Jeong Young Ju, Park Sung Hwan, Mun Sung Hee, Kwak Sang Gyu, Lee Sun-Jae, Oh Hoon Kyu
Department of Surgery, College of Medicine, Catholic University of Daegu, Daegu 705-718, Repulic of South Korea.
Department of Radiology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Repulic of South Korea.
Oncol Lett. 2018 Feb;15(2):2431-2440. doi: 10.3892/ol.2017.7617. Epub 2017 Dec 14.
We hypothesized that lysyl oxidase (LOX) contributes to the formation of fibrotic focus (FF) in association with inflammation and serves a significant role in breast carcinogenesis. In the present study, the association between the expression of LOX family members and FF with regards to with inflammation was analyzed, and the prognostic significance of LOX and FF in breast cancer was investigated. Immunohistochemical staining for LOX, LOX-like protein (LOXL) 1, LOXL2 and LOXL3 was performed in primary breast cancer tissues. The status of FF within the tumor was assessed, including size and grade. Levels of inflammatory markers, intratumoral and peritumoral lymphocyte infiltration were also evaluated. The clinicopathological characteristics were evaluated from the medical records of patients. In the present study, the expression of LOX family members was not associated with the presence of FF. FF was identified to be associated with intratumoral and peritumoral inflammation, tumor stage, larger tumor size, lymph node metastasis, high histologic grade, and p53 expression. LOX and LOXL3 were associated with intratumoral, and peritumoral inflammation. Furthermore, LOXL1 was associated with intratumoral inflammation and interleukin-4. In addition, LOX was associated with cluster of differentiation 8 T cells. LOXL3 was associated with expression of ER and PR, and molecular subtype. In the survival analysis, overall survival time was statistically significantly longer in the FF-negative compared with that in the FF-positive group. In conclusion, it was demonstrated that FF and the expression of LOX family members were associated with inflammation in breast cancer. FF was associated with poor prognostic markers of breast cancer. Further studies are required to clarify the mechanisms underlying the association between the LOX family, FF and inflammation in breast cancer.
我们推测赖氨酰氧化酶（LOX）与炎症相关，有助于纤维化病灶（FF）的形成，并在乳腺癌发生过程中发挥重要作用。在本研究中，分析了LOX家族成员的表达与FF在炎症方面的关联，并研究了LOX和FF在乳腺癌中的预后意义。对原发性乳腺癌组织进行了LOX、类赖氨酰氧化酶蛋白（LOXL）1、LOXL2和LOXL3的免疫组织化学染色。评估了肿瘤内FF的状态，包括大小和分级。还评估了炎症标志物水平、肿瘤内和肿瘤周围淋巴细胞浸润情况。从患者的病历中评估临床病理特征。在本研究中，LOX家族成员的表达与FF的存在无关。FF被确定与肿瘤内和肿瘤周围炎症、肿瘤分期、较大的肿瘤大小、淋巴结转移、高组织学分级和p53表达相关。LOX和LOXL3与肿瘤内和肿瘤周围炎症相关。此外，LOXL1与肿瘤内炎症和白细胞介素-4相关。另外，LOX与分化簇8 T细胞相关。LOXL3与雌激素受体（ER）和孕激素受体（PR）的表达以及分子亚型相关。在生存分析中，FF阴性组的总生存时间在统计学上显著长于FF阳性组。总之，结果表明FF和LOX家族成员的表达与乳腺癌中的炎症相关。FF与乳腺癌的不良预后标志物相关。需要进一步研究以阐明LOX家族、FF与乳腺癌炎症之间关联的潜在机制。
