Low intratumoral genetic neutrophil-to-lymphocyte ratio (NLR) is associated with favorable tumor immune microenvironment and with survival in triple negative breast cancer (TNBC).
Low intratumoral genetic neutrophil-to-lymphocyte ratio (NLR) is associated with favorable tumor immune microenvironment and with survival in triple negative breast cancer (TNBC).
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发表时间：
2021
影响因子：
5.3
通讯作者：
Y. Tokumaru;M. Oshi;V. Murthy;W. Tian;Li Yan;F. Angarita;M. Nagahashi;N. Matsuhashi;M. Futamura;Kazuhiro Yoshida;Y. Miyoshi;K. Takabe
中科院分区：
文献类型：
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作者：
Y. Tokumaru;M. Oshi;V. Murthy;W. Tian;Li Yan;F. Angarita;M. Nagahashi;N. Matsuhashi;M. Futamura;Kazuhiro Yoshida;Y. Miyoshi;K. Takabe
三阴性乳腺癌(TNBC)患者预后不良。一种新的预后生物标志物可以通过适当地选择患者进行特定的治疗来指导治疗。外周血中性粒细胞/淋巴细胞比率(NLR)被认为与肿瘤进展有关，因此我们推测肿瘤内基因NLR将反映肿瘤免疫微环境(TIME)和乳腺癌生物学。肿瘤内遗传NLR以前定义为CD66b(CEACAM8)和CD8(CD8A)基因表达的比率，用于分析来自METABRIC、TCGA、GSE21094、GSE22358、GSE25088、GSE32646和GSE2603队列的2994名患者。在METABRIC和TCGA队列中，肿瘤内遗传NLR与肿瘤分期或肿瘤细胞增殖的临床参数(如Nottingham组织学分级或MKI67表达水平)无关。在采用不同方案的5个独立队列中，肿瘤内遗传性NLR高的乳腺癌与新辅助化疗后的病理完全缓解(PCR)无关。尽管有这些结果，肿瘤内遗传NLR高的TNBC显示出更差的无病、疾病特异性和总体存活率。肿瘤内遗传的NLR-Low TNBC富含多个免疫相关基因集，与较高的免疫相关评分和有利的时间相关，而没有基因集富含NLR-高TNBC。总之，肿瘤内遗传的NLR-Low TNBC与有利的时间和更好的生存相关。
Patients with triple negative breast cancer (TNBC) have a poor prognosis. A novel prognostic biomarker may guide management by appropriately selecting patients for particular treatments. Peripheral blood neutrophil-to-lymphocyte ratio (NLR) was reported to associate with cancer progression, thus we hypothesized that intratumor genetic NLR will reflect tumor immune microenvironment (TIME) and breast cancer biology. The intratumoral genetic NLR previously defined as the ratio of CD66b (CEACAM8) and CD8 (CD8A) gene expressions was utilized to analyze total of 2,994 patients from METABRIC, TCGA, GSE21094, GSE22358, GSE25088, GSE32646, and GSE2603 cohorts. Intratumoral genetic NLR did not correlate with cancer stage nor clinical parameters of cancer cell proliferation such as Nottingham histological grade or MKI67 expression levels in neither the METABRIC or TCGA cohorts. Intratumoral genetic NLR-high breast cancer was not associated with pathologic complete response (pCR) after neoadjuvant chemotherapy in 5 independent cohorts with different regimens. Despite these results, intratumoral genetic NLR-high TNBC demonstrated worse disease-free, disease-specific, and overall survival. Intratumoral genetic NLR-low TNBC enriched multiple immune-related gene sets, was associated with higher favorable immune-related scores and with a favorable TIME, whereas no gene sets enriched to NLR-high TNBC. In conclusion, intratumoral genetic NLR-low TNBC was associated with favorable TIME and with better survival.