Division of Breast Surgery, Department of Surgery, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Republic of Korea.
Department of Surgery, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Republic of Korea.
PLoS One. 2021 May 26;16(5):e0252052. doi: 10.1371/journal.pone.0252052. eCollection 2021.
Matrix metalloproteinase-11 (MMP-11) promote cancer invasion and metastasis through degrading the extracellular matrix. Protein degradation by MMP-11 in tumor cells may progressively suppress cancer surveillance activities with blocking immune response in breast cancer. The aim of study is to analyze clinicopathological parameters, molecular interactions and anticancer immune response in patients with MMP-11 expression and to provide candidate target drugs. We investigated the clinicopathologic parameters, specific gene sets, tumor antigenicity, and immunologic relevance according to MMP-11 expression in 226 and 776 breast cancer patients from the Hanyang University Guri Hospital (HUGH) cohort and The Cancer Genome Atlas (TCGA) data, respectively. We analyzed pathway networks and in vitro drug response. High MMP-11 expression was associated with worse survival rate in breast cancer from HUGH cohort and TCGA data (all p < 0.05). In analysis of immunologic gene sets, high MMP-11 expression was related to low immune response such as CD8+T cell, CD4+T cell and B cell. In silico cytometry, there was a decrease of cancer testis antigen and low tumor infiltrating lymphocyte in patient with high MMP-11 expression: activated dendritic cell, CD8+T cell, CD4+ memory T cell, and memory B cell. In pathway networks, MMP-11 was linked to the pathways including low immune response, response to growth hormone and catabolic process. We found that pictilisib and AZ960 effectively inhibited the breast cancer cell lines with high MMP-11 expression. Strategies making use of MMP-11-related hub genes could contribute to better clinical management/research for patients with breast cancer.
基质金属蛋白酶-11（MMP-11）通过降解细胞外基质促进癌症侵袭和转移。肿瘤细胞中 MMP-11 的蛋白降解可能会逐渐抑制乳腺癌中的癌症监测活动并阻断免疫反应。本研究旨在分析 MMP-11 表达患者的临床病理参数、分子相互作用和抗癌免疫反应，并提供候选靶向药物。我们根据 226 名和 776 名来自韩阳大学古里医院（HUGH）队列和癌症基因组图谱（TCGA）数据的乳腺癌患者的 MMP-11 表达，分别研究了临床病理参数、特定基因集、肿瘤抗原性和免疫相关性。我们分析了通路网络和体外药物反应。HUGH 队列和 TCGA 数据均显示 MMP-11 高表达与乳腺癌患者生存率较差相关（均 P<0.05）。在免疫基因集分析中，MMP-11 高表达与低免疫反应相关，如 CD8+T 细胞、CD4+T 细胞和 B 细胞。在计算机细胞术分析中，高 MMP-11 表达患者的癌症睾丸抗原减少，肿瘤浸润淋巴细胞减少：活化的树突状细胞、CD8+T 细胞、CD4+记忆 T 细胞和记忆 B 细胞。在通路网络中，MMP-11 与包括低免疫反应、对生长激素的反应和分解代谢过程在内的通路相关。我们发现 pictilisib 和 AZ960 可有效抑制 MMP-11 高表达的乳腺癌细胞系。利用 MMP-11 相关枢纽基因的策略可能有助于改善乳腺癌患者的临床管理/研究。
