Expression and prognostic value of transcription factor forkhead box C1 in triple negative breast cancer

Abstract

Objective To investigate the expression of the transcription factor forkhead box C1 (FOXC1) in triple negative breast cancer (TNBC) and its prognostic value. Methods TNBC patients who received modified radical mastectomy or breast-conserving surgery in the Peking Union Medical College Hospital between March 2002 and March 2012 were retrospectively analyzed in this study. The last follow-up date was March 1, 2019. Archived specimens of primary breast cancer were collected for RNA extraction from those who met the inclusion and exclusion criteria and were recurrence-free for more than 10 years, and those who had an early recurrence or metastasis. RNA extraction was successful in specimens of 59 patients (27 without recurrence or metastasis, and 32 with recurrence or metastasis), excluding those with insufficient specimens or failure in quality control of RNA extraction. The FOXC1 mRNA expression of the specimens was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The χ2 test or nonparametric test (Mann-Witney U test) was used in the comparison of enumeration data and the t test was used in the comparison of age and FOXC1 expression level (ΔCT value) between the recurrent and the non-recurrent groups. Multivariate analysis was performed by the Cox’s proportional hazards regression model. The survival rate was compared by the log-rank test. Results There was no significant difference in age, tumor size, histological grade, P53 status, Ki67 expression and peritumoral vascular invasion between the recurrent and non-recurrent groups (t=-0.226, P=0.165; χ2=1.923, P=0.165; Z=-1.694, P=0.090; χ2=0.336, P=0.562; P=1.000; P=1.000). However, the rate of lymph node metastasis was higher in the recurrent group than in the non-recurrent group[75.0% (24/32) vs 40.7% (11/27), χ2=7.123, P=0.008]. The expression level of FOXC1 in the recurrent group was 2.7 times as high as that in the non-recurrent group (ΔCT value: 4.064±1.392 vs 5.510±1.581, t=3.737, P<0.001). Multivariate analysis showed that high FOXC1 expression was an independent risk factor of recurrence-free survival (RFS) in TNBC patients (HR=2.531, 95%CI: 1.211-5.290, P=0.014). The traditional pathological factors, except lymph node status (HR=2.453, 95%CI: 1.093-5.504, P=0.030), did not reach significant difference to predict recurrence and metastasis. The patients with high expression of FOXC1 had worse RFS and OS (RFS: χ2=8.419, P=0.004; OS: χ2=4.644, P=0.031). Conclusion Patients with high expression of FOXC1 are at increased risk of recurrence and metastasis, so FOXC1 can be used as a candidate prognostic marker for TNBC patients. Key words: Transcription factors; Breast neoplasms; Prognosis