Lung cancer diagnosis with liquid biopsy of peripheral blood cells

A change in DNA damage sensitivity is a common feature amongst cancer patients. Liquid biopsy of blood samples can be used to distinguish early- and advanced-stage lung cancer patients from healthy donors.

Liquid biopsy using peripheral blood sampling is a minimally invasive approach that permits investigating cancers in a cost-effective and patient-friendly manner. Several liquid biopsy assays, mostly targeting circulating tumour cells or ctDNA, have been introduced into clinical practice but their applicability for early-stage disease is limited due to low levels of circulating markers in the blood. On the other hand, peripheral blood mononuclear cells (PBMCs) are present in large quantities in the blood and have been extensively used in biomonitoring studies. German and Swiss researchers evaluated the sensitivity of DNA damage sensitivity in PBMCs to detect early-stage lung cancer in a cost-effective and patient-friendly manner.

Participants presenting with either a diagnosis of lung cancer (n=26) or healthy donors (n=31) were enrolled in this observational study. All lung cancer subtypes and clinical stages were included (50% adenocarcinoma, 23% squamous, 15% small cell lung cancer, 4% non-small cell lung cancer, 8% neuroendocrine tumours; 12% stage I, 19% stage II, 34% stage III, 35% stage IV). Blood samples were collected before any kind of treatment through venepuncture. Extracted PBMCs were tested using the 4D Lifetest^TM assay, an algorithm-based, high-performance electrophoresis approach, which measures the level of DNA damage at the single-cell level. The level of DNA damage was assessed both at the baseline level and after minimal induction of DNA damage by UV, and DNA damage sensitivity was calculated. Dr Andreas Thomsen (University of Freiburg, Germany) presented the results [1].

Evaluation of DNA damage sensitivity comparing non-cancer with early-stage lung cancer (stage I–II) samples resulted in >95% sensitivity and 97% specificity. For advanced disease (stage III–IV), a sensitivity of 94% was observed. Across all stages, the sensitivity reached >95%. The assay did not significantly discriminate between lung cancer subtypes, thus serving as a broad test for lung cancer diagnosis.

Based on these results, Dr Thomson concluded that a change in DNA damage sensitivity in PBMCs is a common feature amongst lung cancer patients and can be used to distinguish early- and advanced-stage lung cancer from healthy donor samples. Therefore, this assay has the potential to overcome the limitations of conventional liquid biopsy approaches for early-stage cancer detection.

1. Thomsen AR, et al. Early-stage diagnosis of lung cancer with liquid biopsy test based on peripheral blood cells. Abstract 184P. ELCC 2022 Virtual Meeting, 30 March–02 April.

 

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Posted on 25 May, 2022