A nine-lncRNA signature predicts distant relapse-free survival of HER2-negative breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy.

ABSTRACT

Multi-gene prognostic signatures of long non-coding RNAs (lncRNAs) provide new insights into mechanisms of HER2-negative breast cancer development and progression, and predict distant relapse-free survival (DRFS) of patients receiving taxane and anthracycline-based neoadjuvant chemotherapy. The aim of this study was to develop such a multi-lncRNAs signature. Optimal multiple candidate signature lncRNAs associated with DRFS were firstly identified by a univariate Cox proportional hazard regression survival analysis and a robust likelihood-based survival analysis of the GEO dataset GSE25055. A nine-lncRNA prognostic risk score model Risk Score = 0.0289 × EXPLOC100507388 - 0.0814 × EXPLINC00094 - 0.2422 × EXPSMG7-AS1 - 0.2433 × EXPPP14571 + 0.4690 × EXPASAP1-IT1 - 0.2483 × EXPLOC103344931 - 0.2464 × EXPFAM182A + 0.3349 × EXPHCG26 - 0.0216 × EXPLINC00963 was built according to the coefficients of multivariate survival analysis of the association between the candidate lncRNAs and survival. EXPlncRNA was the standardized log2-transformed expression level of the gene. According to this model, higher scores predicted lower survival probability. The area under Receiver operating characteristic (ROC) curve (AUC) was 0.777 to 0.823 from 1- to 7- year survival rate. The model and its individual lncRNAs differentiated survival probability between the higher scores (expression) and the lower scores (expression). The nine-lncRNA signature had the robust prognostic power compared with ER, PR, tumor size (T), lymph node invasion (N), TNM stage, pathologic response, chemosensitivity prediction and PAM50 signature. These results were consistent with those based on the GEO dataset GSE25065. The predictive nomograms integrating both the nine-lncRNA signature classifier and clinical-pathological risk factors were robust in predicting 1-, 3- and 5- year survival probabilities. These results supported that the nine-lncRNA signature was a robust and effective model in predicting DRFS of patients with HER2-negative breast cancer following taxane and anthracycline-based neoadjuvant chemotherapy.