Plasma Exosomal AKR1C3 mRNA Expression Is a Predictive and Prognostic Biomarker in Patients with Metastatic Castration-Resistant Prostate Cancer

Abstract

Purpose Aldo-keto reductase family 1 member C3 (AKR1C3) is important in prostate cancer progression, being a potential biomarker in metastatic castration-resistant prostate cancer (mCRPC). Previous explorations of AKR1C3 are mainly based on tissue samples. This study investigates using plasma-based liquid biopsy to validate the prognostic and predictive value of AKR1C3 in patients with mCRPC . Materials and Methods We prospectively recruited 62 patients with mCRPC. All patients received repeated prostate biopsies at the time of mCRPC diagnosis, and immunohistochemistry (IHC) staining was used to detect protein expression of AKR1C3 in the tissues. We took their blood simultaneously and performed digital droplet polymerase chain reaction (ddPCR) to measure expression levels of AKR1C3 in the exosomes. The detected plasma and tissue AKR1C3 expression levels were analyzed for patients’ overall survival (OS) and progression-free survival under first-line abiraterone use (ABI-PFS). Results All other baseline characteristics were balanced between the 2 groups. 15/62 (24.2%) and 25/62 (40.3%) patients showed AKR1C3-EXO positive (≥20 copies/20 μL) and AKR1C3-IHC positive, respectively. Positive AKR1C3-EXO expression was associated with decreased patients’ survival [ABI-PFS: 3.9 vs 10.1 months, P < .001; OS: 16.2 vs 32.5 months, P < .001]. AKR1C3-IHC positivity was also correlated with ABI-PFS and OS (P = .010, P = .016). In patients with worse baseline blood tests (including higher alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) level and lower hemoglobin (HB) level), and lower ISUP/WHO group (<4), their OS was significantly worse when showing AKR1C3-EXO positive. Conclusion AKR1C3-EXO is associated with patient prognosis regarding OS and ABI-PFS and can be used as a biomarker in mCRPC.

AKR1C3 promotes progression and mediates therapeutic resistance by inducing epithelial-mesenchymal transition and angiogenesis in small cell lung cancer

“…In liver cancer, high AKR1C3 expression is associated with a significantly poorer prognosis [ 37 ]. Studies have suggested that AKR1C3 expression levels in tissues or plasma exosomes could serve as prognostic markers for patients with castration-resistant prostate cancer [ 38 ]. Elevated AKR1C3 expression was found to be correlated with a worse prognosis in patients with oral squamous cell carcinoma and esophageal adenocarcinoma [ 39 , 40 ].…”

Role of exosomes in non-small cell lung cancer and EGFR-mutated lung cancer

“…In this context, the identification of subclasses of extracellular vesicles derived from cancer cells and microenvironmental components associated with well-defined pathological processes would allow them to serve as complementary biomarkers of circulating cfDNA and circulating tumor cells. In recent years, several studies have demonstrated the value of exosomes as cancer biomarkers, allowing longitudinal monitoring of tumor heterogeneity and early identification of cancer subtypes ( 154 , 155 ), as well as monitoring microenvironmental subversion ( 156 ), tumor progression and prognostic decisions ( 157 ), and response to therapy to tailor therapeutic interventions ( 158 , 159 ). Further developments in this field will bring us closer to the most important goal of providing personalized cancer care.…”

Perspective Chapter: Clinical Application of Exosome Components

“…Another study reported that the urine exosomes integrin alpha-3 (ITGA3) and integrins beta-1 (ITGB1) in metastatic PCa patients were higher than PCa and benign prostatic hyperplasia (BPH) [46]. Plasma exosomal aldo-keto reductase family 1 member C3 (AKR1C3) have also been demonstrated to be associated with the OS of PCa patient, which is recognized to be a potential prognostic biomarker for PCa [47]. Furthermore, Krishn et al demonstrated that αvβ3 integrin was transferred to β3-negative recipient cells by exosomes derived from PCa patient plasma and can be identified as a therapeutic target for PCa [48].…”