No abstract

Since the mortality of lung cancer patients remains very high, development of prognostic methods essential for efficient therapy is an immediate task. This study was designed to assess the value of circulating DNA (cirDNA) in blood as a prognostic marker in patients with non-small cell lung cancer. The average concentration of cirDNA in plasma was shown to be similar in healthy donors and lung cancer patients. However, the concentration of cell-surface-bound circulating DNA (csb-cirDNA) in lung cancer patients is significantly lower than that found in healthy donors (P < 0.0001) and correlates with a poor prognosis of tumor disease. Quantification of the cell-surface-bound DNA in blood of untreated patients allows persons with a poor prognosis of tumor disease to be detected with 94% sensitivity and 50% specificity.

Dynamic change of trends for miR-19b and miR-125b expression levels and miR-125b/miR-19b ratio in the blood plasma have shown a potentiality to discriminate types of response to antitumor therapy in lung cancer patients. Further in-depth investigation is needed to establish a direct link the miRNAs expression levels in blood plasma with therapy response and patient's survival.

Alterations in the patterns of DNA methylation are among the earliest and most common events in tumorigenesis. Epigenetic changes were shown to be detectable in DNA, circulating in blood (cirDNA) of cancer patients, indicating the resources to create the minimally invasive diagnostic tests based on tumor-specific DNA markers. RARβ2 methylation level was significantly increased in plasma cirDNA and cell surface-bound cirDNA (csb-cirDNA) from patients with non-small cell lung cancer compared with healthy individuals (7620 and 1083 copies/ml in the csb fractions, 3589 and 1068 copies/ml in the blood plasma; P=0.003 and 0.001). The cell-bound-to-cell-free RARβ2 methylation ratio was found to be elevated in patients with non-small cell lung cancer compared with control (2.12 and 1.01, respectively; P=0.023). RARβ2 methylation level in csb-cirDNA and plasma cirDNA was higher in stage III patients compared with stage I-II patients (P=0.02 and 0.03). In the subgroup of patients with squamous cell carcinoma, RARβ2 methylation level in the cbs-cirDNA was higher compared with patients with adenocarcinoma (P=0.04). Epigenetic alterations of tumor suppressor gene RARβ2 in the total cirDNA (plasma cirDNA and csb-cirDNA) were found to be associated with lung cancer progression. The data obtained indicate that cirDNA-based testing provides a valuable source for subsequent verification of methylated DNA markers for lung cancer diagnostics and prognosis.

The significance of the role of human papillomavirus (HPV) in the development of lung cancer remains an open question. The data from the literature do not provide conclusive evidence of HPV being involved in the pathogenesis of lung cancer. The aim of this work was to detect the presence of HPV infections with a high carcinogenic risk in patients with non-small cell lung cancer (NSCLC). Materials and methods: the study involved 274 patients with stage IIA–IIIB non-small cell lung cancer. We analyzed normal and tumor tissues as well as blood from each patient. DNA was extracted from patients’ specimens, and HPV detection and genotyping was carried out using commercially available kits by PCR. Results: HPV was detected in 12.7% of the patients (35/274 of all cases). We detected nine different types of human papillomavirus in the patients, namely, types 16, 18, 31, 35, 45, 51, 52, 56, and 59. The HPV-positive samples had a clinically insignificant viral load and were predominantly integrated. The relationship between the presence of HPV and its virological parameters and the clinical and pathological parameters of the patients was established. A metastatic-free survival analysis showed that all patients with HPV in the tumor tissue had a higher 5-year survival rate (94%) compared with the HPV-negative patients (78%). The result was not statistically significant (p = 0.08). Conclusions: data showing a 12.7% human papillomavirus representation among patients with non-small cell lung cancer were obtained. The presence/absence of a viral component in patients with lung cancer was a clinically significant parameter. HPV types 16, 18, and 56, which are the most oncogenic, were most often detected.