PTEN, MAN2C1, and the identification of potentially aggressive forms of prostate cancer

A new article in Nature Communications has suggested that we may be able to specifically identify some aggressive forms of prostate cancer cells that come with high risk for metastatic prostate cancer even at low PSA levels and other less aggressive forms of prostate cancer cell.

The original article by He et al. may be a little hard for the average reader to “digest,” so it may be worth having a look at the commentary on the Science Daily web site.

The bottom line to the research is that patients with elevated levels of a protein known as MAN2C1 or α-mannosidase 2C1 appear to be at greater risk for aggressive disease. Why? Because high levels of MAN2C1 seems to be associated with lowered levels of another protein known as PTEN (phosphatase and tensin homolog), and we know that men with low levels of PTEN are at greater risk for aggressive forms of prostate cancer.

He and her colleagues used mouse model studies to demonstrate that MAN2C1 does actually work as “a PTEN-negative regulator” in prostate cancer cells in the laboratory. However, they also looked at data from 659 men with prostate cancer, and found that:

  • About 60 per cent of the prostate tumors in these men had normal PTEN levels.
  • Of the men with normal PTEN levels, 80 per cent had increased levels of MAN2C1.

The researchers believe that heightened levels of MAN2C1 in patients with PTEN-positive prostate cancers are associated with an increased risk for prostate cancer recurrence, which clearly raises risk for metastatic disease and potentially prostate cancer-specific mortality. It is therefore possible that (a) simple diagnostic tests could be developed to assess levels of PTEN and MAN2C1 in blood or biopsy samples at the time of diagnosis and (b) that new types of drug could be developed to block or down-regulate levels of MAN2C1.

One Response

  1. This information may already be incorporated into the prostate cancer tests developed by Myriad Genetics and in development at Genomic Health. Both tests work by measuring the expression (in cancer cells of a particular tumor) of most of the genes that have been implicated in prostate cancer pathways. An algorithim looks at the expression level of each gene and derives a score indicating the likely aggressiveness of the cancer. Genomic Health has had a test on the market for several years that predicts the likelihood of recurrence of a certain type of breast cancer after surgery. For years, even though doctors knew that only about 10% of women would benefit from follow-up treatment with chemotherapy, they would recommend such treatment for all women (just in case). This test has spared tens of thousands of women an unnecessary encounter with chemotherapy.

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