Registration Number
0224U033204,
(0123U102755)
, R & D reports
Title
The role of the DNA repair system in the pathogenesis and immunogenicity of lung cancer
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Імуногістохімічне та молекулярно-генетичне дослідження НДКРЛ Аналіз отриманих даних
Head
Moskalenko Roman A., Доктор медичних наук
Registration Date
20-12-2024
Organization
Sumy State University
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The study aims to assess the relationship between DNA repair defects and the molecular profile and characteristics of the tumor immune microenvironment in NSCLC to determine these parameters' prognostic and predictive value
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For the first time, using modern next-generation sequencing (NGS) technologies, the frequency of various types of genetic alterations in NSCLC in the Ukrainian population was determined, and the specificity of the tumour immune microenvironment in NSCLC was assessed, taking into account the histological type of the tumour and its molecular landscape. Immunohistochemical study of NSCLC samples for the expression of tumour microenvironment markers (CD68, CD163, FOXP3 and PD-L1) was performed on 117 samples of patients with NSCLC, including 95 adenocarcinomas and 22 squamous cell carcinomas. It was found that according to the level of expression of macrophages of the M1 and M2 immunophenotypes, tumour samples can be divided into several profiles, and the study of the types of these is ongoing. Comparison of Foxp3 expression in the tumour microenvironment of squamous cell carcinoma and adenocarcinoma showed a significant difference between these indicators (p<0.05). This means that against the background of immunotherapy, the presence of immunosuppressive CD4+ T-cells (FOXP3+ cells) is higher in the tissue of squamous cell lung cancer than in adenocarcinoma. This may be due to the different effectiveness of immunotherapy in different histological forms of NSCLC.
Among 117 NSCLC samples, 51 cases (43.6%) had negative PD-L1 expression. In 66 cases, positive PD-L1 expression was recorded, among which 45 carcinomas (38.5%) had PD-L1+low status and 21 (17.9%) - PD-L1+high.
Genetic abnormalities were detected mainly in lung adenocarcinoma (p<0.001). When assessing the frequency of genetic alterations in NSCLC, EGFR mutations were detected in 17 patients (14.5%), ALK rearrangements in 8 cases (6.8%), KRAS in 23 (19.7%), ROS1 in 2 (1.7%), MET in 3 (2.6%), BRAF in 3 (2.6%) cases, and also in 23 cases (19.7%) alterations in other genes were registered, including PIK3CA, MAPK, ERBB2, TP53, FANCA, CDKN2A/B, NF1, CTNNB1, etc.
Product Description
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Baryshok Alina S.
Vynnychenko Oleksandr I.
Herman Iryna M.
Denysenko Anastasiia P.
Kozakov Dmytro S.
Livshun Sofiia S.
Moskalenko Roman A.
Moskalenko Yulia V.
Ptaschenchuk Tymofii R.
Smorodska Olha M.
Sulaieva Oksana М.
Chyzhma Ruslana A.
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2024-12-20