Expression of hypoxia proteins indicates cancer recurrence after prostatectomy
MedWire News: Researchers have identified two potential novel biomarkers associated with hypoxia which may have implications for the prognosis of men with prostate cancer who have undergone radical prostatectomy.
Study results show that the upregulation of glucose transportation (eg, GLUT1), and the prolyl-4-hydroxylase 1 (PHD1) protein, both linked to the Hypoxia Inducible Factor (HIF-1α) pathway, significantly correlated with a shorter time to biochemical disease recurrence in such men.
“Low tissue oxygen pressure (hypoxia) is a common characteristic of cancers from different sites, including prostate cancer, and is often associated with disease progression,” explain Judith Jans, from University Medical Center in Utrecht, The Netherlands, and colleagues.
The researchers studied radical prostatectomy tissue samples from 71 patients. Of the patients, 32% developed biochemical recurrence during a median follow-up time of 62 months.
Samples were analyzed using a microarray test which revealed the expression of HIF-1α as well as GLUT1, confirming the presence of hypoxia and activation of the entire HIF-1α pathway.
Univariate analysis showed that Gleason score, clinical T stage, and having a positive surgical margin correlated significantly with time to biochemical recurrence.
In multivariate analysis, adjusting for patient Gleason score, T stage, and tumor margin status, the presence of GLUT1 predicted a 6.6 times shorter time to biochemical recurrence compared with an absence of GLUT1.
“Patients with elevated levels of GLUT1 have a significantly shorter time to biochemical recurrence after radical prostatectomy,” note Jans and team in the journal Urology.
They add, “Whether GLUT1 overexpression indicates a poor prognosis in prostate cancer patients was until now unknown.”
In addition, the nuclear location of PHD1 in prostate cancer cells significantly correlated with time to biochemical recurrence in univariate analysis.
To investigate whether the nuclear localization of PHD1 was a direct consequence of the hypoxic environment, the researchers cultured prostate cancer cell lines under normoxic and hypoxic conditions. PHD1 localized to the nucleus in both scenarios.
This observation “suggests that [PHD1] may be an important, separate step in the progression of prostate cancer,” write Jans et al.
They conclude: “Further studies on expression of other glucose transporters within the GLUT1 protein family in prostate cancer may provide additional insight into the prognostic significance of the metabolic state of prostate cancer cells.”
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By Sarah Guy