Significance of Oncotype DX 21-Gene Test and Expression of Long Non-Coding RNA MALAT1 in Early and Estrogen Receptor-Positive Breast Cancer Patients

Abstract

Objective: To investigate the association between the recurrence score (RS) obtained by Oncotype DX 21-gene test and long non-coding RNA (lncRNA) MALAT1 expression in early and estrogen receptor-positive (ER⁺) breast cancer.

Materials and methods: The Oncotype DX 21-gene test and MALAT1 expression detection were performed in tumor samples from 76 ER⁺ and early breast cancer patients with the Surplex liquid chip. The RS value was calculated based on the expression of total 21 genes. The level of MALAT1 was measured in both tumor tissue and para-tumor tissue, and relatively quantified with an internal control gene. Mann-Whitney U-test or Kruskal-Wallis test were used to analyze the association between MALAT1 level and different clinical pathological characteristics, including age, tumor stage, disease grade, lymph node status, Ki-67 expression, and progesterone receptor (PR) status. The association between the RS and different characteristics was analyzed by Wilcoxon rank-sum test. Correlation between two parameters was analyzed by Spearman's rank correlation analysis.

Results: The expression of MALAT1 was more abundant in tumor tissue (2.992 ± 2.256) than that in adjacent normal tissue (1.641±1.438, Z=-2.594, p=0.009), and it was not correlated with any clinical pathological characteristics. According to the old criteria for RS stratification, 52.7% of patients were in low risk (RS<18), 36.8% of patients were in medium risk (18≤RS≤30), and 10.5% of patients were in high risk (RS>30). While under the new criteria, 18.4% were in low risk group (RS<11), 63.2% were in a medium risk group (11≤RS≤26), and 18.4% were in a high risk group (RS>26). The Oncotype DX 21-gene results only correlated with Ki-67 expression under both new and old criteria, and it was not related with other cancer characteristics. The expression of lncRNA MALAT1 was significantly correlated with the Oncotype DX 21-gene results under the old criteria.

Conclusion: MALAT1 is a novel breast cancer biomarker independent of tumor stage, disease grade and lymph node status. MALAT1 level is associated with the Oncotype DX 21-gene RS value. Therefore, combination of MALAT1 and the Oncotype DX 21-gene test may be used to predict prognosis in ER⁺ and early stage breast cancer.

Keywords: MALAT1; Oncotype DX 21-gene test; breast cancer; long non-coding RNA; lncRNA; risk of recurrence.