Oshi Masanori, Angarita Fernando A, Tokumaru Yoshihisa, Yan Li, Matsuyama Ryusei, Endo Itaru, Takabe Kazuaki
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Cancers (Basel). 2020 Dec 21;12(12):3856. doi: 10.3390/cancers12123856.
Nuclear factor erythroid 2-related factor 2 () is a key modifier in breast cancer. It is unclear whether NRF2 suppresses or promotes breast cancer progression. We studied the clinical relevance of expression by conducting in silico analyses in 5443 breast cancer patients from several large patient cohorts (METABRIC, GSE96058, GSE25066, GSE20194, and GSE75688). expression was significantly associated with better survival, low Nottingham pathological grade, and ER-positive/HER2-negative and triple negative breast cancer (TNBC). High ER-positive/HER2-negative breast cancer enriched inflammation- and immune-related gene sets by GSEA. expression was elevated in immune, stromal, and cancer cells. High tumors were associated with high infiltration of immune cells (CD8, CD4, and dendritic cells (DC)) and stromal cells (adipocyte, fibroblasts, and keratinocytes), and with low fraction of Th1 cells. expression significantly correlated with area under the curve (AUC) of several drug response in multiple ER-positive breast cancer cell lines, however, there was no significant association between and pathologic complete response (pCR) rate after neoadjuvant chemotherapy in human samples. Finally, high breast cancer was associated with high expression of immune checkpoint molecules. In conclusion, expression was associated with enhanced tumor-infiltrating lymphocytes in ER-positive/HER2-negative breast cancer.
核因子红细胞2相关因子2（NRF2）是乳腺癌中的关键调节因子。目前尚不清楚NRF2是抑制还是促进乳腺癌进展。我们通过对来自几个大型患者队列（METABRIC、GSE96058、GSE25066、GSE20194和GSE75688）的5443例乳腺癌患者进行计算机分析，研究了NRF2表达的临床相关性。NRF2表达与更好的生存率、低诺丁汉病理分级以及雌激素受体阳性/人表皮生长因子受体2阴性和三阴性乳腺癌（TNBC）显著相关。通过基因集富集分析（GSEA），雌激素受体阳性/人表皮生长因子受体2阴性乳腺癌中高NRF2表达富集了炎症和免疫相关基因集。NRF2在免疫细胞、基质细胞和癌细胞中表达升高。高NRF2肿瘤与免疫细胞（CD8、CD4和树突状细胞（DC））和基质细胞（脂肪细胞、成纤维细胞和角质形成细胞）高浸润以及Th1细胞低比例相关。NRF2表达与多种雌激素受体阳性乳腺癌细胞系中几种药物反应的曲线下面积（AUC）显著相关，然而，在人类样本中，NRF2与新辅助化疗后的病理完全缓解（pCR）率之间没有显著关联。最后，高NRF2乳腺癌与免疫检查点分子的高表达相关。总之，NRF2表达与雌激素受体阳性/人表皮生长因子受体2阴性乳腺癌中肿瘤浸润淋巴细胞的增加有关。
