Prostate Cancer Severity Indicated by Location and Concentration of Syntaphilin

A biomarker has been identified that may enable doctors to predict which patients with early indications of prostate cancer will be likely to develop the much more serious invasive and metastatic form of the disease.

About 10% of prostate cancer patients develop locally invasive and metastatic disease, with increased severity, limited treatment options, and the likelihood of death. For these individuals, easily accessible biomarkers that may inform on the metastatic potential of localized prostate cancer are urgently needed.

Investigators at Yale University (New London, CT, USA) are among those searching for such biomarkers. In this regard, they showed that syntaphilin (SNPH), a molecule originally identified as a negative regulator of mitochondrial dynamics in neurons, was abundantly expressed in prostate cancer. SNPH distribution in prostate cancer was found to be spatially biphasic, with high expression at the invasive front, correlating with increased proliferative rates, and reduced levels in the central tumor bulk, which were further decreased in patients with distant metastases.

Higher levels of SNPH were observed with increasing Gleason grade. The majority of treatable cancers are of Gleason scores five to seven, while tumors with Gleason scores eight to 10 tend to be advanced neoplasms that are unlikely to be cured.

The investigators also found that prostate tumors predominantly expressed a novel, extraneuronal isoform of SNPH that accumulated in mitochondria and maintained oxidative metabolism and tumor cell proliferation. Therefore, they speculated that SNPH could be a novel marker of high Gleason grade prostate cancer, differentially expressed at the invasive front compared with the central tumor bulk, and was potentially down regulated in the metastatic form of the disease.

"Predicting aggressive behavior in prostate cancer is an entirely unmet and urgent need. There are currently no tissue-based biomarkers to help clinicians reliably identify the subset of prostate cancer patients who will progress to life-threatening, disseminated disease and who would, therefore, benefit from systemic therapies before or following prostatectomy. If our findings are supported by larger studies, SNPH measurement in tumors could be developed into a predictive biomarker," said senior author Dr. Marie E. Robert, professor of pathology at Yale University. "This is the first study to suggest a clinical role for SNPH assessment in prostate cancer prognosis, potentially confirming recent evidence in experimental models of its importance in the phenotypic switch between proliferative and metastatic tumor states. Our results also reaffirm a critical, emerging role of mitochondrial biology in influencing tumor behavior."

The syntaphilin study was published in the May 9, 2019, online edition of The American Journal of Pathology.

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