obtained from cytological sample centrifugation is enriched with nucleic acids and less susceptible to nucleic acid degradation during processing compared to cytoblock samples. This study reports preliminary results from a recent workflow implementation of liquid biopsy in a routine molecular biology laboratory within the context of a validation study.

Methods

Eleven cytological samples of lung adenocarcinoma and corresponding cytoblock slides underwent a morphological analysis and review in terms of cellularity, cell integrity, necrosis/debris, and the presence of artifacts. Following NSG analysis of both the effusion fluid and cytoblock, data analysis and a comparison of the results were performed, focusing on concordance and the pre-analytical and analytical variables observed in the two groups.

Results

Molecular profiling led to the detection of an actionable alteration in all patients, with more robust results, evaluated in terms of variant allele frequency (VAF) in the supernatant group (53,3%) in comparison with the cytoblock group (26,49 %). This study resulted in a 100% concordance in molecular profiling between the cytoblock and supernatant analyses, with the latter showing higher yields in nucleic acid extraction, suggesting the possibility of achieving clinically useful results for running molecular profiling on biofluid materials.

Conclusions

Liquid biopsy technology has gained enough robustness to be a useful tool in routine analysis.

Biofluid applications in tumor molecular profiling is a promising field of exploration with outstanding potential in the case of insufficient cytologic material, contributing to improved patient management and thus avoiding repetitive procedures and optimizing the overall efficiency and cost-effectiveness of diagnostic practices.