Prognostic genes in pancreatic cancer


MUC1.jpg
Figure 1. Immunohistochemical staining of MUC1 shows differential expression pattern, high (left panel) and low (right panel) in
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Figure 2. Immunohistochemical staining of PELP1 shows differential expression, high (left panel) and low (right panel), in samples from pancreatic cancer patients.

1527 genes are found to be associated with prognosis in pancreatic cancers and 670 of them correlate with unfavourable prognosis. As part of the Pathology Atlas, release, we present brief and informative summaries of all cancers, and highlight genes with prognostic association in the different cancer forms.

Next in our series of articles on cancer is Pancreatic cancer, a relatively rare cancer associated with very poor prognosis. The vast majority of tumors originate from ductal cells and a small fraction are endocrine tumors. Over 80% of pancreatic cancers develop at ages above 60 years and most tumors are detected at late stages of the disease when the cancer has spread beyond the pancreas.

There is a great need for biomarkers to facilitate early detection and help establishment of diagnosis. Smoking, obesity, physical inactivity and long-lasting inflammation in the pancreas are some of the factors that lead to an increased risk of pancreatic cancer. Studies have found an association between lifestyle changes and pancreatic cancer diagnosis.

The analysis of prognostic genes in pancreatic cancer was based on publically available gene expression data and clinical metadata from The Cancer Genome Atlas, consisting of 176 patients with different stages of pancreatic cancer. According to the analysis, 1527 genes were associated with prognostic outcome, out of which 670 genes were associated with unfavourable prognosis and 857 genes with favourable prognosis.

The cell surface associated protein Mucin 1 is encoded by the MUC1 gene. It creates a barrier on the surface of epithelial cells to serve as protection against pathogens and harmful molecules. A tumor-associated form is overexpressed in epithelial cancers and plays an important role in tumor progression. Unlike normal cells, cancer cells lack cell-polarity and therefore this protein is distributed in the cytoplasm of cancer cells. In our analysis, higher mRNA expression of MUC1 was shown to be associated with unfavourable prognosis in pancreatic cancer patients. Immunohistochemical staining of MUC1 shows a differential cytoplasmic expression pattern in pancreatic cancer samples (Figure 1).

Proline, glutamic acid- and leucine-rich protein 1 is encoded by the PELP1 gene. It is involved in transcription regulation by interacting with nuclear hormone receptors and transcription factors. These genes include estrogen alpha and also genes implicated in tumor development, invasiveness and metastasis. In our analysis, higher mRNA expression of PELP1 was shown to be associated with favourable prognosis in pancreatic cancer patients. Immunohistochemical staining of PELP1 shows a differential nuclear expression pattern in pancreatic cancer samples (Figure 2). To explore the Pancreatic cancer proteome and specific genes expressed in pancreatic cancer visit the new Pathology Atlas.

If you missed the launch summary of the Pathology Atlas, you can access it here, as well as the related research article, published in Science in August (Uhlen et al. 2017).

References


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

Links


Pancreatic Cancer Dictionary