摘要
Background: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. Methods: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). Results: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. Conclusions: A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
基金
supported by the National Key Research and Development Program of China(2019YFE0110000)
National Natural Science Foundation of China(82072097)
CAMS Innovation Fund for Medical Science(CIFMS)(2020-I2M-C&T-B-069,2021-I2M-1-014)
and Beijing Hope Run Special Fund of Cancer Foundation of China(LC2020A18).
作者简介
Jiaxiang Liu and Shuangtao Zhao contributed equally to this work;Shuangtao Zhao,Jiaxiang Liu contributed equally to this work;Correspondence to:Xin Wang,Department of Breast Surgical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,No.17 Panjiayuan Nanli,Chaoyang District,Beijing 100021,China,E-Mail:xinwang@vip.126.com;Correspondence to:Jianming Ying,Department of Pathology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,No.17 Panjiayuan Nanli,Chaoyang District,Beijing 100021,China,E-Mail:jmying@cicams.ac.cn;Correspondence to:Yueping Liu,Department of Pathology,The Fourth Hospital of Hebei Medical University,No.12 Jiankang Road,Shijiazhuang,Hebei 050011,China,E-Mail:annama@163.com
