Purpose: Ovarian cancer (OC) is a highly lethal gynecological malignancy, characterized by high recurrence and platinum-based chemotherapy resistance. While the gut microbiome's role in tumor progression and therapy is a major research focus, its connection to extra-intestinal cancers, particularly OC, remains unclear. Current studies on the OC microbiome are incomplete, with a lack of biomarkers for early diagnosis and distinguishing platinum-sensitive from platinum-resistant cases. This study aims to explore the correlation between chemotherapy resistance in OC and the fecal microbiome.
Sample and setting: We collected fecal samples from six platinum-sensitive and three platinum-resistant OC patients. The clinical characteristics of all participants were assessed. Next-generation metagenomic sequencing (mNGS) was used to characterize the gut microbiome, allowing comparisons and identification of different microbiome types.
Procedures: MetagenomeSeq analysis was employed, and the Linear Discriminant Analysis Effect Size (LEfSe) was used to assess species abundance. Functional predictions of the microbiome were performed using the STAMP software. The "psych" package was utilized to study the relationship between gut microbiome and clinical variables. Additionally, we investigated the effects of Veillonella on the malignant phenotypes of OC cells through cytological experiments.
Results: Our study showed that, compared to the platinum-sensitive group, the key microbiome abundance in the platinum-resistant group was significantly reduced. LEfSe analysis revealed notable differences in the fecal microbiome between platinum-sensitive and platinum-resistant OC patients. In the platinum-resistant group, the abundance of Spirochaetaceae, Spirochaetales, and Bifidobacterium was decreased, while the abundance of Streptococcus, Streptococcus pyogenes, and Firmicutes increased. Veillonella parvula was found to be significantly positively correlated with platinum resistance. Cytological experiments demonstrated that Veillonella parvula promoted OC cell proliferation, migration, invasion, and platinum resistance.
Conclusion and clinical implications: Our findings suggest that the fecal microbiome, particularly Veillonella, holds promise as a potential biomarker for assessing platinum sensitivity in OC patients.