Beyin tümöründe gst-t1, gst-m1 ve p53 proteinlerinin rolü
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Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Kırıkkale Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Oldukça riskli ve önemli kanser türlerinden biri olan beyin kanserinde tümör baskılayıcı p53 ile detoksifikasyon mekanizmasında görev alan Glutatyon S-Transferaz (GST) enzim ailesinin üyelerinin rollerinin araştırılması amaçlanmıştır. Beyin tümörlü hasta dokularında mitakondriyal GST izozimlerinden GST Mü-1 (GSTM1), GST Teta-1 (GSTT1) ve p53'ün protein ekspresyonları ile yine bu izozimlerin moleküler düzeyde delesyon ve nokta mutasyon (SNP) analizleri yapılarak enzim düzeyindeki ekspresyon durumları karşılaştırmalı olarak değerlendirilmiştir. Bu veriler hastaların bazı demografik ve klinik verileri ile de istatistiksel olarak değerlendirilmiştir. Çalışmamızda 142 beyin tümörlü hastanın 83 (%58,45)'i erkek, 59 (41,55)'u kadın hastalardan oluşmakta olup, hastaların yaş ortalamaları 49,44±8,09 dur. İmmunohistokimyasal analizler sonucu, GST-T ekspresyonu tümörlü dokularda normal dokulara göre 9,46 kat artışa neden olurken, bu artışın tümörlü dokulara sahip hastalarda hayatta kalım oranının ise anlamlı derecede azaldığı gözlemlenmiştir. GST-T protein ekspresyonunda, 60 yaş üzeri hastalarda anlamlı derecede ekspresyon artışı gözlemlenirken, kemoterapi tedavisi bu enzim ekspresyonunun artışına neden olduğu da belirlenmiştir. Normal dokularda tümörlü dokulara oranla diğer parametrelerden bağımsız olarak daha fazla p53 protein ekspresyonuna rastlandı. Özellikle hastaların GST-M delesyon durumları anlamlı şekilde gen kaybına uğrayarak, önemli ölçüde "null" allen frekansı gözlemlenmiştir (p<0,005). GST-M gen bölgesinde beyin tümörlü hastalarda 66(%44,3) "null" allele rastlanırken, GST-T gen bölgesinde bu sayı 7 (%4,9) şeklinde gözlemlenmiştir. GSTM1 null allel frekansı kadınlarda erkeklere göre daha sık olduğu gözlemlenmiştir [OR: 1.640 (0.837-3.215)]. GSTM1 "null" allel frekansına radyoterapi alan hastalarda almayanlara göre daha sık olduğu belirlenmiştir [OR=1.076 (0.548-2.114)]. GSTT1 "null" allel sıklığı kadınlarda daha yüksek olduğu belirlenmiştir [OR=1.105 (0.238-5.130)]. GSTT1 "null" allel frekansına 60 yaşın altındaki hastalarda daha yüksek olarak gözlemlenmiştir [OR=1.364 (0.255-7.296)]. GSTT1 "null" allel frekansına ise alkol tüketicilerinde daha sık olarak rastlanmıştır [OR=1.564 (0.175-14.016)]. GSTT1 "null" alleli, radyoterapi alan hastalarda daha sık şekilde gözlemlenmiştir [OR=1.212 (0.261-5.631)]. GSTT1 "null" allel frekansı kemoterapi alan hastalarda daha sık gözlemlenmiştir [OR=1.413 (0.261-7.653)]. GSTT1 "null" genotipi yaşayan hastalarda daha az sıklıkta bulunmuştur [OR=0.704 (0.151-3.278]. Tümör supresor p53 geninin genotip dağılımı şu şekilde belirlenmiştir: Arg/Pro (Heterozigot) %58.3. Arg /Arg (Vahşi Tip) %25.8 ve Pro/Pro (Mutant Tip) %15,8 şeklinde bulunmuştur. Pro kodlayan allel sıklığı ise hasta grubunda 0.45, kontrol grubunda 0.37 olarak bulunmuştur. Hasta grubunda kontrol grubuna göre Arg/Pro, Arg/Arg'dan 1.767 kat daha yüksektir. Pro/Pro, kontrol grubuna göre, hasta grubunda Arg/Arg'dan 1.839 kat daha yüksekti. Hastaların kontrol grubuna göre p53 ekzon4 kodon72 (SNP) gen bölgesinde guanin/sitozin dönüşümünden kaynaklı, mutasyon bir miktar yüksek olmasına rağmen anlamlı bir fark bulunamamıştır. Önemli rollerine rağmen, henüz bu enzimlerin ve gen bölgelerinin, beyin tümörü arasındaki ilişki üzerine yapılmış özellikle Türkiye'de geniş kapsamlı çalışma yoktur. Çalışmanın bölgesel anlamda yapılan çalışmalar kapsamında önemli bir yere sahip olduğu göz önüne alındığında, orijinalite açısından özgün değerinin yüksek olduğu düşünülmektedir.
