Zhong Jing-Min, Li Jing, Kang An-Ding, Huang San-Qian, Liu Wen-Bin, Zhang Yun, Liu Zhi-Hong, Zeng Liang
Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Department of Pathology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
Oncol Lett. 2018 Apr;15(4):5285-5293. doi: 10.3892/ol.2018.7958. Epub 2018 Feb 6.
Breast cancer is the most common malignancy in females, with metastasis of this type of cancer frequently proving lethal. However, there are still no effective biomarkers to predict breast cancer metastasis. The aim of the present study was, therefore, to analyze breast cancer metastasis-associated proteins and evaluate the association between protein S100-A8 and the prognosis of breast cancer. The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic technique was used to analyze the differential expression of proteins between fresh primary breast tumor (PBT) tissue and fresh paired metastatic lymph nodes (PMLN) tissue. Subsequently, immunohistochemical staining was used to locate and assess the expression of protein S100-A8 in benign breast disease (n=15), primary breast cancer with (n=109) or without (n=83) metastasis, and in paired metastatic lymph nodes (n=109) formalin fixed paraffin embedded (FFPE) tissue. Staining scores were evaluated and the association between protein S100-A8 expression levels and the clinicopathological characteristics of 192 patients with breast cancer were evaluated using the χ test. Kaplan-Meier and Cox hazards regression analyses were utilized to investigate the association between the expression of protein S100-A8 and the prognosis of patients with breast cancer. A total of 4,837 proteins were identified using the iTRAQ proteomic technique. Among these proteins, 643 differentially expressed proteins were revealed. Protein S100-A8 expression levels were identified to differ between PBT and PMLN tissues. Immunohistochemical staining suggested a significant difference between NMBT and PMLN (P=0.002), and also between PBT and PMLN (P<0.001). Cox hazards regression model analyses suggested that histological grade (P=0.031) and nodal status (P=0.001) were risk factors for lymph nodes metastasis of breast cancer. Kaplan-Meier analyses revealed no significant relationship between protein S100-A8 expression level and overall survival rate of patients with breast cancer. In conclusion, by using the iTRAQ proteomic technique and immunohistochemistry staining, it was identified that protein S100-A8 may be associated with lymph nodes metastasis of breast cancer and be a marker for progression of breast cancer.
乳腺癌是女性最常见的恶性肿瘤，这种癌症的转移常常是致命的。然而，目前仍没有有效的生物标志物来预测乳腺癌转移。因此，本研究的目的是分析与乳腺癌转移相关的蛋白质，并评估蛋白质S100 - A8与乳腺癌预后之间的关联。采用相对和绝对定量同位素标记（iTRAQ）蛋白质组学技术分析新鲜原发性乳腺肿瘤（PBT）组织与新鲜配对转移淋巴结（PMLN）组织之间蛋白质的差异表达。随后，采用免疫组织化学染色法对15例良性乳腺疾病、109例有转移或83例无转移的原发性乳腺癌以及109例配对转移淋巴结的福尔马林固定石蜡包埋（FFPE）组织中蛋白质S100 - A8的表达进行定位和评估。评估染色评分，并采用χ检验评估192例乳腺癌患者蛋白质S100 - A8表达水平与临床病理特征之间有关联。采用Kaplan - Meier法和Cox风险回归分析来研究蛋白质S100 - A8的表达与乳腺癌患者预后之间的关联。使用iTRAQ蛋白质组学技术共鉴定出4837种蛋白质。在这些蛋白质中，发现了643种差异表达蛋白质。已确定蛋白质S100 - A8在PBT和PMLN组织中的表达水平存在差异。免疫组织化学染色显示非转移性乳腺癌（NMBT）与PMLN之间存在显著差异（P = 0.002），PBT与PMLN之间也存在显著差异（P < 0.001）。Cox风险回归模型分析表明，组织学分级（P = 0.031）和淋巴结状态（P = 0.001）是乳腺癌淋巴结转移的危险因素。Kaplan - Meier分析显示，蛋白质S’100 - A8表达水平与乳腺癌患者的总生存率之间无显著关系。总之，通过使用iTRAQ蛋白质组学技术和免疫组织化学染色，已确定蛋白质S100 - A8可能与乳腺癌的淋巴结转移有关，并且是乳腺癌进展的一个标志物。
