Increased Expression of DNA2 Was Linked to Poor Prognosis in Breast Cancer.

Yingyan Han,Zhi Wang,Zeyu Zhang,Shujuan Sun,Hubertus Himmerich

doi:10.1155/2021/8860728

Abstract

DNA double-strand break (DSB) repaired by homologous recombination (HR) is an essential process for breast cancer cells to survive. DNA2 nuclease acts parallel to homologous recombination (HR). Here, we investigated the detailed clinical attribute of DNA2 in breast cancer and the role of DNA2 in breast cancer cells' growth. We found that elevated expression of DNA2 was obviously linked to poor prognosis in breast cancer. Further, DNA2 expression was increased in the ER-negative group, PR-negative group, HER2-positive group, and high-grade group via analyzing 2,509 breast cancers in “cBioportal” and 3,063 breast cancer data in “bc-GenExMiner.” Besides, the immunohistochemical staining in 26 breast cancer tissues also showed that elevated expression of DNA2 was correlated with ER-/PR-/HER+. To further detect the role of DNA2 in breast cancer cells, we took GESA, GO, and KEGG analyses and found that DNA2 was enriched in cell cycle and DNA replication pathways. Furthermore, silencing of DNA2 inhibited cell growth in T47D and MD-MB-231 breast cancer cells and suppressed tumor growth in vivo, indicating DNA2 functioned importantly in breast cancer progression and maybe a potential prognostic marker in breast cancer. Our research reveals that DNA2 is a biomarker for diagnosis and prognosis in breast cancer from multiple perspectives and gives a new clue for further preclinical and clinical investigation.

Highlights

Despite significant advances in our understanding and management of breast cancer over the past 50 years, the disease remains a serious health problem and a major challenge on a global scale [1, 2]
According to the expression status of three receptors: the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), breast cancer has been classified into Luminal A (LumA), Luminal B (LumB), epidermal growth factor receptor ERBB2/HER2-overexpressing (HER2+), and basal epithelial-like (BL)
The survival curves obtained from the KM plotter suggested that DNA replication helicase/nuclease 2 (DNA2) high expression was correlated to worse overall survival (OS) for all breast cancer patients, hazard ratio ðHRÞ = 1:31ð1:03 − 1:65Þ, p = 0:024 (Figure 1(b))

Summary

Introduction

Despite significant advances in our understanding and management of breast cancer over the past 50 years, the disease remains a serious health problem and a major challenge on a global scale [1, 2]. According to the expression status of three receptors: the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), breast cancer has been classified into Luminal A (LumA), Luminal B (LumB), epidermal growth factor receptor ERBB2/HER2-overexpressing (HER2+), and basal epithelial-like (BL) This can be helpful to predict patient outcomes and provide new choices for treatment [3,4,5]. Treatment options for breast cancer patients consist of surgery, chemotherapy, radiotherapy or targeting of classical markers of breast cancer subtype, and emerging new therapy [5]. These treatments have some limitations, and new studies are needed [3, 6, 7]. These findings improved the understanding of DNA2, providing evidence that DNA2 was a potential biomarker of diagnosis and prognosis in breast cancer

Materials and Methods

Result

Discussion