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SKA3的过表达与女性早期乳腺癌的不良预后相关。

Overexpression of SKA3 correlates with poor prognosis in female early breast cancer.

作者信息

Zhong Yue, Zhuang Zhenjie, Mo Peiju, Lin Mandi, Gong Jiaqian, Huang Jiarong, Mo Haiyan, Lu Yuyun, Huang Mei

机构信息

Guangzhou University of Chinese Medicine, Guangzhou, China.

College of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

PeerJ. 2021 Dec 13;9:e12506. doi: 10.7717/peerj.12506. eCollection 2021.

Abstract

BACKGROUND

Spindle and kinetochore associated complex subunit 3 (SKA3) plays an important role in tumorigenesis and the progression of various tumors. But the relationship between SKA3 and early breast cancer remains unclear. The study aimed to explore the prognostic significance of SKA3 in breast cancer.

METHODS

In the study, SKA3 expression was initially assessed using the Oncomine database and The Cancer Genome Atlas database (TCGA). Then, we presented validation results for RT-qPCR (quantitative reverse transcription PCR) and ELISA (enzyme-linked immunosorbent assay). The relationship between clinical characteristics and SKA3 expression was assessed by Chi-square test and Fisher's exact test. Kaplan-Meier method and Cox regression analysis were conducted to evaluate the prognostic value of SKA3. Gene set enrichment analysis (GSEA) was performed to screen biological pathways using the TCGA dataset. Besides, single sample gene set enrichment analysis (ssGSEA) was utilized to identify immune infiltration cells about SKA3.

RESULTS

SKA3 mRNA was expressed at high levels in breast cancer tissues compared with normal tissues. Chi-square test and Fisher's exact test showed SKA3 expression was related to age, tumor (T) classification, node (N) classification, tumor-node-metastasis (TNM) stage, estrogen receptor (ER), progesterone receptor (PR), molecular subtype, and race. RT-qPCR results showed that SKA3 expression was overexpressed in ER, PR status, and molecular subtype in Chinese people. Kaplan-Meier curves implicated that high SKA3 expression was related to a poor prognosis in female early breast cancer patients. Cox regression models showed that high SKA3 expression could be used as an independent risk factor for female early breast cancer. Four signaling pathways were enriched in the high SKA3 expression group, including mTORC1 signaling pathway, MYC targets v1, mitotic spindle, estrogen response early. Besides, the SKA3 expression level was associate with infiltrating levels of activated CD4 T cells and eosinophils in breast cancer.

CONCLUSION

High SKA3 expression correlates with poor prognosis and immune infiltrates in breast cancer. SKA3 may become a biomarker for the prognosis of breast cancer.

摘要

背景

纺锤体和动粒相关复合体亚基3(SKA3)在各种肿瘤的发生和发展中起重要作用。但SKA3与早期乳腺癌之间的关系仍不清楚。本研究旨在探讨SKA3在乳腺癌中的预后意义。

方法

在本研究中,首先使用Oncomine数据库和癌症基因组图谱数据库(TCGA)评估SKA3的表达。然后,我们展示了逆转录定量聚合酶链反应(RT-qPCR)和酶联免疫吸附测定(ELISA)的验证结果。通过卡方检验和Fisher精确检验评估临床特征与SKA3表达之间的关系。采用Kaplan-Meier法和Cox回归分析评估SKA3的预后价值。利用TCGA数据集进行基因集富集分析(GSEA)以筛选生物学通路。此外,采用单样本基因集富集分析(ssGSEA)来识别与SKA3相关的免疫浸润细胞。

结果

与正常组织相比,SKA3 mRNA在乳腺癌组织中高表达。卡方检验和Fisher精确检验显示SKA3表达与年龄、肿瘤(T)分级、淋巴结(N)分级、肿瘤-淋巴结-转移(TNM)分期、雌激素受体(ER)、孕激素受体(PR)、分子亚型和种族有关。RT-qPCR结果显示,在中国人群中,SKA3在ER、PR状态和分子亚型中表达上调。Kaplan-Meier曲线表明,SKA3高表达与女性早期乳腺癌患者的不良预后相关。Cox回归模型显示,SKA3高表达可作为女性早期乳腺癌的独立危险因素。在SKA3高表达组中富集了四条信号通路,包括mTORC1信号通路、MYC靶标v1、有丝分裂纺锤体、早期雌激素反应。此外,SKA3表达水平与乳腺癌中活化CD4 T细胞和嗜酸性粒细胞的浸润水平相关。

结论

SKA3高表达与乳腺癌的不良预后和免疫浸润相关。SKA3可能成为乳腺癌预后的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b164/8675262/edd654f7d7f7/peerj-09-12506-g001.jpg

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