Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Breast Cancer Res Treat. 2020 Nov;184(2):325-334. doi: 10.1007/s10549-020-05874-1. Epub 2020 Aug 18.
We investigated the expression profiles of immune genes in patients with triple-negative breast cancer (TNBC) to identify the prognostic value of immune genes and their clinical implications.
NanoString nCounter Analysis of 770 immune-related genes was used to measure immune gene expression in patients with TNBC who underwent curative surgery followed by adjuvant chemotherapy at Samsung Medical Center between 2000 and 2004. Statistical analyses were conducted to identify the associations between gene expression and distant recurrence-free survival (DRFS).
Of 1189 patients who underwent curative BC surgery, 200 TNBC patients were included and stage was the only clinical factor predictive of DRFS. In terms of immune genes, 155 of 770 genes were associated with DRFS (p < 0.01). Further multivariate analysis revealed that 13 genes, CD1B, CD53, CT45A1, GTF3C1, IL11RA, IL1RN, LRRN3, MAPK1, NEFL, PRKCE, PTPRC, SPACA3 and TNFSF11, were associated with patient prognosis (p < 0.05). The prognostic value of stage and expression levels of 13 immune genes was analyzed and the area under the receiver operating characteristic curve (AUC) was 0.923. Based on the AUC, we divided patients into three genetic risk groups and DRFS rate was significantly different according to genetic risk groups, even in the same stage (p < 0.001).
In this study, a 13-gene expression profile in combination with stage precisely predicted distant recurrence of early TNBC. Therefore, this 13-immune-gene signature could help predict TNBC prognosis and provide guidance for treatment as well as the opportunity to develop new targets for immunotherapy in TNBC patients.
我们研究了三阴性乳腺癌(TNBC)患者免疫基因的表达谱,以确定免疫基因的预后价值及其临床意义。
在 2000 年至 2004 年期间,在三星医疗中心接受根治性手术和辅助化疗的 TNBC 患者中,使用 NanoString nCounter 分析了 770 个免疫相关基因,以测量免疫基因的表达。进行统计分析以确定基因表达与远处无复发生存(DRFS)之间的关联。
在接受根治性 BC 手术的 1189 例患者中,纳入了 200 例 TNBC 患者,而分期是唯一与 DRFS 相关的临床因素。就免疫基因而言,770 个基因中有 155 个与 DRFS 相关(p < 0.01)。进一步的多变量分析显示,13 个基因(CD1B、CD53、CT45A1、GTF3C1、IL11RA、IL1RN、LRRN3、MAPK1、NEFL、PRKCE、PTPRC、SPACA3 和 TNFSF11)与患者预后相关(p < 0.05)。分析了分期和 13 个免疫基因表达水平的预后价值,受试者工作特征曲线(ROC)下面积(AUC)为 0.923。基于 AUC,我们将患者分为三个遗传风险组,并且根据遗传风险组,即使在相同的分期,DRFS 率也有显著差异(p < 0.001)。
在这项研究中,结合分期的 13 个基因表达谱精确预测了早期 TNBC 的远处复发。因此,该 13 个免疫基因特征可帮助预测 TNBC 预后,并为治疗提供指导,并为 TNBC 患者的免疫治疗提供新的靶点机会。