Development of a risk scoring system for evaluating the prognosis of patients with Her2-positive breast cancer

Chundi Gao; Jing Zhuang; Huayao Li; Cun Liu; Chao Zhou; Lijuan Liu; Fubin Feng; Changgang Sun; Jibiao Wu

doi:10.1186/s12935-020-01175-1

Development of a risk scoring system for evaluating the prognosis of patients with Her2-positive breast cancer

Cancer Cell Int. 2020 Apr 15:20:121. doi: 10.1186/s12935-020-01175-1. eCollection 2020.

Authors

Chundi Gao¹, Jing Zhuang², Huayao Li³, Cun Liu¹, Chao Zhou², Lijuan Liu², Fubin Feng², Changgang Sun⁴, Jibiao Wu³

Affiliations

¹ 1College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014 Shandong People's Republic of China.
² Departmen of Oncology, Weifang Traditional Chinese Hospital, Weifang, 261041 Shandong People's Republic of China.
³ 2College of Basic Medical, Shandong University of Traditional Chinese Medicine, Jinan, 250014 Shandong People's Republic of China.
⁴ 4Cancer and Immunology Institute, Shandong University of Traditional Chinese Medicine, Jinan, Shandong People's Republic of China.

Abstract

Background: As one of the many breast cancer subtypes, human epidermal growth factor receptor 2 (Her2)-positive breast cancer has higher invasiveness and poor prognosis, although the advent of anti-Her2 drugs has brought good news to patients. However, the emergence of drug resistance still limits its clinical efficacy, so there is an urgent need to explore new targets and develop a risk scoring system to improve treatments and evaluate patient prognosis.

Methods: Differentially expressed mRNAs associated with Her2-positive breast cancer were screened from a TCGA cohort. The prognostic risk scoring system was constructed according to univariate and Lasso Cox regression model analyses and combined with clinical factors (such as age and TNM) for univariate and multivariate analyses to verify the specificity and sensitivity of the risk scoring system. Finally, based on correlation and CNV mutation analyses, we explored the research value of the mRNAs involved in the system as key genes of the model.

Results: In this study, six mRNAs were screened and identified to construct a prognostic risk scoring system, including four up-regulated mRNA (RDH16, SPC25, SPC24, and SCUBE3) and two down-regulated mRNA (DGAT2 and CCDC69). The risk scoring system can divide Her2-positive breast cancer samples into high-risk and low-risk groups to evaluate patient prognosis. In addition, whether through the time-dependent receiver operating characteristics curve or compared with clinical factors, the risk scoring system showed high predictive sensitivity and specificity. Moreover, some CNV mutations in mRNA increase patient risk by influencing expression levels.

Conclusion: The risk scoring system constructed in this study is helpful to improve the screening of high-risk patients with Her2-positive breast cancer and is beneficial for implementing early diagnosis and personalized treatment. It is suggested that these mRNAs may play an important role in the progression of Her2-positive breast cancer.

Keywords: Copy number variation; Her2-positive breast cancer; Lasso Cox regression analysis; Prognostic risk scoring system; Survival analysis.