Biomarkers for Prostate Cancer Bone Metastasis Detection and Prediction

Abstract

Prostate cancer (PCa) causes deaths worldwide, ranking second after lung cancer. Bone metastasis (BM) frequently results from advanced PCa, affecting approximately 90% of patients, and it also often results in severe skeletal-related events. Traditional diagnostic methods for bone metastases, such as tissue biopsies and imaging, have substantial drawbacks. This article summarizes the significance of biomarkers in PCa accompanied with BM, including (1) bone formation markers like osteopontin (OPN), pro-collagen type I C-terminal pro-peptide (PICP), osteoprotegerin (OPG), pro-collagen type I N-terminal pro-peptide (PINP), alkaline phosphatase (ALP), and osteocalcin (OC); (2) bone resorption markers, including C-telopeptide of type I collagen (CTx), N-telopeptide of type I collagen (NTx), bone sialoprotein (BSP), tartrate-resistant acid phosphatase (TRACP), deoxypyridinoline (D-PYD), pyridoxine (PYD), and C-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP); (3) prostate-specific antigen (PSA); (4) neuroendocrine markers, such as chromogranin A (CgA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (ProGRP); (5) liquid biopsy markers, such as circulating tumor cells (CTCs), microRNA (miRNA), circulating tumor DNA (ctDNA), and cell-free DNA (cfDNA) and exosomes. In summary, some of these markers are already in widespread clinical use, while others still require further laboratory or clinical studies to validate their value for clinical application.

The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery

“…Furthermore, PINP was correlated with survival in prostate cancer patients with bone metastasis [131,132]. Increased blood levels of PYD, D-PYD [123], and ICTP [130] were also found in individuals with prostate cancer bone metastasis. Higher PYD levels were linked to worse overall survival [133], while ICTP was shown to be a useful biomarker for prostate cancer bone metastasis, especially when combined with other biomarkers [134].…”

“…It is estimated that about 70-90% of prostate cancer patients with advanced disease will develop bone metastasis (usually homed in the axial skeleton of the pelvis or spine) that is frequently accompanied by intolerable bone pain that lowers life quality and impairs overall survival [123,124]. However, bone metastases are challenging to detect before their final stages.…”

“…The biomarker potential of PINP, PICP, CTx, NTx, ICTP, PYD, and D-PYD in prostate cancer has been extensively reviewed [123][124][125][126][127][128][129]. Briefly, bone metastases were repeatedly shown to increase PINP and PICP levels in the serum of prostate cancer patients [123], and the rise in levels of PINP in the serum is a sign of prostate cancer bone metastasis progression [130]. Furthermore, PINP was correlated with survival in prostate cancer patients with bone metastasis [131,132].…”

“…Taken together, these studies suggest that bone turnover proteins from the pathway of collagen synthesis and breakdown have biomarker potential in prostate cancer bone metastasis diagnosis but also bear prognostic value since they are correlated with the survival of prostate cancer patients. Other bone formation (BGLAP (osteocalcin) and SPP1 (osteopontin)) and bone resorption (IBSP (integrin-binding sialoprotein or bone sialoprotein)) ECM glycoproteins were also explored for their biomarker potential in prostate cancer metastasis formation and are discussed in more detail in [123]. Briefly, further research is required to define their potential biomarker roles.…”

Complications prevention of bone metastases in prostate cancer

“…Entre los datos de laboratorio, es habitual encontrar niveles elevados de PSA sérico (> 10 ng/ml), aumento de la fosfatasa alcalina sérica y anemia. En el caso de tumores de próstata pobremente diferenciados y con un Gleason elevado, sin embargo, no es raro encontrar valores de PSA < 10 ng/ml o incluso menores, lo que no excluye la posible presencia de metástasis óseas (11).…”