Plasma trimethylamine N-oxide and related metabolites and overall survival of high-grade serous ovarian cancer: a nested case-control study.

PURPOSE: The objective was first to investigate the associations between plasma levels of trimethylamine N-oxide (TMAO) and related metabolites [choline, betaine, L-carnitine, methionine, dimethylglycine (DMG)] and overall survival (OS) in patients diagnosed with high-grade serous ovarian cancer (HGSOC).

METHODS

A nested case-control study was conducted within the Ovarian Cancer Follow-Up Study. The study included 159 pairs of deceased and surviving patients, matched by age at diagnosis, body mass index, and sample date. The plasma levels of TMAO and related metabolites at baseline were measured using a liquid chromatography system coupled with tandem mass spectrometry. Multivariable conditional logistic regression models were employed to estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs).

RESULTS

The elevated plasma TMAO levels in the highest tertile were significantly associated with poorer OS of HGSOC in the multivariate-adjusted model (OR = 2.05, 95%CI = 1.11-3.78). Conversely, high levels of choline, betaine, methionine, and total methyl donors exhibited a positive association with improved OS of HGSOC [ORs and 95%CIs (Tertile 3 vs. Tertile 1): 0.51 (0.27-0.95), 0.49 (0.25-0.97), 0.40 (0.21-0.76), and 0.26 (0.13-0.54), respectively]. Significant dose-response relationships with OS in HGSOC were also observed for these exposures. However, no associations were observed between L-carnitine, DMG, Betaine/Choline, DMG/Choline, and DMG/Betaine with OS in HGSOC.

CONCLUSION

Elevated plasma TMAO levels were associated with poor OS of HGSOC. While increased levels of choline, betaine, methionine, and total methyl donors were related to an improved OS of HGSOC.