Safiye AKTAŞ, Hülya ELLİDOKUZ, İlhan ÖZTOP, İsmail AĞABABAOĞLU, Gökçen ŞİMŞEK ÖMEROĞLU, Duygu DURSUN, Selver ÖZEKİNCİ, Pınar ERÇETİN, Duygu GÜREL, Atila AKKOÇLU

Akciğer adenokarsinomu ve malign plevral mezotelyoma tanısında gen ekspresyon düzeylerinin değerlendirilmesi

Amaç: Bu çalışmada tedavi ve prognozları birbirinden farklı olan akciğer adenokarsinomu ve malign plevral mezotelyomanın ayırıcı tanısında gen ekspresyon düzeylerinin değerlendirilmesi planlandı. Çalışma planı: Ocak 2012 - Ocak 2014 tarihleri arasında akciğer adenokarsinomu ile yeni tanı konan 12 hasta, malign plevral mezotelyomalı 12 hasta ve kontrol grubu olarak sekiz sağlıklı birey çalışmaya alındı. Ribonükleik asit izolasyonu için -80°C’de saklanan taze akciğer adenokarsinom dokuları işlendikten ve malign plevral mezotelyomalı hastaların parafine gömülü dokuları deparafinize edildikten sonra, tamamlayıcı deoksiribonükleik asit sentezi ve deoksiribonükleik asit onarımı ile ilişkili 84 genin ekspresyonu gerçek zamanlı polimeraz zincir reaksiyon testi ile çalışıldı. Her kat değişiminin ekspresyonu tümör hücrelerinin ekspresyonuna göre hesaplandı. Bulgular: BRCA1, BRCA2, CDK7, MLH3, MSH4, NEIL3, SMUG1, UNG, XRCC2 ve XRCC4 genleri, kontrol grubuna kıyasla, akciğer adenokarsinomlu hastalarda beş kattan daha fazla ekspresyon sergiledi. Kontrol grubuna kıyasla, malign plevral mezotelyomalı hastalarda APEX2, BRCA1, BRCA2, CDK7, MLH1, MLH3, MSH3, MSH4, NEIL3, PARP2, PARP3, PMS1, RAD50, RAD51, RAD51B, RAD51D, RAD52, RPA3, SMUG1, UNG, XPA, XRCC2 ve XRCC4 genlerinde beş kat daha fazla ekspresyon izlendi. Malign plevral mezotelyomalı ve akciğer adenokarsinomlu olguların karşılaştırmasında, CDK7, MLH1, TREX1, PRKDC, XPA, PMS1, UNG ve RPA3 genlerinin aşırı eksprese olduğu tespit edildi. Sonuç: Çalışma sonuçlarımız, malign plevral mezotelyoma ve akciğer adenokarsinom hücrelerinde deoksiribonükleik asit onarım genlerinin ekspresyon profilleri arasında farklılıklar olduğunu gösterdi. Çalışma sonuçlarımıza göre, TREX1, PRKDC ve PMS1 genleri bu iki patolojinin ayırıcı tanısında önemli bir rol oynayabilir.

Evaluation of gene expression levels in the diagnosis of lung adenocarcinoma and malignant pleural mesothelioma

Background: This study aims to evaluate gene expression levels in thediagnosis of lung adenocarcinoma and malignant pleural mesothelioma bothwhich have a distinct treatment and prognosis.Methods: Between January 2012 and January 2014, 12 newly diagnosedpatients with a lung adenocarcinoma, 12 patients with malignant pleuralmesothelioma, and eight healthy individuals as the control group wereincluded. After treatment of the fresh samples of lung adenocarcinomastored at -80°C for ribonucleic acid isolation, and paraffin-embedded tissuesof patients with malignant pleural mesothelioma were deparaffinized,complementary deoxyribonucleic acid synthesis and expression of 84 genesassociated with deoxyribonucleic acid repair were analyzed via real-timepolymerase chain reaction assay. According to the expression of tumor cells,expression of each fold change was calculated.Results: The BRCA1, BRCA2, CDK7, MLH3, MSH4, NEIL3, SMUG1,UNG, XRCC2, and XRCC4 genes showed more than five-fold higherexpression in the patients with lung adenocarcinomas, compared to thecontrol group. The patients with malignant pleural mesothelioma showed afive-fold higher expression in the APEX2, BRCA1, BRCA2, CDK7, MLH1,MLH3, MSH3, MSH4, NEIL3, PARP2, PARP3, PMS1, RAD50, RAD51,RAD51B, RAD51D, RAD52, RPA3, SMUG1, UNG, XPA, XRCC2, andXRCC4 genes, compared to the control group. Comparing malignant pleuralmesothelioma with lung adenocarcinoma cases, we found that CDK7, MLH1,TREX1, PRKDC, XPA, PMS1, UNG, and RPA3 genes were overexpressed.Conclusion: Our study results showed differences between expressionprofiles of deoxyribonucleic acid repair genes in lung adenocarcinoma andmalignant pleural mesothelioma cells. Based on our study results, we suggestthat TREX1, PRKDC, and PMS1 genes may play a key role in the differentialdiagnosis of these two entities.

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