It is aimed to investigate the roles of the members of the Glutathione S-Transferase (GST) enzyme family, which is involved in the detoxification mechanism with the tumor suppressor p53 in brain cancer, which is one of the most risky and important cancer types. Protein expressions of mitochondrial GST isozymes GST Mü-1 (GSTM1), GST Theta-1 (GSTT1) and p53 in patients with brain tumor and deletion and point mutation (SNP) analyzes of these isozymes at the molecular level were evaluated comparatively. These data were statistically evaluated with some demographic and clinical data of the patients. In our study, 83 (58.45%) of 142 brain tumor patients were male and 59 (41.55) were female, and the mean age of the patients was 49.44±8.09. As a result of immunohistochemical analyzes, GST-T expression caused an increase of 9.46 times in tumor tissues compared to normal tissues, while it was observed that this increase significantly decreased the survival rate in patients with tumor tissues. While a significant increase in GST-T protein expression was observed in patients over 60 years of age, it was also determined that chemotherapy treatment caused an increase in this enzyme expression. More p53 protein expression was found in normal tissues compared to tumor tissues, independent of other parameters. In particular, the GST-M deletion status of the patients suffered significant gene loss, and a significant "null" allen frequency was observed (p<0.005). While 66 (44.3%) "null" alleles were found in the GST-M gene region in patients with brain tumors, this number was observed as 7 (4.9%) in the GST-T gene region. The GSTM1 null allele frequency was observed to be more frequent in females than males [OR: 1,640 (0.837-3.215)]. It was determined that it was more common in patients who received radiotherapy to the GSTM1 "null" allele frequency [OR=1.076 (0.548-2.114)]. The frequency of the GSTT1 "null" allele was found to be higher in females [OR=1.105 (0.238-5.130)]. The GSTT1 "null" allele frequency was observed to be higher in patients younger than 60 years [OR=1.364 (0.255-7.296)]. GSTT1 "null" allele frequency was found more frequently in alcohol consumers [OR=1.564 (0.175-14.016)]. The GSTT1 "null" allele was observed more frequently in patients receiving radiotherapy [OR=1.212 (0.261-5.631)]. The GSTT1 "null" allele frequency was observed more frequently in patients receiving chemotherapy [OR=1.413 (0.261-7.653)]. GSTT1 was found to be less common in patients with the "null" genotype [OR=0.704 (0.151-3.278]. The genotype distribution of the tumor suppressor p53 gene was determined as follows: Arg/Pro (Heterozygous) 58.3%, Arg/Arg (Wild Type) 25.8% and Pro/Pro (Mutant Type) was found to be 15.8%.The frequency of Pro-coding allele was 0.45 in the patient group and 0.37 in the control group. Arg/Pro was 1.767 times higher than Arg/Arg in the patient group compared to the control group. Pro was 1.839 times higher than Arg/Arg in the patient group compared to the control group, although the mutation due to guanine/cytosine conversion in the p53 exon4 codon72 (SNP) gene region of the patients was slightly higher, but no significant difference was found. Despite their important roles, there is not yet a comprehensive study on the relationship between these enzymes and gene regions and brain tumor, especially in Turkey. Considering its originality, it is thought to have a high original value in terms of originality.
It is aimed to investigate the roles of the members of the Glutathione S-Transferase (GST) enzyme family, which is involved in the detoxification mechanism with the tumor suppressor p53 in brain cancer, which is one of the most risky and important cancer types. Protein expressions of mitochondrial GST isozymes GST Mü-1 (GSTM1), GST Theta-1 (GSTT1) and p53 in patients with brain tumor and deletion and point mutation (SNP) analyzes of these isozymes at the molecular level were evaluated comparatively. These data were statistically evaluated with some demographic and clinical data of the patients. In our study, 83 (58.45%) of 142 brain tumor patients were male and 59 (41.55) were female, and the mean age of the patients was 49.44±8.09. As a result of immunohistochemical analyzes, GST-T expression caused an increase of 9.46 times in tumor tissues compared to normal tissues, while it was observed that this increase significantly decreased the survival rate in patients with tumor tissues. While a significant increase in GST-T protein expression was observed in patients over 60 years of age, it was also determined that chemotherapy treatment caused an increase in this enzyme expression. More p53 protein expression was found in normal tissues compared to tumor tissues, independent of other parameters. In particular, the GST-M deletion status of the patients suffered significant gene loss, and a significant "null" allen frequency was observed (p<0.005). While 66 (44.3%) "null" alleles were found in the GST-M gene region in patients with brain tumors, this number was observed as 7 (4.9%) in the GST-T gene region. The GSTM1 null allele frequency was observed to be more frequent in females than males [OR: 1,640 (0.837-3.215)]. It was determined that it was more common in patients who received radiotherapy to the GSTM1 "null" allele frequency [OR=1.076 (0.548-2.114)]. The frequency of the GSTT1 "null" allele was found to be higher in females [OR=1.105 (0.238-5.130)]. The GSTT1 "null" allele frequency was observed to be higher in patients younger than 60 years [OR=1.364 (0.255-7.296)]. GSTT1 "null" allele frequency was found more frequently in alcohol consumers [OR=1.564 (0.175-14.016)]. The GSTT1 "null" allele was observed more frequently in patients receiving radiotherapy [OR=1.212 (0.261-5.631)]. The GSTT1 "null" allele frequency was observed more frequently in patients receiving chemotherapy [OR=1.413 (0.261-7.653)]. GSTT1 was found to be less common in patients with the "null" genotype [OR=0.704 (0.151-3.278]. The genotype distribution of the tumor suppressor p53 gene was determined as follows: Arg/Pro (Heterozygous) 58.3%, Arg/Arg (Wild Type) 25.8% and Pro/Pro (Mutant Type) was found to be 15.8%.The frequency of Pro-coding allele was 0.45 in the patient group and 0.37 in the control group. Arg/Pro was 1.767 times higher than Arg/Arg in the patient group compared to the control group. Pro was 1.839 times higher than Arg/Arg in the patient group compared to the control group, although the mutation due to guanine/cytosine conversion in the p53 exon4 codon72 (SNP) gene region of the patients was slightly higher, but no significant difference was found. Despite their important roles, there is not yet a comprehensive study on the relationship between these enzymes and gene regions and brain tumor, especially in Turkey. Considering its originality, it is thought to have a high original value in terms of originality.
Açıklama
Fen Bilimleri Enstitüsü, Biyoloji Ana Bilim Dalı
Anahtar Kelimeler
Moleküler Tıp, Molecular Medicine
