Abstract P5-07-07: Prognostic relevance of microRNA-155 and microRNA-21 in breast cancer patients
Authors: Kim SY , Kawaguchi T , Yan L , Young J , Qi Q , Takabe K 
Published: February 2018

Introduction

MicroRNAs (miRNAs) are short noncoding RNA sequences that degrade or prevent the translation of their target messenger RNA (mRNA). Altered regulation of miRNAs is implicated in different cellular processes. Some miRNAs, such as miRNA-155 (miR155) and miRNA-21 (miR21), are implicated in both immunity and cancer progression. Previous studies show that both miR155 and -21 are oncogenic, as their overexpression promotes invasion, proliferation and migration of breast cancer cells in vitro. Their overexpression within patient cohorts (n= 40-173 patients) reveals a worse prognosis for miR21 and varying associations with prognosis for miR155. By using the Cancer Genome Atlas (TCGA), which contains data from over a thousand patients, we want to clarify whether high expression of miR155 or -21 is associated with an improved or worse survival within breast tumor samples. Because both miR155 and -21 are described as oncogenic, we hypothesize that high expression of these miRNAs would portend a worse survival.

Methods

Within the breast cohort, 1052/1097 patients within TCGA contained both clinical and miRNA sequence data, acquired via the Genomic Data Common (GDC) data portal. The patients were separated into a high and low expression group for both miR155 and miR21, and associations with overall survival were obtained using the Cox proportional hazard model. Furthermore, a sub-analysis was conducted based on estrogen, progesterone and Her-2 receptor status (ER, PR, Her-2) as well as TNM staging (AJCC 7th edition).

Results

General patient characteristics within the breast cancer cohort of TCGA included: 70% Caucasian, 73% &gt;50 years old, 75% with TNM stage I and II breast cancers, 74% ER positive, and 33% Her-2 positive. We unexpectedly found that miR155 and miR21 high expression was associated with an improved survival (p=0.05 and 0.038 respectively). In the sub-analysis, a positive association with survival was seen for miR155 high expression in ER negative, and Stage I-II breast cancers (p=0.025, 0.0013 respectively), but not in Stage III-IV. The sub-analysis for miR21 found an association with improved survival for miR21 high expression in ER negative, and stage I-II patients (p=0.033, 0.0015 respectively), but not in Stage III-IV. Although not statistically significant, a trend towards improved survival was found in ER and PR positive subgroups, for both miR155 and -21. For the Her-2 negative subgroup, there was a trend for improved survival in miR155 high expression, but not in miR21 high expression. Knowing that ER negative tumors can attract more immune cells, and that miR155 and -21 can be expressed in immune cells and tumor associated fibroblasts respectively, we speculate that their high expression was concentrated within cells from the tumor microenvironment rather than the cancer cells.

Conclusion

Using TCGA as a large validation cohort, we found that high expression of miR155 and miR21 was associated with an improved survival, which was contrary to what we predicted. Future experiments using computational biology to determine the cell type composition within the TCGA tumor samples will be performed in an effort to determine whether the tumor microenvironment influenced the survival patterns we observed in the high expression groups of miR155 and -21.

Citation Format: Kim SY, Kawaguchi T, Yan L, Young J, Qi Q, Takabe K. Prognostic relevance of microRNA-155 and microRNA-21 in breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-07.