Abstract
BackgroundThe 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.MethodslncRNA 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.ResultsThree 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.ConclusionThese 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.
Highlights
Several targeted agents are implicated in the therapy of breast cancer (BC), traditional cytotoxic chemotherapy remains a mainstay of treatment
We demonstrated the BC032585, one of the three long noncoding RNA (lncRNA), was directly linked to BC cell sensitivity to chemotherapy. These results suggest that a simple three-lncRNA signature may effectively serve as a predictive biomarker for Pathological complete response (pCR) to neoadjuvant chemotherapy in breast cancer
A Three-LncRNA Signature Is Identified to Be Associated With pCR in BC Patients
Summary
Several targeted agents are implicated in the therapy of breast cancer (BC), traditional cytotoxic chemotherapy remains a mainstay of treatment (von Minckwitz and Martin, 2012; Untch et al, 2014). Pathological complete response (pCR), defined as the complete disappearance of invasive tumor cells in breast and axillary lymph nodes, to neoadjuvant therapy is an effective predictor of tumor progression (Hatzis et al, 2011; von Minckwitz and Martin, 2012), and patients whose tumors show pCR have a better clinical outcome compared to those with residual disease (RD) in the tumor (Bonadonna et al, 1998; Symmans et al, 2007; Rastogi et al, 2008). The purpose of this study is to develop an effective but concise long noncoding RNA (lncRNA) expression signature that can predict response to neoadjuvant chemotherapy for breast cancer (BC) patients
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