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.
Highlights
Breast cancer (BC) is the most frequently occurring malignancy in women and is the second most prominent cause of cancer-associated death in women all over the world [1].Ongoing BC treatment options consistently encompass surgery if the disease is diagnosed early
Higher Metastasis-associated colon cancer gene-1 (MACC1) mRNA relative expression levels were significantly related to larger tumors >5 cm, grade III cases, positive nodal metastasis, presence of lymphovascular invasion (LVI)
This study identified a significant association between MACC1 expression and BC
Summary
Ongoing BC treatment options consistently encompass surgery if the disease is diagnosed early. Depending on the stage and the molecular subtype when diagnosed, BC treatment may involve hormonal therapy, chemotherapy, and/or radiation. Recent studies reported significant immune cell infiltration consisting of both innate and adaptive immune cells within BC tumor microenvironment [2]. Metastasis-associated colon cancer gene-1 (MACC1) was first described as a c-MET transcription regulator that mediates cancer colon progression and metastasis by its ligand hepatocyte growth factor (HGF). MACC1 was overexpressed in primary and metastatic cancer colon and was associated with poor prognosis [3]. High expression of MACC1 was proven to be related to poor clinical outcomes in a wide variety of tumors, such as gastric, endometrial, and ovarian carcinomas [4,5,6]
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