The Prognostic Significance of MACC1 Expression in Breast Cancer and Its Relationship to Immune Cells in the Tumor Microenvironment and Patient Survival

Abstract

Breast cancer (BC) is one of the most prevalent malignancies among females worldwide. Globally, distant metastases were reported to be responsible for a large proportion of breast cancer-related deaths. The metastasis-associated colon cancer-1 (MACC1) gene was reported as a reliable biomarker for early detection of metastasis and prediction of prognosis of breast cancer. This study investigated the prognostic significance of MACC1 in breast cancer in relation to the clinicopathologic characteristics and patients’ survival. Furthermore, the possible correlation between MACC1 expression and the different immune cells in the tumor microenvironment was explored. MACC1 mRNA was identified using quantitative reverse transcription polymerase chain reaction in 120 breast cancer specimens and adjacent non-cancerous tissues. MACC1 mRNA expression was significantly higher in the cancerous relative to the non-cancerous tissues (p < 0.001). High MACC1 expression was significantly associated with poor prognostic parameters, such as larger tumor size, grade III tumors, positive nodal metastasis, lymphovascular invasion, stage III tumors, and elevated Ki-67 expression. Higher MACC1 mRNA levels were positively correlated with CD163+ tumor-associated macrophages (r = 0.614, p < 0.001), and were negatively correlated with CD56+ natural killer cells (r = −0.398, p < 0.001) and CD8+ cytotoxic T lymphocytes (r = −0.323, p < 0.001). MACC1 expression was associated with poor patient overall survival (OS) and progression-free survival (PFS) (p < 0.001). Multivariate analysis suggested that MACC1 expression and the presence of lymphovascular invasion could be independent prognostic indicators for breast cancer (p = 0.015 and 0.042, respectively). In conclusion, MACC1 is highly expressed in cancerous tissues and is significantly related to poor prognostic factors, overall survival, and progression-free survival. MACC1 may influence infiltration of the immune cells in the tumor microenvironment, enhance immune escape of tumor cells, and may serve as a reliable independent prognostic factor for breast cancer.

Curcumin inhibits malignant behavior of colorectal cancer cells by regulating M2 polarization of tumor‐associated macrophages and metastasis associated in colon cancer 1 (MACC1) expression

“…A binding energy of −7.23 kcal/mol predicted a well binding between curcumin and MACC1. In breast cancer, a high level of MACC1 mRNA is positively correlated with CD163+ tumor associated M2 macrophages, indicating that MACC1 may enhance the immune escape of tumor cells (Ali et al, 2021). MACC1 has been highlighted in promoting tumor progression and blocking various cancer in decade‐long research (Budczies et al, 2020; Wang et al, 2021).…”

Immune Response and Metastasis—Links between the Metastasis Driver MACC1 and Cancer Immune Escape Strategies

“…A second study in breast cancer confirmed the positive effect of MACC1 on the infiltration of macrophages, in this case, specifically of anti-inflammatory, tumor-associated macrophages (TAMs). Here, however, the effect on NK cell infiltration was negatively associated with MACC1, as was the infiltration of cluster of differentiation (CD)8+ cytotoxic T lymphocytes (CTLs) [15]. Of note, one study reported that the levels of MACC1 were closely related with the expression of the immunological checkpoint programmed cell death 1 ligand 1 (PD-L1).…”

“…However, there is only limited data of MACC1 as a biomarker of immune system status and antitumor immunity. Several studies have identified correlations between MACC1 expression levels and the infiltration of immune cells into the tumor surrounding areas [14,15]. Furthermore, a bioinformatic analysis of COAD using multiple databases identified MACC1 as a potential predictor for immune responses as well as a novel target for immunotherapybased intervention strategies [74].…”

MACC1 as a Potential Target for the Treatment and Prevention of Breast Cancer

“…The potential relationship between the relative expression of MACC1 mRNA and various immune cells (CD163+ TAM, CD8+ CTL, and CD56+ NK cells) in the tumor microenvironment was investigated in order to investigate whether MACC1 can control the immunological characteristics of cancer cells while enhancing the ability of tumor cells to metastasize. MACC1mRNA expression was found in 120 BCs and paracancerous tissues using quantitative reverse transcription polymerase chain reactions, according to Ali et al [ 70 ]. MACC1mRNA levels were found to be positively correlated with CD163+ tumor-associated macrophages and negatively correlated with CD56+ natural killer cells and CD8+ cytotoxic T cells.…”