Abnormal mRNA Expression Levels of Telomere-Binding Proteins Represent Biomarkers in Myelodysplastic Syndromes: A Case-Control StudyBaoshan Liu1, Rongdi Yan2, Jie Zhang3, Bin Wang4, Hu Sun5, Xing Cui31Tianjin Medical University General Hospital, Clinic of Traditional Chinese Medicine, Tianjin, China
2The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Respiratory Disease, Jinan, China
3Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Hematology, Jinan, China
4Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Peripheral Vascular Disease, Jinan, China
5Shandong Institute of Traditional Chinese Medicine, Department of Pharmacology, Jinan, China
Objective: As evidence was shown that abnormal shortening of telomeres begins to accumulate in myelodysplastic syndrome (MDS) patients, this study was conducted to determine the relationship between the mRNA expression levels of telomere-binding proteins (TRF1/TRF2/TIN2/TPP1/POT1/RAP1) and the risk level in MDS.
Materials and Methods: There were 40 patients with MDS and 40 normal controls in this study. Methods including telomere content assays and quantitative reverse transcription-polymerase chain reaction were used to examine the mRNA levels of TRF1/TRF2/TIN2/ TPP1/POT1/RAP1 in patients with MDS.
Results: Compared to the normal group used as a control, the mRNA expression levels of RAP1/POT1/TPP1 of the patients with MDS were decreased, whereas their levels of TRF1/TRF2 and TIN2 were increased. A positive correlation was found between the TRF1, TRF2, and TIN2 mRNA expression levels and the risk level of the International Prognostic Scoring System (IPSS) and the World Health Organization Prognostic Scoring System (WPSS) criteria; however, a negative correlation was found between RAP1/POT1/TPP1 mRNA expression levels and the risk levels of IPSS and WPSS criteria.
Conclusion: Because the reduction of TRF1/TRF2/TIN2 mRNA expression and the increase of RAP1/POT1/TPP1 mRNA expression are closely related to the risk levels of the IPSS and WPSS criteria in MDS, it is thought that these telomere-binding proteins could lead to abnormal telomere length and function, which cause chromosomal abnormalities in MDS. With this evidence, we suggest that those proteins’ mRNA expressions could be used as biomarkers for the assessment of the risk degree of MDS patients.
Keywords: Myelodysplastic syndromes, Telomere-binding proteins, Reverse transcription-polymerase chain reaction, International Prognostic Scoring System, World Health Organization Prognostic Scoring System
Miyelodisplastik Sendromda Biyobelirteç Olarak Telomer-Bağlayıcı Proteinlerine Ait Anormal mRNA Ekspresyon Düzeyleri: Olgu-Kontrol ÇalışmasıBaoshan Liu1, Rongdi Yan2, Jie Zhang3, Bin Wang4, Hu Sun5, Xing Cui31Tianjin Medical University General Hospital, Clinic of Traditional Chinese Medicine, Tianjin, China
2The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Respiratory Disease, Jinan, China
3Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Hematology, Jinan, China
4Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Peripheral Vascular Disease, Jinan, China
5Shandong Institute of Traditional Chinese Medicine, Department of Pharmacology, Jinan, China
Amaç: Miyelodisplastik sendrom (MDS) hastalarında Telomerlerin anormal olarak kısalması ile ilgili kanıtlar giderek artmaktadır. Bu çalışma telomer bağlayıcı proteinlerin (TRF1/TRF2/TIN2/TPP1/POT1/ RAP1) mRNA ekspresyon düzeyleri ile MDS risk skorları arasındaki ilişkinin tespit edilmesi amacıyla yapıldı.
Gereç ve Yöntem: Bu çalışmaya 40 MDS hastası ve 40 normal kontrol dahil edildi. MDS hastalarında telomer içerik tahlilleri ve kantitatif ters transkripsiyon-polimeraz zincir reaksiyonu TRF1/TRF2/ TIN2/TPP1/POT1/RAP1 mRNA düzeylerini incelemek için kullanıldı.
Bulgular: Normal grup kontrol olarak kullanıldı, MDS hastalarında RAP1/POT1/TPP1 mRNA ekspresyon düzeyleri azalmış, ancak sırasıyla TRF1/TRF2 ve TIN2 düzeyleri artmıştı. TRF1, TRF2 ve TIN2 mRNA ekspresyon düzeyleri ile Uluslararası Prognoz Skorlama Sistemi (UPSS) ve Dünya Sağlık Örgütü Prognoz Skorlama Sistemi (DPSS) arasında pozitif korelasyon tespit edildi, RAP1/POT1/TPP1 mRNA ekspresyon düzeyleri ile UPSS ve DPSS kriterleri arasında negatif bir korelasyon bulundu.
Sonuç: MDS’de TRF1/TRF2/TIN2 mRNA ekspresyonunun azalması ve RAP1/POT1/TPP1 mRNA ekspresyonunun artışı ile UPSS ve DPSS kriterleri arasında yakın bir ilişki bulunması, bu telomerbağlayıcı proteinlerin MDS’de kromozomal anormalliklere sebep olabilecek anormal telomer boy ve fonksiyonları oluşmasına yol açabileceğini düşündürmektedir. Bu nedenle biz bu proteinlerin mRNA ekspresyonlarının MDS hastalarının risk değerlendirmesinde biyobelirteç olarak kullanılabileceğini düşünmekteyiz.
Anahtar Kelimeler: Miyelodisplastik sendromlar, Telomer-bağlayıcı proteinler, Ters transkripsiyon-polimeraz zincir reaksiyonu, Uluslararası Prognoz Skorlama Sistemi, Dünya Sağlık Örgütü Prognoz Skorlama Sistemi
Baoshan Liu, Rongdi Yan, Jie Zhang, Bin Wang, Hu Sun, Xing Cui. Abnormal mRNA Expression Levels of Telomere-Binding Proteins Represent Biomarkers in Myelodysplastic Syndromes: A Case-Control Study. Turk J Hematol. 2017; 34(3): 200-206
Corresponding Author: Xing Cui, China |
|