Clinical Relevance of Circulating Nucleic Acids in Blood of Prostate Cancer Patients

Abstract

The prostate carcinoma is the most frequent cancer of men. In contrast to the second most lung cancer, there are no self-caused risk factors. Hence, the cause of prostate cancer is still unknown. Nevertheless, there are men having a higher risk to get prostate cancer than other men. In the early stage the disease is symptom-free, whereas in the advanced stage complaints, such as difficulty in urination, miction pains and bone pains may occur. If symptoms emerge, metastases, primarily in the local lymph nodes or the bone marrow, may frequently be diagnosed (Knudsen & Vasioukhin, 2010). A successive treatment is only possible if the tumour tissue did not metastasize. So far, the early diagnosis of prostate cancer is difficult and challenging. Usually, the diagnosis is associated with several prostate biopsies. The current standard screening method is carried out by measuring the level of the prostate specific antigen (PSA) in blood, combined with a digital rectal examination (Jones & Koeneman, 2008). However, in men starting from 50 years an increased PSA value can indicate benign prostatic hyperplasia or prostate cancer. Moreover, the increase in the blood level of PSA (biochemical recurrence) cannot differentiate between local and metastatic tumours (Jansen et al., 2008). Therefore, an increased PSA value has to be absolutely clarified. Moreover, most prostate tumours are initially sensitive to androgen ablation therapy. If the treatment is not curative, patients can become hormonal refractory. Although docetaxel-based chemotherapy remains the standard treatment for hormone-refractory prostate cancer (Tannock et al., 2004), few predictive factors for the efficacy of chemotherapy has been reported. Thus, new strategies of early prostate cancer diagnosis and prognosis should be developed. During the last years, nucleic acids, such as DNA, RNA and microRNAs (miRs), which circulate in high concentrations in blood of cancer patients, have gained increasing attention and their potential value as possible biomarkers has been highlighted. To avoid tumour biopsies by invasive methods, cell-free nucleic acids in plasma or serum could serve as a “liquid biopsy” useful for diagnostic application of prostate cancer. This minimally invasive procedure delivers the possibility of taking repeated blood samples, consequently allowing the changes in cell-free nucleic acids to be traced during the natural course of the disease or during anti-cancer treatment. The current chapter focuses on the clinical utility of cell-free nucleic acids as blood-based biomarkers for prostate cancer, considering the genetic and epigenetic alterations that can be detected in circulating DNA as well as the modulated levels of miRs. The relationship between cell-free nucleic acids and micrometastatic cells is also discussed.