Integrated analysis of label-free quantitative proteomics and bioinformatics reveal insights into signaling pathways in male breast cancer

Abstract Male breast cancer (MBC) is a rare malignancy that accounts for about 1.8% of all breast cancer cases. In contrast to the high number of the “omics” studies in breast cancer in women, only recently molecular approaches have been performed in MBC research. High-throughput proteomics based methodologies are promisor strategies to characterize the MBC proteomic signatures and their association with clinico-pathological parameters. In this study, the label-free quantification-mass spectrometry and bioinformatics approaches were applied to analyze the proteomic profiling of a MBC case using the primary breast tumor and the corresponding axillary metastatic lymph nodes and adjacent non-tumor breast tissues. The differentially expressed proteins were identified in the signaling pathways of granzyme B, sirtuins, eIF2, actin cytoskeleton, eNOS, acute phase response and calcium and were connected to the upstream regulators MYC, PI3K SMARCA4 and cancer-related chemical drugs. An additional proteomic comparative analysis was performed with a primary breast tumor of a female patient and revealed an interesting set of proteins, which were mainly involved in cancer biology. Together, our data provide a relevant data source for the MBC research that can help the therapeutic strategies for its management.摘要 男性乳腺癌（Male breast cancer, MBC）是一种罕见的恶性肿瘤，约占所有乳腺癌病例的1.8%。相较于女性乳腺癌领域已开展大量组学（omics）研究，男性乳腺癌的分子相关研究直至近年才逐步推进。基于高通量蛋白质组学的研究方法是解析男性乳腺癌蛋白质组特征及其与临床病理参数关联的极具潜力的策略。本研究采用无标记定量质谱（label-free quantification-mass spectrometry）与生物信息学分析手段，针对一例男性乳腺癌患者的原发性乳腺肿瘤、对应腋窝转移性淋巴结及邻近非肿瘤乳腺组织开展蛋白质组谱分析。研究鉴定得到的差异表达蛋白富集于颗粒酶B、沉默信息调节因子（sirtuins）、eIF2、肌动蛋白细胞骨架、内皮型一氧化氮合酶（eNOS）、急性期反应以及钙信号通路，并与上游调控因子MYC、PI3K、SMARCA4以及癌症相关化学药物存在关联。本研究同时针对一例女性乳腺癌患者的原发性肿瘤开展了额外的蛋白质组比较分析，鉴定得到一组主要参与癌症生物学过程的特征蛋白。综上，本研究所得数据可为男性乳腺癌相关研究提供重要的数据资源，有望为该疾病的临床诊疗策略优化提供参考依据。