High expression of LC3B is associated with progression and poor outcome in triple-negative breast cancer

Abstract

Microtubule-associated protein 1 light chain 3B (LC3B) was involved in autophagosome formation and had been as a marker of autophagy which played an important role in the development of breast cancer. The purpose of this study was to explore the level of LC3B expression in four stages of triple-negative breast cancer (TNBC) and to evaluate the prognostic significance of LC3B expression in TNBC. The ultimate aim was to identify the new factor that could be useful in predicting clinical behavior of TNBC. We evaluated the expression level of LC3B protein in four kinds of TNBC tissue samples, including intraductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) without metastases, IDC with lymph node metastases (LNM), and IDC with distant metastases (DM). Hundred and four primary TNBC patients were involved in present study, and the expression level of LC3B protein was assessed by immunohistochemistry. Medical records of these patients were reviewed, and the clinicopathological analysis was performed. High expression of LC3B was observed in 7.7 % of DCIS (1 of 13 cases), 16.2 % of IDC (6 of 37 cases), 35.7 % of LNM (15 of 42 cases), and 58.3 % of DM (7 of 12 cases). LC3B high expression was significantly associated with tumor size (P = 0.028), lymph node metastasis (P = 0.002), and Ki-67 expression (P = 0.047). LC3B high expression patients showed poorer DFS and OS rates compared with LC3B low expression patients (P = 0.024, and P = 0.047, respectively). Multivariate analyses confirmed that high LC3B expression was an independent and significant factor for predicting the poor outcome of TNBC patients. These preliminary results demonstrated that high LC3B expression was associated with lymph node and distant metastasis. Furthermore, high LC3B protein expression was correlated with shorter survival in patients with triple-negative breast carcinoma. These findings provided preliminary evidence for the function of LC3B on the progression of TNBC and suggested LC3B was a useful marker in prognostic evaluation for patients with TNBC.

Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer

“…27,30 In a cohort of patients with locally advanced BC that received neoadjuvant chemotherapy, a high intensity of LC3B staining was described as a (negative) independent prognostic factor for relapse-free and overall survival, 27 in particular in triple-negative cancers. 31 A recent meta-analysis confirmed that high expression of LC3B predicts adverse OS in BC. 32 However, none of the aforementioned studies was based on the quantification of LC3B C puncta, and rather scored the overall expression level of LC3B, meaning that the evaluation criteria was rather different from those reported here.…”

Autophagy Inhibition Augments the Anticancer Effects of Epirubicin Treatment in Anthracycline-Sensitive and -Resistant Triple-Negative Breast Cancer

“…6C) showed elevated levels of LC3B protein in R8 tumors compared with the MDA-MB-231 parental tumors, suggesting that resistant tumors also maintain higher levels of autophagy in vivo even when the selective pressure (epirubicin) is not present. Recent IHC studies have described an association between elevated expression of autophagy proteins LC3A, LC3B, and Beclin 1 in TNBC tumors compared with other molecular subtypes of breast cancer (36) and high LC3B was associated with progression and poor outcome in TNBC (37). Understanding the functional significance of elevated autophagy in different breast cancer cell types, along with the potential role and molecular mechanisms of autophagy in drug resistance, will be important areas for future study.…”

Upregulation of ATG3 contributes to autophagy induced by the detachment of intestinal epithelial cells from the extracellular matrix, but promotes autophagy-independent apoptosis of the attached cells

“…32,34,35,42,43 Furthermore, levels of some of these mediators are altered in diverse types of human tumors. 44,45 Based on the changes in these levels, conclusions regarding the role of autophagy in the progression of respective cancers were made. 44,45 However, some critical mediators of autophagy seem to be able to play autophagy-unrelated roles in cells.…”

“…44,45 Based on the changes in these levels, conclusions regarding the role of autophagy in the progression of respective cancers were made. 44,45 However, some critical mediators of autophagy seem to be able to play autophagy-unrelated roles in cells. For example, ATG12, one of the important stimulators of autophagosome formation, was found to cause apoptosis via physical interactions with components of the cellular apoptotic machinery (such as the BCL2 family members) in a manner independent of its ability to trigger autophagy.…”

“…37,44,45 To our knowledge, whether or not ATG3 levels change in the course of progression of any cancers has not yet been explored. Our data indicate that if changes in ATG3 expression are found in the future in human cancers, these changes could reflect the contribution of not only autophagy but also that of ATG3-dependent apoptosis in the course of the respective diseases.…”