Abstract. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are routinely used to treat non-small cell lung cancer (NSCLC) in patients with common activating mutations of the EGFR gene. The aim of the study was to compare the efficacies of EGFR-TKIs in patients with common (exon 19 deletions and exon 21 p.Leu858Arg) and rare EGFR mutations. A retrospective analysis of 180 NSCLC patients with common (n=167) and rare (n=13) EGFR mutations treated with erlotinib (n=98), gefitinib (n=66) and afatinib (n=16) was performed. EGFR mutations were determined using RT-PCR and the EntroGen EGFR Mutations Analysis kit. Partial and complete response (PR and CR), progression-free survival (PFS), and overall survival (OS) were analyzed. Demographic and clinical factors had no impact on PFS or OS in patients treated with EGFR-TKIs. Erlotinib, gefitinib, and afatinib showed similar efficacies based on treatment response, median PFS, and OS. The type of EGFR mutation had no impact on median OS; however, median PFS was significantly longer in patients with the exon 19 deletion compared to patients with the exon 21 p.Leu858Arg substitution and rare EGFR gene mutations (P=0.013). Patients with common EGFR mutations showed significantly longer median PFS than those with rare EGFR mutations (10 vs. 5 months; P=0.009). Erlotinib, gefitinib, and afatinib show similar efficacies in NSCLC patients with both common and rare EGFR mutations. When undergoing EGFR-TKI treatment, patients with rare EGFR mutations showed similar OS but poorer PFS. Further investigation into the associations between particular rare EGFR mutations and EGFR-TKIs treatment outcomes is required.
Currently, there are no sensitive diagnostic tests that could allow early detection of lung cancer. Among some cancer patients, epigenetic changes in the nature of methylation of different gene promoter regions are observed, which affect expression of suppressor genes such as septin 9 (SEPT9). Due to the ability of detecting these changes in free circulating DNA in peripheral blood, such genes may become ideal markers in early and noninvasive diagnostics of cancer. Methylation of SEPT9 promoter region in plasma DNA is observed frequently in colorectal cancer patients. The aim of the study was to define the frequency of SEPT9 promoter methylation in lung cancer patients and evaluation of usefulness of this marker in early diagnostic of lung cancer. Plasma samples were obtained from 70 untreated patients with different lung cancer pathological diagnosis and disease stage and from 100 healthy individuals. DNA was isolated from peripheral blood plasma and was then subjected to bisulfitation, purification and elution using Abbott mSEPT9 Detection Kit. Methylation level was assessed by real-time PCR with the use of specific SEPT9 promoter methylation probe. Each sample was assayed in the presence of positive and negative control. SEPT9 promoter methylation was detected in 31 (44.3 % of the whole studied group) of lung cancer patients finding the result positive when methylation was detected in 1 out of 3 repetitions of each test sample determinations. The marker was present in patients with different pathological diagnosis and disease stage. Analysis of SEPT9 promoter region methylation may be useful in early diagnosis of lung cancer.
Aberrant expression of microRNAs (miRNAs) in cancer patients compared to healthy people as well as possibility of detection of these molecules in blood samples make them potential biomarkers of various cancers. In the present study, we investigated the potential role of four miRNAs as lung cancer (LC) biomarkers: miRNA-448, 506, 4316, and 4478. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) technique, we assessed expression of studied miRNAs in plasma samples of 90 lung cancer patients and 85 healthy individuals. Receiver operating curves (ROC) with area under the curve (AUC) were used to assess accuracy of studied miRNAs for distinguishing LC patients from healthy individuals. The miRNA-448 and 4478 were significantly overexpressed in lung cancer patients compared to healthy people and these two molecules were qualified for further analysis. Combination ROC analysis of both biomarkers reached 90 % of sensitivity and 76.3 % of specificity (AUC = 0.896) for distinguishing operable (stage IA-IIB) non-small cell lung cancer (NSCLC) patients from healthy subjects. Our results suggest that the examination of miRNAs could be considered as potential lung cancer, non-invasive biomarkers.
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