Purpose: The long non-coding RNA H19, a conservatively imprinted gene, acts as a molecular sponge for the let-7 family, which has been identified as a set of tumor suppressors. However, the combined prognostic value of H19 and let-7a signature in breast cancer patients remains unclear.
Methods: In this research we assessed the prognostic value of the combined H19 and let-7a signature in breast cancer patients by retrospectively reviewing that data of 79 patients who underwent neoadjuvant chemotherapy; we also investigated the expression and function of H19 in breast cancer cell lines in vitro. Survival data were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression method. As determined using X-tile, the optimal cutoff value for the risk score to assess progression-free survival (PFS) based on the combined signature was -0.1.
Results: Patients with an overall positive treatment response had higher let-7a and lower H19 levels. In addition, let-7a expression was negatively correlated with H19 expression. Patients with a risk score of >-0.1 had shorter overall survival and PFS. In vitro data showed that chemoresistant cell lines exhibit higher H19 and lower let-7a levels and knockdown H19 restores paclitaxel sensitivity.
Conclusion: Our results suggest that the combined let-7a and H19 signature is a novel prognostic factor for breast cancer patients treated with neoadjuvant chemotherapy.
Keywords: Breast neoplasms; H19 long non-coding RNA; Hsa-let-7a-1 microRNA; Neoadjuvant therapy; Prognosis.