Dataset Information

An exploratory analysis of extracellular vesicle-associated and soluble cytokines in cancer-related fatigue in men with prostate cancer.

ABSTRACT:

Background

Cancer Related Fatigue (CRF) is one of the most prevalent and distressing symptoms associated with cancer treatments. The exact etiology of CRF and its mechanisms are poorly understood. Cytokine dysregulation was hypothesized to be one of these mechanisms. Here, we explored the associations of soluble and extracellular vesicle (EV)-associated markers that include cytokines, heat shock proteins (hsp27, hsp70, hsp90), and neurotrophic factors (BDNF) with CRF.

Methods

Plasma was collected from men (n = 40) with non-metastatic prostate cancer receiving external beam radiation therapy (EBRT) at the start of the treatment, and three months after EBRT. CRF was assessed using the Functional Assessment of Cancer Therapy - Fatigue (FACT-F) from all participants. EVs were characterized via Nanoparticle Tracking Analysis, electron microscopy, and Western blot. Concentrations of EV-associated and soluble markers were measured with a multiplexed immunoassay system. Bivariate correlation analyses and independent T tests analyzed the relationships of CRF with the markers.

Findings

As CRF worsened, concentrations of EV-associated markers were upregulated. EV-associated fold changes of Eotaxin, hsp27, IP-10, MIP-3α, were significantly higher in fatigued participants compared to non-fatigued EBRT participants three months after treatment. This was not observed in soluble markers. Concentrations of EV-associated CRP and MCP-1, soluble survivin, IFNα2, IL-8, IL-12p70, and MCP-1 significantly correlated with lower (worsening) CRF scores at the start of and three months after treatment.

Interpretation

Concentrations of EV-associated markers increased in fatigued men with prostate cancer three months after EBRT. Both EV-associated and soluble markers correlated with worsening CRF. EV-associated markers, which have not been previously studied in depth, may provide additional insights and serve as potential biomarkers for CRF.

SUBMITTER: Sass D

PROVIDER: S-EPMC8474622 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Because extracellular vesicle (EV)-associated cytokines, both encapsulated and surface bound, have been associated with symptom severity, and may vary over the lifespan, they may be potential biomarkers to uncover underlying mechanisms of various conditions. This study evaluated the associations of soluble and EV-associated cytokine concentrations with distinct symptom profiles reported by 290 women with breast cancer prior to surgery. Patients were classified into older (≥60 years, n = 93) and younger (< 60 years, n = 197) cohorts within two previously identified distinct symptom severity profiles, that included pain, depressive symptoms, sleep disturbance, and fatigue (i.e., High Fatigue Low Pain and All Low). EVs were extracted using ExoQuick. Cytokine concentrations were determined using Luminex multiplex assay. Mann Whitney U test evaluated the differences in EV and soluble cytokine levels between symptom classes and between and within the older and younger cohorts adjusting for Karnofsky Performance Status (KPS) score, body mass index (BMI), and stage of disease. Partial correlation analyses were run between symptom severity scores and cytokine concentrations. Results of this study suggest that levels of cytokine concentrations differ between EV and soluble fractions. Several EV and soluble pro-inflammatory cytokines had positive associations with depressive symptoms and fatigue within both age cohorts and symptom profiles. In addition, in the older cohort with High Fatigue Low Pain symptom profile, EV GM-CSF concentrations were higher compared to the All Low symptom profile (p < 0.05). Albeit limited by a small sample size, these exploratory analyses provide new information on the association between cytokines and symptom profiles of older and younger cohorts. Of note, unique EV-associated cytokines were found in older patients and in specific symptom classes. These results suggest that EVs may be potential biomarker discovery tools. Understanding the mechanisms that underlie distinct symptom class profiles categorized by age may inform intervention trials and offer precision medicine approaches.