KLF11 is an independent negative prognostic factor for breast cancer from a cohort study and induces proliferation and inhibits apoptosis in vitro,Breast Cancer

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KLF11 is an independent negative prognostic factor for breast cancer from a cohort study and induces proliferation and inhibits apoptosis in vitro
Breast Cancer ( IF 4.0 ) Pub Date : 2023-05-18 , DOI: 10.1007/s12282-023-01470-5
Lili Lin ₁ , Kristina Pfender ₁ , Nina Ditsch ₂ , Christina Kuhn ₂ , Martina Rahmeh ₁ , Lin Peng ₁ , Elisa Schmoeckel ₃ , Doris Mayr ₃ , Fabian Trillsch ₁ , Sven Mahner ₁ , Mirjana Kessler ₁ , Udo Jeschke _{1,

2} , Anna Hester ₁

Affiliation

Background

The therapy concepts that target several members of krüppel like factor (KLF) family have been achieved in breast cancer (BC). However, the role of KLF11 in BC remains unclear. This study explored the prognostic significance of KLF11 in BC patients and investigated its functional roles in this malignancy.

Methods

Immunohistochemistry (IHC) staining of KLF11 in 298 patients’ samples was performed to determine the prognostic role of the KLF11. Then the protein level was correlated to clinicopathological characteristics and survival outcomes. Afterward, the function of KLF11 was explored in vitro with siRNA-mediated loss-of-function of cell viability, proliferation, and apoptosis.

Results

From the cohort study, we found that the expression of KLF11 was positively associated with highly proliferative BC of BC. Furthermore, prognostic analysis demonstrated that KLF11 was an independent negative factor for disease-free survival (DFS) and distant-metastasis-free survival (DMFS) of BC. The KLF11-related prognostic model for DFS and DMFS showed high accuracy in predicting the 3-,5- and 10 -year survival probability of BC patients. Additionally, the knockdown of KLF11 inhibited cell viability and proliferation, as well as induced cell apoptosis in MCF7 and MDA-MB-231 cells, while only inhibited cell viability and induced cell apoptosis in SK-BR-3 cells.

Conclusions

Our study indicated that targeting KLF11 is an interesting therapeutic concept and further research could lead to a new therapeutic improvement in BC, especially in highly aggressive molecular subtypes.

中文翻译：

一项队列研究表明，KLF11 是乳腺癌的独立负面预后因素，在体外诱导增殖并抑制细胞凋亡

背景

针对 krüppel 样因子 (KLF) 家族的几个成员的治疗概念已在乳腺癌 (BC) 中实现。然而，KLF11 在 BC 中的作用仍不清楚。本研究探讨了 KLF11 在 BC 患者中的预后意义，并调查了其在这种恶性肿瘤中的功能作用。

方法

对 298 名患者样本中的 KLF11 进行免疫组织化学 (IHC) 染色，以确定 KLF11 的预后作用。然后蛋白质水平与临床病理特征和生存结果相关。随后，通过 siRNA 介导的细胞活力、增殖和凋亡功能丧失，在体外探索了 KLF11 的功能。

结果

从队列研究中我们发现KLF11的表达与BC的高度增殖呈正相关。此外，预后分析表明KLF11是BC无病生存（DFS）和无远处转移生存（DMFS）的独立负面因素。KLF11 相关的 DFS 和 DMFS 预后模型在预测 BC 患者的 3 年、5 年和 10 年生存概率方面显示出较高的准确性。此外，在MCF7和MDA-MB-231细胞中，KLF11的敲低抑制细胞活力和增殖，并诱导细胞凋亡，而在SK-BR-3细胞中仅抑制细胞活力并诱导细胞凋亡。