Prognostic significance of dysregulation of shelterin complex and its correlation with telomere length and cytogenetics in multiple myeloma.

IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal, genetic engineering & biotechnology Pub Date : 2023-05-03 DOI:10.1186/s43141-023-00504-x
Akanksha A Kalal, Reshma A Shetty, Akshay Bairapura Manjappa, Nagaraj V Kulkarni, Prashanth Shetty
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Abstract

Background: MM (multiple myeloma) is a bone marrow disease with the accumulation of malignant plasma cells characterized by the neoplastic transformation of differentiated B cells. The onset and progression of cancer are greatly influenced by telomere dysfunction. We aimed to study the biomarker potential and prognostic significance of shelterin complex and hTERT. Telomere length and gene expression were measured using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and these results were further correlated with clinical parameters.

Results: Our study showed increased expression of all genes in complex, hTERT, and TL in MM (n = 72) in comparison with controls (n = 31). TRF2 (P = 0.025) and hTERT (P = 0.0002) displayed significant association among cytogenetic analysis. The receiver operative curve showed POT1 and RAP1 with a greater area under the curve (AUC). RAP1 (P = 0.020) and hTERT (P = 0.037) displayed to be independent prognostic markers for overall survival. Clinical parameters and genes were observed to be significantly correlated.

Conclusion: Our study findings showed variation in telomere-associated genes and suggest the participation of these genes as prognostic markers in MM. These results all together highlight the evaluation and role of genes involved in telomeric alteration and TL, providing the opportunity to study new therapeutic approaches in patients with MM.

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多发性骨髓瘤中庇护蛋白复合物失调的预后意义及其与端粒长度和细胞遗传学的相关性。
背景:多发性骨髓瘤是一种以恶性浆细胞积聚为特征的骨髓疾病,其特征为分化的B细胞的肿瘤转化。端粒功能障碍对癌症的发生和发展有很大的影响。我们的目的是研究庇护蛋白复合物和hTERT的生物标志物潜力和预后意义。采用实时定量逆转录聚合酶链反应(RT-qPCR)检测端粒长度和基因表达,并进一步与临床参数进行相关性分析。结果:我们的研究显示,与对照组(n = 31)相比,MM (n = 72)中complex、hTERT和TL中所有基因的表达均有所增加。TRF2 (P = 0.025)和hTERT (P = 0.0002)在细胞遗传学分析中有显著相关性。受者工作曲线显示POT1和RAP1,曲线下面积(AUC)较大。RAP1 (P = 0.020)和hTERT (P = 0.037)是总生存期的独立预后指标。临床参数与基因有显著相关性。结论:我们的研究结果显示端粒相关基因的变异,并提示这些基因参与了MM的预后标记。这些结果共同强调了端粒改变和TL相关基因的评估和作用,为MM患者研究新的治疗方法提供了机会。
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