ERCC1/NGFR affects prognosis in basal-like breast cancer.

OBJECTIVES

To study the effects of ERCC1 and NGFR on metastasis and prognosis of basal-like breast cancer, and construct a prognostic prediction model, initially to explore whether ERCC1 plays a role in BLBC metastasis through NGFR.

METHODS

RNA-seq was used to identify the metastasis-related gene NGFR associated with ERCC1. ERCC1 and NGFR were transfected into BLBC cells, then western blot and transwell assays were applied to explore the effects of ERCC1 and NGFR on the migratory/invasive abilities and whether ERCC1 plays a role in BLBC cell metastasis through the NGFR. Data from the TCGA database were used to analyze the relationship between NGFR and ERCC1 expression in BLBC patients. The effects of ERCC1 and NGFR on the prognosis were analysed using K-M survival curves and multifactorial Cox regression, and a prognostic prediction model was constructed.

RESULTS

RNA-seq results showed that NGFR was a differentially expressed gene of ERCC1, and NGFR was associated with ERCC1.After knockdown of ERCC1, the migratory and invasive abilities of cancer cells were significantly reduced; after overexpression of NGFR, the migratory and invasive abilities of cancer cells were significantly enhanced. In ERCC1 knockdown cancer cells, the expression levels of NGFR were subsequently reduced, and overexpression of NGFR resulted in an increase in migrating and invading cells and a rebound in migration and invasion capacity. NGFR was positively correlated with ERCC1 expression levels in BLBC patients (r = 0.24, P < 0.05). The overall survival of patients in the group with high expression of ERCC1 and NGFR was shorter. High expression of ERCC1 (HR = 2.310, 95% CI 1.008 ~ 5.293) and NGFR (HR = 2.600, 95% CI 1.126 ~ 6.002) were independent risk factor for poor outcome. The prognostic prediction model's C-index was 0.781, and the AUC values of 3-year and 5-year survival were 0.76, 0.81, and the calibration curves for 3-year and 5-year survival were close to the reference line. The accuracy of the model was similarly validated in the METABRIC dataset.

CONCLUSIONS

A positive correlation was observed between ERCC1 and NGFR. ERCC1 may affect the migration and invasion ability of BLBC cells through NGFR; ERCC1 and NGFR were independent risk factors for the poor prognosis of BLBC patients and had a predictive effect on the 3-year and 5-year prognosis of BLBC.