Association between lysyl oxidase and fibrotic focus in relation with inflammation in breast cancer

Abstract

Abstract. 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.

Peer Review #1 of "Association between the degree of fibrosis in fibrotic focus and the unfavorable clinicopathological prognostic features of breast cancer (v0.1)"

“…Mujtab et al (Mujtaba et al 2013) demonstrated that the FF was more common in Luminal A subtype than in non-Luminal A subtype (n = 450, P < 0.001). But another study (Jeong et al 2018) did not find the association between FF and molecular subtypes (n = 291, P = 0.830). The different conclusions might be due to the inconsistencies of baseline PeerJ reviewing PDF | (2019:08:39938:1:1:NEW 11 Oct 2019)…”

“…Mujtaba et al (Mujtaba et al 2013) revealed that FF was negatively associated with HER-2 expression (P = 0.021) and Ki-67 index (P = 0.001) and positively associated with HR expression (P = 0.007). However, Jeong et al (Jeong et al 2018) did not find that FF was related to the expression of HR, HER-2, and Ki-67. The results of the studies above were controversial, which may be caused by the followings.…”

“…Hasebe et al (Hasebe et al 1996) demonstrated that the histological grade and lymph node metastasis rate were higher in breast cancer with FF, especially in that with tumor size< 5cm. Jeong et al (Jeong et al 2018) revealed that the FF was significantly associated with tumor size > 2cm, lymph node metastasis, poor differentiation, and vascular invasion in breast cancer. The studies mentioned above had indicated that FF was closely related with the adverse pathological characteristics of breast cancer.…”

Analysis of Genetically Determined Gene Expression Suggests Role of Inflammatory Processes in Etiology of Exfoliation Syndrome

“…ARID3B, CD276, LOXL1 and NEO1 are immunoregulatory molecules involved in the interaction between different tumors and the immune system. [43][44][45][46] SCAMP2 is important in granule exocytosis, a process crucial in membrane fusion in normal cellular functions in diverse systems including the immune system's inflammatory response. [47][48][49] CD276 is involved in regulation of Ag-specific T cell-mediated immune responses and participates in the innate immunity-associated inflammatory response.…”

“…[47][48][49] CD276 is involved in regulation of Ag-specific T cell-mediated immune responses and participates in the innate immunity-associated inflammatory response. 50,51 LOXL1 has also been implicated in fibrosis in response to inflammation in human breast cancer, 52 in liver and lungs in model animals. [53][54][55] UBL7 encodes a member of the ubiquitin protein family, that is crucial in immune response and regulation of inflammatory response.…”