循环 miR-106a 和 Raf-1 作为乳腺癌诊断和预后标志物的临床评估。
A Clinical Evaluation of Circulating MiR-106a and Raf-1 as Breast Cancer Diagnostic and Prognostic Markers.
机构信息
Department of Central Labs, National Nutrition Institute, Cairo, Egypt.
Department of Biochemistry, Faculty of Science, Helwan University, Cairo, Egypt.
出版信息
Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3513-3520. doi: 10.31557/APJCP.2021.22.11.3513.
OBJECTIVE
MicroRNAs (MiRNAs) regulate mammalian cell growth, differentiation, and apoptosis by altering the expression of other genes and serve multiple roles in tumorigenesis and progression. Proto-oncogene serine/threonine-protein kinase (RAF-1) functions as a part of the MAPK/ERK signal transduction pathway. The present study aim was to prospectively evaluate MicroRNA 106a (MiR-106a) and RAF-1 as a diagnostic and prognostic factor in early prediction of breast cancer (BC), recurrence and early detection of distant metastasis as well as to analyses the statistical correlation between MiR-106a and RAF-1 levels and clinical-pathological parameters including tumor size, lymph node, histological type and grading.
METHODS
Sera and plasma of 30 normal women and 50 women with breast carcinoma were assayed for MiR-106a by RT-qPCR as well as levels of Hb, WBCs and platelets count and RAF-1 by solid phase enzyme-linked immunosorbent assay (ELISA).
RESULTS
The patients' characteristics, they were classified according to grade into 8% grade I, 66% grade II, 22% grade III and 4% grade IV. The stages were classified according to the TNM system as stage II was the highest percentage 66%, while the lowest percentage was 10% for stage I and 24% for stage III. Also, Hb% and RAF-1 levels were significantly decreased in breast cancer patients as compared with healthy control. On the other hand, MiRNA-106a gene expression was non-significantly increased in positive lymph node metastasis patients (FC=3.66) when compared to patients with negative lymph node metastasis (FC=3.51). In addition, MiR-106a was significantly up-regulated in breast cancer patients with a fold of change 3.63 when compared to control samples.
CONCLUSION
Expression of MiR-106a gene can be used as a diagnostic and prognostic noninvasive biomarker which can stimulates breast cancer cell invasion and proliferation through downregulation of Raf-1 levels.
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目的
MicroRNAs（miRNAs）通过改变其他基因的表达来调节哺乳动物细胞的生长、分化和凋亡，在肿瘤发生和进展中发挥多种作用。原癌基因丝氨酸/苏氨酸蛋白激酶（RAF-1）作为 MAPK/ERK 信号转导途径的一部分发挥作用。本研究旨在前瞻性评估 microRNA-106a（miR-106a）和 RAF-1 作为乳腺癌（BC）早期预测的诊断和预后因素，以及复发和远处转移的早期检测，并分析 miR-106a 和 RAF-1 水平与临床病理参数之间的统计学相关性，包括肿瘤大小、淋巴结、组织学类型和分级。
方法
通过 RT-qPCR 检测 30 例正常女性和 50 例乳腺癌患者血清和血浆中的 miR-106a 水平，以及固相酶联免疫吸附试验（ELISA）检测 RAF-1 水平。
结果
患者特征，根据分级分为 8%的 I 级、66%的 II 级、22%的 III 级和 4%的 IV 级。根据 TNM 系统分期，II 期为最高比例 66%，而 I 期和 III 期的最低比例分别为 10%和 24%。此外，与健康对照组相比，乳腺癌患者的 Hb%和 RAF-1 水平显著降低。另一方面，与无淋巴结转移的患者相比，有淋巴结转移的阳性患者的 miRNA-106a 基因表达水平升高（FC=3.66）。此外，与对照样本相比，乳腺癌患者的 miR-106a 表达水平显著上调，倍数变化为 3.63。
结论
miR-106a 基因的表达可以作为一种诊断和预后的非侵入性生物标志物，通过下调 Raf-1 水平，刺激乳腺癌细胞的侵袭和增殖。
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