Prostate cancer is one of the most common forms of cancer in men. Around 1 in 9 men will be diagnosed with the disease at some point in their lives. While the cancer is treatable if diagnosed in the early stages of the disease, in about 10% of cases, the cancer does not stay localized and metastasizes. When the cancer spreads to other organs, the disease is far more serious, treatment options are more limited, and the disease is much more likely to prove fatal.
Diagnosing patients at risk of developing metastatic prostate cancer is therefore critical, although currently there are no tissue biomarkers that can be used to predict aggressive behavior in prostate cancer and identify patients who are at risk of prostate cancer progressing to a much more serious and life-threatening form. If high-risk patients can be identified quickly, they could undergo therapies either before or after a prostatectomy to improve the prognosis.
Researchers at Yale University School of Medicine may have found a potential biomarker that could be used to identify patients at risk. The researchers discovered that the mitochondrial protein Syntaphilin (SNPH) is abundantly expressed in prostate cancer
SNPH exhibits high expression at the edge of the tumor compared to the central mass and expression increases with an increasing Gleason grade. “Prostate tumors predominantly express a novel, extraneuronal isoform of SNPH that accumulates in mitochondria and maintains oxidative metabolism and tumor cell proliferation,” wrote the researchers.
The researchers determined there was a unique, biphasic spatial distribution of SNPH in tumors from a study on 89 patients that underwent radical prostatectomy. In 96% of cases, there was elevated levels of SNPH at the tumor edge, which is associated with increased cell proliferation, and there was low central tumor expression. The low levels of SNPH in the central mass of the tumor correlated with a higher risk of metastasis.
16 patients with metastases had significantly lower levels of SNPH in the central tumor compared to patients without metastases. SNPH levels at the invasive edges of the tumors were no different between the two groups of patients.
SNPH has previously been shown to be a negative regulator of mitochondrial dynamics in neurons. The researchers suggest that in prostate tumors, SNPH is a negative regulator of mitochondrial activity and down-regulation in the central mass of the tumor is associated with an increased risk of metastatic disease.
The research backs up evidence from other studies which have suggested that SNPH plays an important role in the phenotypic switch between proliferative and metastatic tumor states and suggests that SNPH could serve as a viable biomarker for determining risk of developing metastatic disease.
The findings are encouraging, although further research is required to determine whether the findings are supported in larger studies of patients with prostate cancer.
The findings of the research are detailed in the paper – Syntaphilin Is a Novel Biphasic Biomarker of Aggressive Prostate Cancer and a Metastasis Predictor – which was recently published in The American Journal of Pathology. DOI: 10.1016/j.ajpath.2019.02.009