Sarcosine:A better marker for prostate cancer than PSA?
Recently, Liping Xie made a comment. I was also shocked by the statement that sarcosine is superior to PSA as a marker of prostate cancer.
What is sarcosine? What is it all about? It can effectively reflect the malignancy of PCa.
In fact, as I discussed earlier, there is a paradox of over-treatment and delay in the early treatment of PCa. So can this marker give us some insight? There is also a group of neuroendocrine prostate cancer in PCa. This type of tumor is very aggressive and progressive and endocrine therapy is ineffective, which is also worth thinking about and discussing.
Creatine levels reflect aggressiveness of prostate cancer
A study by Chinnaiyan et al. at the University of Michigan, Ann Arbor, in the February 12, 2009 issue of Nature (Nature 2009, 457: 910), says that a substance called sarcosine (also known as N-methylglycine, a metabolite of glycine) is a good predictor of prostate cancer aggressiveness. The study showed that a substance called sarcosine (also known as N-methylglycine, a metabolite of glycine) could effectively reflect the aggressiveness of prostate cancer and identify the growth behavior of cancer cells (slow-growing or highly aggressive).
The other two important findings of this study are that sarcosine is involved in the prostate cancer process and is one of the culprits of cellular carcinogenesis, and that the accuracy of urine sarcosine test is better than the blood prostate-specific antigen (PSA) test that is currently used in clinical practice to diagnose prostate cancer.
The sarcosine pathway:Contributing to the transformation of benign tissue to malignancy?
The researchers measured levels of 1126 metabolites in 262 histology (n=42), blood (n=110), or urine (n=110) samples from prostate cancer patients with benign prostate, limited prostate, and metastatic prostate cancers.
The researchers found that levels of at least six metabolites differed significantly between BPH and metastatic prostate tissue, with sarcosine being the most significant. Sarcosine levels were extremely low in benign prostate, substantially elevated in limited prostate cancer, and even higher in metastatic prostate cancer (Figure 1).
In addition, when sarcosine was added to the culture medium of benign prostate cells, the benign cells became invasive and showed the biological properties of cancer cells, suggesting that sarcosine may be involved in the carcinogenesis process, and thus the components involved in the sarcosine carcinogenesis pathway may become new targets for prostate cancer prevention and treatment.
Prostate cancer diagnosis: a shift from blood to urine may be possible?
In patients with elevated blood PSA (mostly >4 ng/ml) but variable prostate biopsy results (positive or negative), the investigators found that sarcosine levels in urine sediment or urine supernatant were significantly higher in patients with positive biopsies than in those with negative biopsies (Figure 2). This suggests that sarcosine is at least as good as, if not better than, PSA in detecting prostate cancer and in determining the aggressiveness of prostate cancer.
The investigators hypothesized that combining PSA testing with new biomarkers such as sarcosine, a prostate cancer-specific metabolite, could allow for more individualized diagnosis, treatment, and monitoring of prostate cancer, and most importantly, determine the severity of cancer prior to biopsy.
Methodological Implications: Can Metabolomics Research Rekindle Enthusiasm?
Another interesting aspect of this study is the methodology: it is not the genomics and proteomics studies that are so popular today, but the metabolomics studies, that is, the study of metabolites.
Metabolomics was once popular in the 1950s and 1960s, when scientists tried to understand the role of enzymes in cell biology. However, the enthusiasm for the study of genes, DNA, RNA, and proteins (especially in the search for biological markers) has since increased, leaving metabolomics in the shadows.
This new study may rekindle interest in metabolomics, as the same approach can be used to find molecular markers for other diseases. (Yan Zhang)
Industry Comments
The existing diagnosis of prostate cancer is not precise. The diagnosis is usually made by rectal examinations and blood PSA tests, and then by prostate biopsy when the diagnosis is unclear. However, even if the diagnosis of prostate cancer is made by biopsy, it is still unknown whether the biology is aggressive (prone to metastasis) or inert (less likely to metastasize). In other words, biopsy results do not help physicians determine whether a patient needs aggressive treatment. For that, we need better biomarkers. If metabolites such as sarcosine have the potential to be better markers of prostate cancer progression, then the results of this study should be validated and applied in clinical practice as soon as possible.