Alpha Satellite RNA Levels Are Upregulated in the Blood of Patients with Metastatic Castration-Resistant Prostate Cancer

Abstract

The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker.

Keywords: alpha satellite DNA; alpha satellite RNA; blood biomarker; prostate cancer; transcription.

Figure 1

The level of intracellular alpha satellite RNA from the whole blood of control healthy individuals and of prostate cancer patients belonging to groups: A—metastatic hormone-sensitive on treatment; B—metastatic castration-resistant on treatment; C—localised hormone-sensitive on treatment; D—localised hormone-sensitive before any treatment. RNA level is obtained by RT-qPCR and the normalised average no value for each sample was used. Differences are analysed by 2-tailed Welch’s t test for groups A, B, and the control, and Mann–Whitney for group C and group D; median values are indicated and error bars represent standard deviations. Statistically significant differences of group B relative to groups A, C, D, and the controls, respectively, are indicated by stars (*** denotes p < 10⁻³, ** p < 10⁻², * p < 0.05).

Figure 2

The diagnostic potential of alpha satellite RNA levels is determined by computing ROC curves and quantifying AUC values. The alpha RNA level shows the highest discriminatory power for distinguishing group B metastatic castration-resistant prostate cancer from: controls (AUC 0.848); group C (AUC 0.853); group A (AUC 0.744); and group D (AUC 0.717).

Figure 3

LogPSA values in the blood of control healthy individuals and of prostate cancer patients belonging to groups: A—metastatic hormone-sensitive on treatment; B—metastatic castration-resistant on treatment; C—localised hormone-sensitive on treatment; D—localised hormone-sensitive before any treatment. Differences between groups are analysed by Mann–Whitney and Kruskal–Wallis statistical tests, and median values are indicated and error bars represent standard deviations. Statistically significant differences of control relative to groups A, B. and D, respectively, are indicated by stars (**** denotes p < 10⁻⁴, ns means not significant).