敲低激酶家族 15 抑制体外癌细胞增殖及其在三阴性乳腺癌中的临床相关性。

Knockdown of Kinase Family 15 Inhibits Cancer Cell Proliferation In vitro and its Clinical Relevance in Triple-Negative Breast Cancer.

机构信息

Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Shanghai, China.

出版信息

Curr Mol Med. 2019;19(2):147-155. doi: 10.2174/1566524019666190308122108.

DOI:10.2174/1566524019666190308122108

PMID:30854965

Abstract

PURPOSE

Breast cancer is the most prevalent malignancy and the leading cause of death among women. Triple-negative breast cancer (TNBC) is a subtype of breast cancer and shows a distinctly aggressive nature with higher rates of relapse and shorter overall survival in the metastatic setting compared to other subtypes of breast cancer. This study aimed to assess the effect of KIF15 on various clinicopathological characteristics, survival analysis, and cell proliferation in triple-negative breast cancer, which has not been reported to our knowledge.

METHODS

A total of 165 patients with triple-negative breast cancer were enrolled and clinical data were obtained, Mann-Whitney U analysis was performed to assess the correlation between the expression of KIF15 and clinical pathological characteristics of TNBC patients. Survival analysis was performed by Kaplan-Meier analysis and Log-rank test. The expression levels of KIF15 in cancer tissues and adjacent tissues were evaluated via Sign test. Lentivirus was used to down-regulate the expression of KIF15 in TNBC cells. The cell proliferation, colony formation capacity and apoptosis were examined by MTT, Giemsa staining and flow cytometry assay, respectively.

RESULTS

Our results showed that, among the 165 TNBC patients, the expression of KIF15 was positive correlation with clinicopathological features of TNBC. In addition, KIF15 low-expression group showed higher disease-free survival than KIF15 highexpression group and univariate analysis showed that KIF15 high-expression group appeared higher mortality than KIF low-expression group (P ≤ 0.05). Meanwhile, the expression levels of KIF15 in cancer tissue notably up-regulated in comparison with adjacent tissue. In vitro, knockdown of KIF15 significantly promoted cell apoptosis and suppressed cell proliferation and colony formation of TNBC cells.

CONCLUSION

By utilizing survival analysis, we found that high-expression of KIF15 in the TNBC samples were associated with poorer overall survival, while the anti-tumor effect of KIF15 knockdown was also confirmed at the cellular level in vitro. Taken together, KIF15 can be applied as a potential diagnostic and therapeutic target in TNBC.

摘要

目的

乳腺癌是最常见的恶性肿瘤，也是女性死亡的主要原因。三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，与其他乳腺癌亚型相比，其具有明显的侵袭性，复发率更高，转移性疾病患者的总生存率更短。本研究旨在评估 KIF15 在三阴性乳腺癌中的各种临床病理特征、生存分析和细胞增殖中的作用，据我们所知，这在以前的研究中尚未报道过。

方法

共纳入 165 例三阴性乳腺癌患者，获取临床资料，采用 Mann-Whitney U 分析评估 KIF15 表达与 TNBC 患者临床病理特征的相关性。采用 Kaplan-Meier 分析和 Log-rank 检验进行生存分析。采用 Sign 检验评估癌组织和癌旁组织中 KIF15 的表达水平。利用慢病毒下调 TNBC 细胞中 KIF15 的表达。通过 MTT、吉姆萨染色和流式细胞术分别检测细胞增殖、集落形成能力和细胞凋亡。

结果

结果显示，在 165 例 TNBC 患者中，KIF15 的表达与 TNBC 的临床病理特征呈正相关。此外，KIF15 低表达组的无病生存率高于 KIF15 高表达组，单因素分析显示 KIF15 高表达组的死亡率高于 KIF 低表达组（P≤0.05）。同时，与癌旁组织相比，癌组织中 KIF15 的表达明显上调。在体外，敲低 KIF15 显著促进了 TNBC 细胞的凋亡，抑制了细胞的增殖和集落形成。