Network-based approach to identify biomarkers predicting response and prognosis for HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy

PeerJ

article

Cui Jiang¹  Shuo Wu¹  Lei Jiang¹  Zhichao Gao¹  Xiaorui Li¹  Yangyang Duan¹  Na Li²  Tao Sun¹ 

[1] Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute;Institute of Translational Medicine, China Medical University

关键词: Response;    Breast cancer;    Neoadjuvant chemotherapy;    Prognosis;    WGCNA;   

DOI  :  10.7717/peerj.7515

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

ObjectiveThis study aims to identify effective gene networks and biomarkers to predict response and prognosis for HER2-negative breast cancer patients who received sequential taxane-anthracycline neoadjuvant chemotherapy.Materials and MethodsTranscriptome data of training dataset including 310 HER2-negative breast cancer who received taxane-anthracycline treatment and an independent validation set with 198 samples were analyzed by weighted gene co-expression network analysis (WGCNA) approach in R language. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were performed for the selected genes. Module-clinical trait relationships were analyzed to explore the genes and pathways that associated with clinicopathological parameters. Log-rank tests and COX regression were used to identify the prognosis-related genes.ResultsWe found a significant correlation of an expression module with distant relapse–free survival (HR = 0.213, 95% CI [0.131–0.347], P = 4.80E−9). This blue module contained genes enriched in biological process of hormone levels regulation, reproductive system, response to estradiol, cell growth and mammary gland development as well as pathways including estrogen, apelin, cAMP, the PPAR signaling pathway and fatty acid metabolism. From this module, we further screened and validated six hub genes (CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2), the expression of which were significantly associated with both better chemotherapeutic response and favorable survival for BC patients.ConclusionWe used WGCNA approach to reveal a gene network that regulate HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy, which enriched in pathways of estrogen signaling, apelin signaling, cAMP signaling, the PPAR signaling pathway and fatty acid metabolism. In addition, genes of CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2 might serve as novel biomarkers predicting chemotherapeutic response and prognosis for HER2-negative breast cancer.

【 授权许可】

CC BY