Abstract
Multiple copies in T‐cell lymphoma‐1 (MCTS1) plays an important role in various cancers; however, its effects on patient prognosis and immune infiltration in breast cancer remain unclear. In this study, the expression profiles and clinical information of patients with breast cancer were obtained from the Cancer Genome Atlas (TCGA) database. Using the Wilcoxon rank-sum test, the MCTS1 expression levels were compared between breast cancer and normal breast tissues. Functional enrichment analyses were performed to explore the potential signaling pathways and biological functions that are involved. Immune cell infiltration was assessed using single-sample gene set enrichment analysis. The UALCAN and MethSurv databases were used to analyze the methylation status of the MCTS1. The Kaplan-Meier method and Cox regression analysis were used to identify the prognostic value of MCTS1. A nomogram was constructed to predict the overall survival (OS) rates at one-, three-, and five-years post-cancer diagnosis. MCTS1 was overexpressed in breast cancer and significantly associated with the M pathological stage, histological type, PAM50, and increased age. MCTS1 overexpression contributes to a significant decline in OS and disease-specific survival. Multivariate Cox analysis identified MCTS1 as an independent negative prognostic marker of OS. The OS nomogram was generated with a concordance index of 0.715. Similarly, the hypomethylation status of MCTS1 is also associated with poor prognosis. Functional enrichment analysis indicated that the enriched pathways included the reactive oxygen species signaling pathway, MYC targets, interferon alpha response, immune response regulating signaling pathway, and leukocyte migration. Moreover, the overexpression of MCTS1 was negatively correlated with the levels of immune cell infiltration of natural killer cells, CD8+ T cells, effector memory T cells, and plasmacytoid dendritic cells. Therefore, MCTS1 maybe a novel prognostic biomarker.
Highlights
Breast cancer is one of the most common malignancy that threatens the health of women worldwide (Sung et al, 2021)
The pan-cancer analysis showed that the expression of Multiple copies in T-cell lymphoma-1 (MCTS1) was highly expressed in most types of cancers, such as adrenocortical carcinoma, bladder urothelial carcinoma, cervical squamous cell carcinoma, adenocarcinoma, and cholangiocarcinoma (Figure 1A)
We found that the majority of methylation sites in the DNA sequences of MCTS1 were hypomethylated in breast cancer, and the degree of methylation was correlated with patient outcomes (Figure 6B)
Summary
Breast cancer is one of the most common malignancy that threatens the health of women worldwide (Sung et al, 2021). The treatment decisions and prognosis for patients with breast cancer mainly depend on the tumor, node, and metastasis (TNM) staging system and molecular subtyping (Perou et al, 2000; Cserni et al, 2018). Clinical outcomes vary even for patients with the same tumor stage and molecular subtyping, receiving similar treatment regimens. This indicates that the current staging system is not sufficient to accurately predict prognosis, nor does it accurately represent the biological heterogeneity of breast cancer patients. Other characteristics that are intrinsic to both the tumor cells and patients may influence the clinical outcomes Studying these characteristics as prognostic markers could aid the current TNM staging system, may help predict clinical outcomes more accurately, provide better personalized treatments, and develop novel therapies for breast cancer
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