Clinical Impact of 11q13.3 Amplification on Immune Cell Infiltration and Prognosis in Breast Cancer
Renyu Zhou, Xiaoxi Zhu, Yulong Peng, Lijuan Zhong, Lilin Peng, Bo Yang, Yuhua Meng, Xuanzhao Chen, Yuanzhi Lu
Abstract
Introduction: Amplification of the 11q13.3 locus has been observed in various tumors. This study sought to determine the correlation of gene amplification at the 11q13.3 locus with the immune status and survival of breast cancer. Methods: Amplification of the 11q13.3 locus was characterized by analyzing a publicly available database from the cBioPortal platform (TCGA). The correlation of amplified genes with immune cell infiltration in breast cancer was further analyzed using the TIMER2.0 platform. Immunohistochemical staining was used to determine the expression levels of Cyclin D1 (CCND1), Fas-associated death domain (FADD) and P53 in 156 clinical breast cancer samples. Results: This study revealed that amplification of the 11q13.3 amplicon in breast cancer is likely more frequently detected in luminal B breast cancer. Moreover, high expression or amplification of CCND1 , fibroblast growth factor 3 ( FGF3 ), fibroblast growth factor 4 ( FGF4 ), fibroblast growth factor 19 ( FGF19 ) and FADD was inversely correlated with the abundance of CD4+ T cells and dendritic cell infiltration in breast cancer ( P < 0.05). Data analysis also demonstrated that high expression of CCND1, FGF4 and FADD mRNA levels was closely correlated with shorter recurrence-free survival (RFS) in patients with breast cancer ( P < 0.05). The results of immunohistochemical staining from clinical samples further confirmed that high expression of CCND1 and FADD was frequently detected in luminal B and high-grade breast cancer with shorter metastasis-free survival times ( P < 0.05). Conclusion: This study demonstrated that coamplification of genes located on the 11q13.3 amplicon is frequently detected in luminal B subtype breast cancer and is closely associated with worse survival in patients with breast cancer. Moreover, coamplification of the CCND1-FGF locus might decrease antitumor immune activity in breast cancer, indicating that coamplification of the 11q13.3 amplicon is likely to be a key determinant of therapeutic resistance and accelerate the aggressive evolution of breast cancer. Keywords: breast cancer, chromosomal amplification, 11q13.3 amplicon, prognosis, immune microenvironment