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端粒保护蛋白复合体失调在多发性骨髓瘤中的预后意义及其与端粒长度和细胞遗传学的相关性

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

作者信息

Kalal Akanksha A, Shetty Reshma A, Manjappa Akshay Bairapura, Kulkarni Nagaraj V, Shetty Prashanth

机构信息

KSHEMA Center for Genetic Services, KS Hegde Medical Academy, NITTE (Deemed to Be University), Mangaluru, Karnataka, India.

Department of Anatomy, KS Hegde Medical Academy, NITTE (Deemed to Be University), Mangaluru, Karnataka, India.

出版信息

J Genet Eng Biotechnol. 2023 May 3;21(1):50. doi: 10.1186/s43141-023-00504-x.

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.

摘要

背景

多发性骨髓瘤(MM)是一种骨髓疾病,其特征是恶性浆细胞积累,由分化的B细胞发生肿瘤转化引起。癌症的发生和进展受端粒功能障碍的极大影响。我们旨在研究端粒保护蛋白复合体和人端粒酶逆转录酶(hTERT)作为生物标志物的潜力及其预后意义。使用实时定量逆转录聚合酶链反应(RT-qPCR)测量端粒长度和基因表达,并将这些结果与临床参数进一步关联。

结果

我们的研究表明,与对照组(n = 31)相比,MM组(n = 72)中端粒保护蛋白复合体、hTERT和端粒长度(TL)的所有基因表达均增加。在细胞遗传学分析中,端粒重复结合因子2(TRF2,P = 0.025)和hTERT(P = 0.0002)显示出显著相关性。受试者工作曲线显示,端粒保护蛋白1(POT1)和端粒相关蛋白1(RAP1)的曲线下面积(AUC)更大。RAP1(P = 0.020)和hTERT(P = 0.037)被证明是总生存期的独立预后标志物。临床参数与基因之间存在显著相关性。

结论

我们的研究结果显示端粒相关基因存在差异,并表明这些基因作为MM预后标志物的参与情况。这些结果共同突出了参与端粒改变和端粒长度的基因的评估及其作用,为研究MM患者的新治疗方法提供了机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb02/10154441/dd3db83ed92d/43141_2023_504_Fig1_HTML.jpg

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