Focusing on prognostic genes in breast cancer

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Figure 1. Immunohistochemical staining of CBX3 using antibody HPA004902 shows a differential nuclear expression in samples from breast cancer patients.
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Figure 2. Immunohistochemical staining of MVP using antibody HPA064740 shows differential cytoplasmic expression in samples from breast cancer patients

The Pathology Atlas, recently published in Science presents key proteins associated with different cancer types. This week's news article will focus on breast cancer and proteins related to cancer prognosis.

Breast cancer is the most common invasive cancer form in women worldwide. The cancer can roughly be classified as ductal or lobular breast cancer depending on the origin. The majority of breast cancers develop sporadically, but for 5-10% of patients there is an inherited factor associated with increased breast cancer risk, namely the BRCA1 and BRCA2 genes. Women with abnormal BRCA1 or BRCA2 have higher risk of developing breast cancer. Other risk factors include early menarche and late menopause. The rate of breast cancer diagnosis increased during the 1990's, but has decreased since year 2000 and the overall breast cancer death rate has dropped steadily in the western countries.

The analysis of prognostic genes in breast cancer was based on publicly available gene expression data and clinical metadata from the Cancer Genome Atlas (TCGA) consisting of 1075 patients with different stages of breast cancer. According to the analysis 575 genes were associated with prognostic outcome, out of which 209 genes were associated with unfavorable prognosis and 366 genes with favorable prognosis.

The DNA-binding Chromobox protein homolog 3 is encoded by the CBX3 gene and component of the heterochromatin, thus important in transcriptional silencing. In our analysis, higher mRNA expression of CBX3 was shown to be associated with unfavorable prognosis in breast cancer patients. CBX3 showed a differential nuclear expression pattern in breast cancer samples (Figure 1).

The Major Vault Protein, or MVP is an important component of large ribonucleoprotein particles found in eukaryotic cells. The MVP protein may play a role in several cellular functions such as signaling pathway regulation of the JAK/STAT, PI3K/AKT and MAP kinase pathways. MVP also seems to be implicated in multi-drug resistance and previous reports link the expression of MVP to prognosis in several cancer types. In our analysis, higher mRNA expression of MVP was shown to be associated with favorable prognosis in breast cancer patients. Immunohistochemical staining of MVP showed a differential cytoplasmic expression pattern in breast cancer samples (Figure 2).

To explore in detail the Breast cancer proteome and search for interesting genes visit our new Pathology Atlas.

As part of the release of the Pathology Atlas, the Human Protein Atlas will each week present a brief and informative summary where we highlight genes with prognostic association in different cancer forms. Click here if you missed last week's news about prognostic genes in colon cancer.

Feria Hikmet Noraddin