Publication: Meme kanserinde ıgfbp7 metilasyonu ve telomer uzunluğu ile ilişkisi
Abstract
Meme Kanserinde IGFBP7 Metilasyonu ve Telomer Uzunluğu İle İlişkisi 1.Amaç: IGFBP7 ekspresyonu ve telomer ÖZET uzunluğu (TL) varyasyonu meme kanserinde yaygın görülen moleküler değişimlerdir. Bu çalışmanın amacı IGFBP7 geni metilasyon durumu, telomer uzunluğu ve klinik özellikler arasındaki olası ilişkiyi araştırmaktır. Gereç ve Yöntem: Dokuların tümör ve komşu sağlıklı örnekleri, metilasyon spesifik PZR ile IGFBP7 metilasyonu için (n=61), Western blotlama ile IGFBP7 ekspresyon durumu için (n=28) ve kantitatif PZR ile TL durumu için (n=100) analiz edilmiştir. Bulgular: IGFBP7 metilasyonu tümör dokularının %90’nında gözlenirken, komşu sağlıklı dokularda %59 olarak bulunmuştur (p=0,0002). IGFBP7 promotorunun hastaların %62,3’ünde hem kanserli dokuda hem de komşu sağlıklı dokuda metilasyon durumu aynı, %37,7’sinde (n=23/ 61) ise sadece tümörde metile bulunmuştur. Bununla birlikte tümör doku ve komşu sağlıklı doku arasındaki metilasyon farklılığının hem gen ekspresyonu hem de klinikopatolojik parametreler ile önemli bir ilişkisi bulunamamıştır. Telomer sağlıklı dokular ve kanserli dokular arasında karşılaştırıldığında, kanserli dokularda önemli oranda daha kısa olduğu belirlenmiştir (p=0,0002). Komşu sağlıklı dokulara göre tümörde TL, tümör çapıyla ters orantılı ve ileri evredeki meme kanserinde anlamlı derecede daha kısa olduğu görülmüştür. Bununla birlikte TL tümör çapı küçük (p>0,05), ilk evredeki ve IDC’lı meme kanserinde daha uzun saptanmıştır (p<0,05). Sonuç: Sonuç olarak, IGFBP7 promotor metilasyonu ve daha kısa telomerler meme kanseri gelişmesinde bir biyobelirteç olabilir. Komşu sağlıklı örneklerine göre tümörde daha uzun telomerler ve IGFBP7 metilasyonu invaziv duktal meme kanseri gelişmesinde önemli bir rol oynayabilir. Bu ilişkinin aydınlatılabilmesi için daha fazla sayıda vaka içeren çalışmalara ihtiyaç vardır. Meme kanseri, IGFBP7, metilasyon, telomer, telomer uzunluğu. 1.
IGFBP7 Methylation in Breast Cancer and Its Association with Telomere Length. Aim: Variation of IGFBP7 expression and telomere length (TL) are common molecular alterations in breast cancer. The aim of this study was to investigate a potential association between promoter methylation status of IGFBP7 gene, telomere length and clinical parameters. Methods: Tumor and adjacent-healthy samples of tissues were evaluated for IGFBP7 methylation status (n=61) by the methylation-specific PCR, for IGFBP7 expression status (n=28) by Western blotting, and for telomere length (n=100) status by quantitative PCR. Results: IGFBP7 methylation was observed in 90% of tumor tissues and 59% of adjacent healthy tissues (p=0.0002). IGFBP7 promoter methylation was identical for both tumor and healthy tissues in 62.3% of patients, whereas in the other patients (37.7%, n=23/ 61) was methylated in only tumor tissues. However IGFBP7 methylation difference between tumor and adjacent healthy tissues was not associated both the gene expression and clinicopathologic parameters. Telomeres were shorter in tumor tissues compared to adjacent healthy tissues (calibrator: median healthy tissues ΔCt, p=0.0002). TL in tumor compared with adjacent tissues was shorter in BC with major tumor size and advanced stage (p<0.05). However, TL was longer in breast cancer with small tumor size (p>0.05), first stage and IDC (p<0.05). Conclusion: These results suggest that IGFBP7 promoter methylation and shorter TL may be predictive biomarker for the development of breast cancer. Alteration of TL in tumor compared with adjacent tissues and IGFBP7 methylation may play an important role in the pathogenesis of invasive ductal breast cancer. Studies concerning larger numbers of cases are necessary to clarify this association. Key words: Breast cancer, IGFBP7, methylation, telomere, telomere length.
IGFBP7 Methylation in Breast Cancer and Its Association with Telomere Length. Aim: Variation of IGFBP7 expression and telomere length (TL) are common molecular alterations in breast cancer. The aim of this study was to investigate a potential association between promoter methylation status of IGFBP7 gene, telomere length and clinical parameters. Methods: Tumor and adjacent-healthy samples of tissues were evaluated for IGFBP7 methylation status (n=61) by the methylation-specific PCR, for IGFBP7 expression status (n=28) by Western blotting, and for telomere length (n=100) status by quantitative PCR. Results: IGFBP7 methylation was observed in 90% of tumor tissues and 59% of adjacent healthy tissues (p=0.0002). IGFBP7 promoter methylation was identical for both tumor and healthy tissues in 62.3% of patients, whereas in the other patients (37.7%, n=23/ 61) was methylated in only tumor tissues. However IGFBP7 methylation difference between tumor and adjacent healthy tissues was not associated both the gene expression and clinicopathologic parameters. Telomeres were shorter in tumor tissues compared to adjacent healthy tissues (calibrator: median healthy tissues ΔCt, p=0.0002). TL in tumor compared with adjacent tissues was shorter in BC with major tumor size and advanced stage (p<0.05). However, TL was longer in breast cancer with small tumor size (p>0.05), first stage and IDC (p<0.05). Conclusion: These results suggest that IGFBP7 promoter methylation and shorter TL may be predictive biomarker for the development of breast cancer. Alteration of TL in tumor compared with adjacent tissues and IGFBP7 methylation may play an important role in the pathogenesis of invasive ductal breast cancer. Studies concerning larger numbers of cases are necessary to clarify this association. Key words: Breast cancer, IGFBP7, methylation, telomere, telomere length.