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

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.

Alterations of Lipid Metabolism in Cancer: Implications in Prognosis and Treatment

“…Two human DGAT isoforms have been described (182). The expression of DGAT2 in HER2-positive breast cancer was decreased and was closely related to patient prognosis (140). However, data from TCGA reported DGAT2 as an unfavorable prognostic factor for endometrial cancer ( Table 1).…”

Identification and development of an independent immune-related genes prognostic model for breast cancer

“…Wang et al [ 31 ] identified a six differentially-expressed genes (DEGs) model consisting of IGHA2, SERPINA1, GFALS, SPDYC, PAX7, and ADRB1 by using Cox regression survival modeling for breast cancer. In another study [ 32 ], the authors constructed a prognostic risk scoring system containing 6 genes (SCUBE3, RDH16, SPC24, SPC25, CCDC69 and DGAT2), suggesting that these mRNAs may serve a driving role in the progression of Her2-positive BC. The construction of this risk scoring system is conducive to identifying high-risk HER2-positive BC patients, and it subserve to help achieve personalized targeted therapy.…”

Study on <em>CCDC69</em> interfering with the prognosis of patients with breast cancer through PPAR signal pathway

“…The univariate analysis shows that CCDC69 is a low-risk factor for breast cancer. 17 It can be seen that the high expression of CCDC69 is a protective factor for the prognosis of breast cancer patients.…”