Potential Prognostic Biomarkers of NIMA (Never in Mitosis, Gene A)-Related Kinase (NEK) Family Members in Breast Cancer.

Gangga Anuraga,Nam Nhut Phan,Chih-Yang Wang,Do Thi Minh Xuan,Nu Thuy An Ton,Wei-Jan Wang,Vivin Andriani,Yung-Fu Wu,Fidelia Berenice Prayugo,Kuen-Haur Lee,Muhammad Athoillah,Hoang Dang Khoa Ta,Su-Chi Ku

doi:10.3390/jpm11111089

Abstract

Breast cancer remains the most common malignant cancer in women, with a staggering incidence of two million cases annually worldwide; therefore, it is crucial to explore novel biomarkers to assess the diagnosis and prognosis of breast cancer patients. NIMA-related kinase (NEK) protein kinase contains 11 family members named NEK1-NEK11, which were discovered from Aspergillus Nidulans; however, the role of NEK family genes for tumor development remains unclear and requires additional study. In the present study, we investigate the prognosis relationships of NEK family genes for breast cancer development, as well as the gene expression signature via the bioinformatics approach. The results of several integrative analyses revealed that most of the NEK family genes are overexpressed in breast cancer. Among these family genes, NEK2/6/8 overexpression had poor prognostic significance in distant metastasis-free survival (DMFS) in breast cancer patients. Meanwhile, NEK2/6 had the highest level of DNA methylation, and the functional enrichment analysis from MetaCore and Gene Set Enrichment Analysis (GSEA) suggested that NEK2 was associated with the cell cycle, G2M checkpoint, DNA repair, E2F, MYC, MTORC1, and interferon-related signaling. Moreover, Tumor Immune Estimation Resource (TIMER) results showed that the transcriptional levels of NEK2 were positively correlated with immune infiltration of B cells and CD4+ T Cell. Collectively, the current study indicated that NEK family genes, especially NEK2 which is involved in immune infiltration, and may serve as prognosis biomarkers for breast cancer progression.

Highlights

Breast cancer is one of the most common cancers that frequently occurs in women.it has become one of the significant causes of death in women throughout the world
We found a significant result in the survival analysis, which revealed that NEK2/6/8 had high homologous repair (HR) and overexpression prognostic significance in distant metastasis-free survival (DMFS) in breast cancer patients
We found a significant result in the survival analysis, which revealed that NEK2/6/8 have high HRs and overexpression prognostic significance in DMFS in breast cancer patients

Summary

Introduction

Breast cancer is one of the most common cancers that frequently occurs in women. It has become one of the significant causes of death in women throughout the world. The complexity of breast cancer makes it difficult to fully comprehend its carcinogenesis, progression, invasion, and metastasis using clinical and molecular markers used for early detection [2,3,4,5,6]. NIMA (Never in Mitosis, Gene a)-Related Kinase (NEK) is a family of protein kinases [13]. NEK consists of 11 members of protein kinase, namely NEK1~NEK11 [14,15]

Methods

Results

Conclusion