Prognostic and tumor-immune infiltration cell signatures in tamoxifen-resistant breast cancers

Zhenyu Cao; Ziwei Jin; Liyun Zeng; Hongye He; Qitong Chen; Qiongyan Zou; Dengjie Ouyang; Na Luo; Yulong Zhang; Yunchang Yuan; Wenjun Yi

doi:10.21037/gs-21-566

Prognostic and tumor-immune infiltration cell signatures in tamoxifen-resistant breast cancers

Gland Surg. 2021 Sep;10(9):2766-2779. doi: 10.21037/gs-21-566.

Authors

Affiliations

¹ Department of General Surgery, the Second Xiangya Hospital of Central South University, Changsha, China.
² Department of Glandular Surgery, Baise People's Hospital, Baise, China.
³ Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University, Changsha, China.

Abstract

Background: The cumulative risk of distant recurrence of hormone receptor-positive (HR+) breast cancer in the past 20 years has ranged from 22% to 52% after 5 years of endo-therapy. The TNM stage, histological grade, and age are important clinical factors related to recurrence, however the exact mechanism of tamoxifen resistance is still unclear.

Methods: Differentially expressed genes (DEGs) were identified in 10 pairs of patients who had relapsed and non-relapsed after tamoxifen treatment based on matching their clinicopathological factors. After analysis of the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 10 hub genes were identified using Cytoscape software. Next, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used to verify the expression and overall survival (OS) of the 10 hub genes respectively, and GSE96058 and Kaplan-Meier Plotter website were used to further verify the OS of C3, CX3CL1, CXCL2, and SAA1. Finally, Immune Cell Abundance Identifier (ImmuCellAI) and the TIMER database were used to estimate immune cell infiltration and the expression of prognostic genes.

Results: The DEGs were mainly enriched in the inflammatory response and cytokine-receptor interaction. The expression and the survival analysis identified CX3CL1, CXCL2, and SAA1 as prognostic factors, whose overexpression in HR+/human epidermal growth factor receptor 2 (HER-2) negative breast cancer possibly predicted a longer disease-free survival. The expression levels of these 3 genes are positively correlated with immune cell infiltration. Their high expression levels may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be biomarkers for tamoxifen-resistant therapy.

Conclusions: In conclusion, the high expression of CX3CL1, CXCL2, and SAA1 may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be a biomarker for tamoxifen therapy.

Keywords: Tamoxifen; The Cancer Genome Atlas (TCGA); breast cancer; immune; resistance.