Highlighting the prognostic genes in colon cancer

Figure 1. Immunohistochemical staining of JDP2 protein using HPA059511 antibody shows a differential expression in samples from colorectal cancer patients.
Figure 2. Immunohistochemical staining of ABCD3 protein using HPA032026 antibody shows differential expression in samples from colorectal cancer patients.

Last week the Human Protein Atlas portal was updated with a new Pathology Atlas - an interactive atlas where the expression of specific genes and their influence on patient survival in the 17 major cancer types can be explored. The Pathology Atlas includes quantitative genome-wide transcriptomics data (RNA-seq) of the 17 cancers coupled with clinical outcome and spatial proteomics data (immunohistochemistry) of more than 15,000 proteins.

During the next weeks, we will highlight different cancer types included in the analysis and also show examples of genes with unfavourable and favourable prognostic significance. This week's news article features colorectal cancer.

Colorectal Cancer is the third most common cancer in the world and the cancer originates from normal colon epithelium that develops into polyps and precursor lesions termed adenomas. Subsequently, the lesions transform and progress to invasive colorectal adenocarcinomas with metastatic potential.

Despite being the fifth leading cause of cancer-related mortality, the 5-year survival of early stage patients is more than 90%. However, for advanced stage cancer, the chance of survival drops significantly and unfortunately, most colorectal cancer cases are detected at advanced stage.

In our analysis, we used publicly available gene expression data from the Cancer Genome Atlas, or TCGA, based on transcriptomics data and clinical metadata from 597 patients with different stages of colorectal cancer. The analysis shows that 595 genes are associated with either unfavourable or favourable prognosis. In total, 243 genes were associated with unfavourable prognosis whereas 352 genes were associated with favorable prognosis.

The Jun dimerization protein 2, encoded by the JDP2 gene, is a transcription factor involved in a variety of responses linked to UV-induced apoptosis, cell differentiation and anti-tumorigenesis. The JDP2 gene is shown to be associated with unfavourable prognosis in colon adenocarcinoma. Immunohistochemical staining of JDP2 shows a nuclear expression pattern in colorectal cancer samples (Figure 1).

The ABCD3 gene encodes a member of the ATP-binding cassette superfamily. The ABCD3 protein is involved in the transport of branched fatty acids and bile acid via the peroxisome machinery. The ABCD3 gene has previously not been linked to any cancer form. However, we show that higher expression the ABCD3 gene is associated with favourable prognosis in colon adenocarcinomas. Immunohistochemical staining of ABCD3 shows a granular cytoplasmic staining pattern in several samples of colorectal cancer tissue (Figure 2). The Colorectal cancer proteome can be explored in detail in the new Pathology Atlas!

The launch of the Pathology Atlas has been described previously on our portal in a news article, and the related scientific publication, in the latest issue of Science.

References and links

Uhlén M et al, 2017. A Pathology Atlas of the Human Cancer Transcriptome. Science DOI: 10.1126/science.aan2507

Feria Hikmet Noraddin