1.Gut microbiome associated with PARP inhibitor efficacy in patients with ovarian cancer
Mika OKAZAWA-SAKAI ; Shunsuke A. SAKAI ; Ichinosuke HYODO ; Satoshi HORASAWA ; Kentaro SAWADA ; Takao FUJISAWA ; Yasuko YAMAMOTO ; Shogen BOKU ; Yoh HAYASAKI ; Masanori ISOBE ; Daisuke SHINTANI ; Kosei HASEGAWA ; Tomomi EGAWA-TAKATA ; Kimihiko ITO ; Kei IHIRA ; Hidemichi WATARI ; Kazuhiro TAKEHARA ; Hiroshi YAGI ; Kiyoko KATO ; Tatsuyuki CHIYODA ; Kenichi HARANO ; Yoshiaki NAKAMURA ; Riu YAMASHITA ; Takayuki YOSHINO ; Daisuke AOKI
Journal of Gynecologic Oncology 2025;36(3):e38-
Objective:
To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer.
Methods:
This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing.
Results:
Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11–0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016).
Conclusion
High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.
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