Prognostic value of using glucosylceramide synthase and cytochrome P450 family 1 subfamily A1 expression levels for patients with triple-negative breast cancer following neoadjuvant chemotherapy

Neoadjuvant chemotherapy (NACT) has been considered to be the preferred treatment option for early operable triple-negative breast cancer (TNBC). However, resistance to drugs remains to be the barrier to the efficacy of NACT. Glucosylceramide synthase (GCS) and cytochrome P450 family 1 subfamily A1 (CYP1A1) have been previously associated with drug resistance in breast cancer. The present study aimed to explore whether the expression levels of GCS and/or CYP1A1 are associated with the prognosis of TNBC after NACT. Immunohistochemistry was used to detect and measure GCS and CYP1A1 expression. Associations between GCS or CYP1A1 expression and the clinicopathological characteristics, pathological complete response (pCR), clinical complete response (cCR) and disease-free survival (DFS) were analyzed. GCS expression was found to be associated with tumor size (P=0.021) and TNM staging (P=0.042), whilst CYP1A1 expression was associated with lymph node metastasis (P = 0.026) and TNM staging (P=0.034). The expression levels of GCS (P=0.024) and CYP1A1 (P=0.027) were upregulated after NACT. GCS and CYP1A1 expression were positively correlated (P=0.003; r=0.327). No difference was observed between the GCS⁺ (P=0.188) or CYP1A1⁺ group (P=0.073) and the GCS^- or CYP1A1^- group in terms of pCR. However, compared with that in the GCS⁺CYP1A1⁺ group, the pCR was markedly increased in the GCS^-CYP1A1^- group (P=0.031). The cCR was lower in the GCS⁺ (P=0.021) and CYP1A1⁺ groups (P=0.016) compared with in the GCS^- or CYP1A1^- group. The DFS rate (57.9 vs. 65.4%; P=0.049) was lower in the GCS⁺CYP1A1⁺ group compared with that in the GCS^-CYP1A1^- group. However, there was no statistical significance after P-value was adjusted for multiple comparisons using Bonferroni correction. In conclusion, co-expression of GCS and CYP1A1 was associated with pCR and DFS in TNBC, which may serve a role in the prediction of the prognosis of patients with TNBC following treatment with NACT.