Okazawa-Sakai Mika, Sakai Shunsuke A, Hyodo Ichinosuke, Horasawa Satoshi, Sawada Kentaro, Fujisawa Takao, Yamamoto Yasuko, Boku Shogen, Hayasaki Yoh, Isobe Masanori, Shintani Daisuke, Hasegawa Kosei, Egawa-Takata Tomomi, Ito Kimihiko, Ihira Kei, Watari Hidemichi, Takehara Kazuhiro, Yagi Hiroshi, Kato Kiyoko, Chiyoda Tatsuyuki, Harano Kenichi, Nakamura Yoshiaki, Yamashita Riu, Yoshino Takayuki, Aoki Daisuke
Department of Gynecologic Oncology, NHO Shikoku Cancer Center, Matsuyama, Japan.
Department of Cancer Genomic Medicine, NHO Shikoku Cancer Center, Matsuyama, Japan.
J Gynecol Oncol. 2025 May;36(3):e38. doi: 10.3802/jgo.2025.36.e38. Epub 2024 Oct 21.
To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer.
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 / mutation (/mut) status detected by ctDNA sequencing.
Baseline samples were available from 23 /mut-positive patients and 33 mut-negative patients. The microbes enriched in the baseline samples with long PFS were , , , , and for mut-positive patients and for mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in mut-positive patients, whereas high abundances (≥1.11%) was significantly associated with longer PFS in mut-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 were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016).
High fecal composition of was associated with prolonged PFS in patients with mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.
探讨肠道微生物群与聚（ADP - 核糖）聚合酶抑制剂（PARPi）治疗卵巢癌疗效之间的关联。
本研究对接受PARPi维持治疗的卵巢癌患者进行了粪便微生物群分析（16S rRNA基因测序）和循环肿瘤DNA（ctDNA）分析。在基线以及疾病进展（PD）或最后一次随访时采集粪便和血液样本。根据ctDNA测序检测到的/突变（/mut）状态，使用效应大小的线性判别分析和Cox比例风险模型分析肠道微生物的相对丰度和无进展生存期（PFS）。
有23例/mut阳性患者和33例mut阴性患者的基线样本可供分析。在PFS较长的基线样本中富集的微生物，/mut阳性患者为、、、、，mut阴性患者为。在根据相对丰度中位数对患者进行划分的多变量分析中，/mut阳性患者中没有细菌与PFS相关，而高丰度（≥1.11%）与mut阴性患者更长的PFS显著相关（中位数14.0个月对5.9个月，风险比=0.28；95%置信区间=0.11 - 0.69；p = 0.014）。在最后一批样本中，无PD患者（n = 5）的相对丰度显著高于有PD患者（n = 15）（中位数1.25%对0.06%；p = 0.016）。
接受PARPi治疗的mut阴性卵巢癌患者粪便中高含量与PFS延长相关。我们的结果将为未来研究提供新的见解。
