Biobehavioral factors predict an exosome biomarker of ovarian carcinoma disease progression

Cancer. 2022 Dec 1;128(23):4157-4165. doi: 10.1002/cncr.34496. Epub 2022 Oct 17.

Abstract

Background: Biobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors.

Methods: Exosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were analyzed by elastic net machine learning to identify a biomarker predicting rapid (≤6 months) versus more extended disease-free intervals following initial treatment. Samples from a second subgroup of 24 patients were analyzed by mixed-effects linear models to determine whether the progression-predictive biomarker varied longitudinally as a function of biobehavioral risk factors (social isolation and depressive symptoms).

Results: An RNA-based molecular signature was identified that discriminated between individuals who had disease progression in ≤6 months versus >6 months, independent of clinical variables (age, disease stage, and grade). In a second group of patients analyzed longitudinally, social isolation and depressive symptoms were associated with upregulated expression of the disease progression propensity biomarker, adjusting for covariates.

Conclusion: These data identified a novel exosome-derived biomarker indicating propensity of ovarian cancer progression that is sensitive to biobehavioral variables. This derived biomarker may be potentially useful for risk assessment, intervention targeting, and treatment monitoring.

Keywords: biobehavioral; exosome; ovarian cancer; progression; social support; transcriptome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Carcinoma*
  • Carcinoma, Ovarian Epithelial
  • Disease Progression
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Female
  • Humans
  • Ovarian Neoplasms* / pathology
  • RNA / metabolism
  • RNA / therapeutic use

Substances

  • Biomarkers
  • RNA