LncRNA Profile Study Reveals a Three-LncRNA Signature Associated With the Pathological Complete Response Following Neoadjuvant Chemotherapy in Breast Cancer.

Background: The purpose of this study is to develop an effective but concise long non-coding RNA (lncRNA) expression signature that can predict response to neoadjuvant chemotherapy for breast cancer (BC) patients. Methods: lncRNA expression profiling in 1102 BC patients from Gene Expression Omnibus datasets was analyzed using lncRNA-mining approach. The association between lncRNA signature and pathological complete response (pCR) was analyzed using logistic regression model in the training set (GSE25066, n = 488). Validation was performed in independent testing datasets, GSE20194, GSE20271, GSE22093, and GSE23988 (n = 614). Bonferroni method was employed for multiple testing corrections. Cell proliferation assay and Western blot assay were performed to evaluate the cell viability and protein expression level, respectively. Results: Three lncRNAs (AK291479, U79293, and BC032585) have been identified to be significantly associated with pCR in the training dataset (Bonferroni p-value < 0.05). Expression signature with these lncRNAs was predictive of pCR in the training (AUC = 0.74) and testing (AUC = 0.72) datasets. Weighted gene co-expression network analysis and gene functional annotation suggest that the three lncRNAs were involved in cell cycle process. To confirm the functional significance of the identified lncRNAs, BC032585 was selectively silenced using RNA interference. Knockdown of BC032585 lncRNA significantly promoted cell resistance to multiple anticancer-drugs through upregulating MDR1 expression in breast cancer cells. Conclusion: These results suggest that lncRNAs such as BC032585 might be involved in chemotherapeutic response in breast cancer patients, and the three-lncRNA signature identified in the present study may serve as a useful biomarker for the selection of responsive breast cancer patients in neoadjuvant chemotherapy.