乳腺癌干细胞及部分相关分子生物标志物在转移性和非转移性乳腺癌中的作用。

The Role of Breast Cancer Stem Cells and Some Related Molecular Biomarkers in Metastatic and Nonmetastatic Breast Cancer.

机构信息

Cell Biology and Histology, Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt.

Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

Clin Breast Cancer. 2020 Aug;20(4):e373-e384. doi: 10.1016/j.clbc.2019.11.008. Epub 2020 Mar 12.

DOI:10.1016/j.clbc.2019.11.008

PMID:32299754

Abstract

BACKGROUND

Breast cancer stem cells (BCSCs) play important role(s) in the development and progression of invasive duct carcinoma (IDC). We assessed the role of BCSC marker expression and the number of mammospheres in cultures of breast cancer (BC) tissues and correlated these data to relevant clinicopathologic features of the patients and overall survival (OS).

METHODS

Fresh tumor tissue samples were collected from 44 Egyptian female patients with IDC of the breast and 25 healthy women undergoing reduction mammoplasty as a control. The mammosphere number and the RNA expression levels of some cancer stem cell-related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) were assessed by reverse-transcriptase polymerase chain reaction at different stages of BCSC differentiation compared with control samples.

RESULTS

The number of CD44CD24 cells associated significantly at the end of culture with the expression level of Wnt, β-catenin, and distant metastasis (P < .001, P = .015 and P = .003, respectively). There was significant association between the mammosphere number and CD44CD24 cells as well as AKT expression (P = .040 and .021, respectively). PTEN messenger RNA expressed significantly in BC (P < .05). Wnt-RNA expression associated significantly with high tumor stage, positive lymph node status, Her2-neu overexpression, and metastasis (P = .009, .012, .026, and .001, respectively), whereas OS associated significantly with distant metastasis, Wnt, and PTEN expressions (P < .001, P = .001, P = .014, respectively).

CONCLUSION

BCSCs and their related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) play important roles in the development and progression of BC and they can be used as potential prognostic and predictive biomarkers for patients with BC or as target therapy.

摘要

背景

乳腺癌干细胞（BCSCs）在浸润性导管癌（IDC）的发展和进展中发挥重要作用。我们评估了 BCSC 标志物表达和乳腺癌（BC）组织培养中类乳腺球体的数量，并将这些数据与患者的相关临床病理特征和总生存（OS）相关联。

方法

从 44 名埃及女性 IDC 乳腺癌患者和 25 名接受乳房缩小成形术的健康女性的新鲜肿瘤组织样本中收集组织样本。通过逆转录聚合酶链反应（RT-PCR）在不同的 BCSC 分化阶段评估一些癌症干细胞相关基因（PTEN、PI3K、AKT、Wnt 和 β-catenin）的 RNA 表达水平，并与对照样本进行比较。

结果

在培养结束时，CD44CD24 细胞的数量与 Wnt、β-catenin 和远处转移的表达水平显著相关（P<0.001、P=0.015 和 P=0.003）。类乳腺球体的数量与 CD44CD24 细胞和 AKT 表达之间存在显著相关性（P=0.040 和 P=0.021）。BC 中 PTEN 信使 RNA 表达显著（P<0.05）。Wnt-RNA 表达与高肿瘤分期、阳性淋巴结状态、Her2-neu 过表达和转移显著相关（P=0.009、P=0.012、P=0.026 和 P=0.001），而 OS 与远处转移、Wnt 和 PTEN 表达显著相关（P<0.001、P=0.001、P=0.014）。