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. 2019 Mar 25:12:2171-2180.
doi: 10.2147/OTT.S185662. eCollection 2019.

The role of IRAK1 in breast cancer patients treated with neoadjuvant chemotherapy

Muwen Yang  1 , Xingsong Qin  1 , Guangyuan Qin  2 , Xinyu Zheng  1   2
Affiliations

The role of IRAK1 in breast cancer patients treated with neoadjuvant chemotherapy

Muwen Yang et al. Onco Targets Ther. .

Erratum in

Abstract

Background: IRAK1 has been shown to be abnormally expressed in a set of tumors leading to tumorigenesis and progression. IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel. However, the exact role of IRAK1 in neoadjuvant chemotherapy (NCT) for breast cancer remains unclear. The aim of this study was to investigate the relationship between the expression of IRAK1 and the clinicopathological parameters and survival prognosis of breast cancer patients treated with NCT.

Patients and methods: Based on the clinical data and mRNA microarray data from 1,085 breast cancer patients in The Cancer Genome Atlas, the correlation between IRAK1 expression and clinicopathological parameters of breast cancer was analyzed. Immunohistochemistry was performed to evaluate the expression of IRAK1. The Human Protein Atlas and the String database were used to analyze the expression of IRAK1 protein and its interaction with altered neighboring proteins in breast cancer. IRAK1 alteration was analyzed in cBioPortal database. GEO enrichment of IRAK1 was performed using WEB-based Gene SeT AnaLysis Toolkit.

Results: The expression of IRAK1 was significantly downregulated following NCT. The decreased expression of IRAK1 following NCT was positively correlated with reduced tumor size. Finally, survival analysis confirmed that a shorter survival period was correlated to higher expression of IRAK1 both before and after NCT.

Conclusion: These findings advanced our understanding about the expression pattern of IRAK1 in breast cancer, especially in those patients who were treated with NCT, suggesting that IRAK1 could be used as a prognostic indicator, as well as a potential indicator for evaluating NCT efficacy for breast cancer patients.

Keywords: IRAK1; bioinformatics; breast cancer; neoadjuvant chemotherapy; survival.

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Conflict of interest statement

Disclosure We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of the manuscript. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
IRAK1 expression in The Cancer Genome Atlas (TCGA) database and The Human Protein Altas. Notes: (A) IRAK1 was highly expressed in breast cancer tissues compared with normal breast tissues based on TCGA database. (B) IRAK1 expressed in MCF-7 cell line. (C) IRAK1 expressed in breast cancer tissue.
Figure 2
Figure 2
Immunohistochemistry images of IRAK1 expression in matched breast tumor tissues pre- and post-neoadjuvant chemotherapy (NCT). Notes: (A–D) Representative staining images of IRAK1 in matched breast tumor tissues pre- and post-NCT. (A) Strongly stained. (B) Moderately stained. (C) Moderately stained. (D) Negatively stained. Magnification ×400.
Figure 3
Figure 3
The expression of IRAK1 before and after neoadjuvant chemotherapy. Notes: (A) Difference in expression before and after neoadjuvant chemotherapy. (B) Distribution of the values before and after chemotherapy, respectively. (C) Patients whose tumor sizes diminished by <2 cm, showed no change or increased, were defined as group A, while patients whose tumor sizes diminished by >2 cm or those who achieved pathological complete response were defined as group B. The Mann–Whitney U test was used (P=0.019).
Figure 4
Figure 4
ROC curve and survival curve of IRAK1 expression both pre-neoadjuvant chemotherapy (NCT) and post-NCT. Notes: (A) ROC curve of IRAK1 pre-NCT, an AUC value of 0.681 indicated (P=0.008). (B) Kaplan–Meier survival curve of IRAK1 pre-NCT (log rank: P=0.001). (C) ROC curve of IRAK1 post-NCT. An AUC value of 0.794 (P<0.001). (D) Kaplan–Meier survival curve of IRAK1 post-NCT (log rank: P<0.001).
Figure 5
Figure 5
The alteration of IRAK1 and its interaction in altered neighboring genes from the cBioPortal database. Notes: (A) IRAK1 gene alteration. In this cohort, 7% (56/816) of invasive breast cancer cases exhibited IRAK1 gene alteration. (B) Network of IRAK1 and altered neighboring genes. Analysis of the overall survival (C) and disease-free survival (D) of invasive breast cancer patients with and without IRAK1 gene alteration. No statistically significant difference was identified.
Figure 6
Figure 6
IRAK1 protein expression in the String database. Notes: (A) Corresponding proteins of IRAK1 protein in network visualization. (B,C) Pearson correlation analysis revealed that IRAK1 expression was significantly correlated with the expression of IRF7 and MYD88, respectively.
Figure 7
Figure 7
The enrichment results of IRAK1 using web-based Gene SeT AnaLysis Toolkit. Notes: (A) IRAK1 enrichment in biological process, cellular component, and molecular function. (B) Positively related genes of IRAK1. (C) Negatively related genes of IRAK1. (D) Volcano plot of IRAK1 in breast cancer.
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