Abstract
MYC is one of the most studied oncogenes that is known to promote cell proliferation. We utilized MYC targets v1 and MYC targets v2 scores of gene set variation analysis and hypothesized that these scores correlate with tumor aggressiveness and survival outcomes. We examined a total of 3109 breast cancer patients from TCGA, METABRIC, and GSE124647 cohorts. In each cohort, the patients were divided into high- and low-score groups using the upper third value as the cut off. As expected, higher scores were related to increased cell proliferation and worse clinical and pathologic features. High MYC targets scores were associated with worse survival, specifically in primary ER-positive breast cancer, consistently in both TCGA and METABRIC cohorts. In ER-positive breast cancer, high MYC targets v1, but not v2 score, was associated with high mutation load, and high MYC targets v1 and v2 scores were both associated with increased infiltration of pro- and anti-cancerous immune cells. We found that high MYC scores were associated with worse survival in metastatic breast cancer. Our findings show that the MYC targets v1 and v2 scores are associated with tumor aggressiveness and poor prognosis in ER-positive primary tumors, as well as in metastatic breast cancer.
Highlights
Breast cancer is currently the most prevalent cancer among women in the United States and it is estimated that 40,000 women in the US will die from the disease in 2020 [1]
Given that MYC is one of the most studied oncogenes, we expected that both MYC scores would correlate with cell proliferation, which was assessed by the proliferation score, precalculated in the The Cancer Genome Atlas (TCGA) cohort by Thorsson et al [21], and expression of MKI67 that encodes KI67, the most commonly used marker for cell proliferation in the clinic [22]
These findings suggest that breast cancer with high MYC targets v1 or MYC targets v2 scores are associated with higher proliferation compared to low scores
Summary
Breast cancer is currently the most prevalent cancer among women in the United States and it is estimated that 40,000 women in the US will die from the disease in 2020 [1]. It has been shown that even with breast cancers of similar stage and subtype, there is variability in clinical response to treatment, opening the possibility of personalized treatment of a patient’s specific breast cancer [3]. There are currently two multigene risk scores that are routinely used in patient care, Oncotype and MammaPrint. Both have been shown to have prognostic use in the clinical setting, there remain limitations. The technological advances in recent years for genetic analyses of tumors, as well as the subsequent cost reduction, creates the opportunity for use of a prognostic score that is both more expansive in the number of genes evaluated and more specific to one of the cancer hallmarks
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