探讨转录因子叉头框C1(FOXC1)在三阴性乳腺癌(TNBC)中的表达及其与患者预后的关系。

回顾性分析2002年3月至2012年3月在中国医学科学院北京协和医学院北京协和医院进行乳腺癌改良根治术或保留乳房手术的TNBC患者临床资料。患者随访截止日期为2019年3月1日。选择符合纳入、排除标准且有复发、转移或随访10年以上无复发、转移的患者，提取乳腺癌原发灶组织RNA进行分析。排除标本不足或RNA提取质控不达标的患者后，最终有59例(27例无复发、转移，32例复发、转移)标本通过定量反转录聚合酶链反应(qRT-PCR)检测FOXC1表达量。患者临床特征的分析采用χ²检验或非参数检验(Mann-Witney U检验)；复发、转移组与无复发、转移组患者年龄及FOXC1表达量(ΔCT值)的比较采用t检验；多因素分析采用Cox比例风险回归模型；患者生存率的比较采用log-rank检验。

复发、转移组与无复发、转移组患者比较，年龄、肿瘤大小、组织学分级、P53、Ki67表达和脉管癌栓的差异均无统计学意义(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)，但复发、转移组患者腋窝淋巴结转移的比例更高[75.0% (24/32)比40.7% (11/27)，χ²＝7.123，P＝0.008]。复发、转移组FOXC1表达量是无复发、转移组的2.7倍，2组比较，差异有统计学意义(ΔCT值：4.064±1.392比5.510±1.581，t＝3.737，P<0.001)。多因素分析提示，FOXC1高表达是TNBC患者无复发生存(RFS)的独立危险因素(HR＝2.531，95%CI：1.211～5.290，P＝0.014)，而临床上常用的病理指标，仅淋巴结转移与RFS相关(HR＝2.453，95%CI：1.093～5.504，P＝0.030)。FOXC1高表达的TNBC患者，其RFS和OS都更差(RFS：χ²＝8.419，P＝0.004；OS：χ²＝4.644，P＝0.031)。

FOXC1高表达患者出现复发、转移的风险显著增加，可以作为TNBC预后细分的有用指标。

To investigate the expression of the transcription factor forkhead box C1 (FOXC1) in triple negative breast cancer (TNBC) and its prognostic value.

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.

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).

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.