Oshi Masanori, Gandhi Shipra, Huyser Michelle R, Tokumaru Yoshihisa, Yan Li, Yamada Akimitsu, Matsuyama Ryusei, Endo Itaru, Takabe Kazuaki
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center Buffalo, New York 14263, USA.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine Yokohama 236-0004, Japan.
Am J Cancer Res. 2021 Sep 15;11(9):4421-4437. eCollection 2021.
In experimental settings, maternal embryonic leucine zipper kinase (), an apical member of the snf1/AMPK serine-threonine kinases family, plays a role in tumor growth. We investigated the clinical relevance of expression by performing silico analyses of 7,135 breast cancer patients using multiple independent large cohorts. In triple negative breast cancer (TNBC) found that elevated expression significantly correlates with Nottingham histologic grade and tumor growth according to American Joint Committee Cancer (AJCC) stage. High tumor enriched cell proliferation-related gene sets as well as DNA repair, unfolded protein response, and MTORC signaling gene sets. In two independent cohorts a high mutation rate and worse survival was significantly associated with high tumor. In immune-related gene sets including, allograft rejection, interferon (IFN)-α response, and IFN-γ response, high tumor significantly enriched. Pro-cancer regulatory T cells, T helper type 2 cells and anti-cancer immune cells including CD4 memory T cells, T helper type1 cells, CD8 T cells, M1 macrophages, gamma-delta T cells, and dendritic cells with high levels of cytolytic activity (CYT) were highly infiltrated. expression did not correlate with the responses to any of the drugs tested in cell lines. However, pathologic complete response was significantly associated with high following NAC in both TNBC and ER-positive plus HER2-negative breast cancer. In conclusion, cell proliferation, immune response, and NAC breast cancer response was associated with expression.
在实验环境中，母体胚胎亮氨酸拉链激酶（）是snf1/AMPK丝氨酸 - 苏氨酸激酶家族的顶端成员，在肿瘤生长中发挥作用。我们通过使用多个独立的大型队列对7135例乳腺癌患者进行计算机分析，研究了 表达的临床相关性。在三阴性乳腺癌（TNBC）中发现，根据美国癌症联合委员会（AJCC）分期， 表达升高与诺丁汉组织学分级和肿瘤生长显著相关。高 肿瘤富含细胞增殖相关基因集以及DNA修复、未折叠蛋白反应和MTORC信号基因集。在两个独立队列中，高 肿瘤与高突变率和较差的生存率显著相关。在包括同种异体移植排斥、干扰素（IFN）-α反应和IFN-γ反应的免疫相关基因集中，高 肿瘤显著富集。具有高细胞溶解活性（CYT）的促癌调节性T细胞、2型辅助性T细胞和抗癌免疫细胞，包括CD4记忆T细胞、1型辅助性T细胞、CD8 T细胞、M1巨噬细胞、γδ T细胞和树突状细胞高度浸润。 表达与细胞系中测试的任何药物的反应均无相关性。然而，在TNBC和雌激素受体阳性加人表皮生长因子受体2阴性乳腺癌中，病理完全缓解与新辅助化疗后高 显著相关。总之，细胞增殖、免疫反应和新辅助化疗乳腺癌反应与 表达相关。
