Abstract
Incidence rates for endometrial cancer (EC) are rising, particularly in postmenopausal and obese women. Previously, we showed that the uterine and vaginal microbiome distinguishes patients with EC from those without. Here, we sought to examine the impact of patient factors (such as menopause status, body mass index, and vaginal pH) in the microbiome in the absence of EC and how these might contribute to the microbiome signature in EC. We find that each factor independently alters the microbiome and identified postmenopausal status as the main driver of a polymicrobial network associated with EC (ECbiome). We identified Porphyromas somerae presence as the most predictive microbial marker of EC and we confirm this using targeted qPCR, which could be of use in detecting EC in high-risk, asymptomatic women. Given the established pathogenic behavior of P. somerae and accompanying network in tissue infections and ulcers, future investigation into their role in EC is warranted.
Highlights
Endometrial cancer (EC) is the most common gynecological malignancy in the United States and the fourth most common cancer among women[1,2]
endometrial cancer (EC) patients were significantly more likely to have a high vaginal pH (>4.5, p < 0.001), which is consistent with our previous report[22]
To evaluate whether our findings may extend to Type II EC, and precancerous transformations, we investigated the distribution of the 17 EC enriched operational taxonomic units (OTUs) in these subgroups (9 patients with Type II EC and 7 patients with complex hyperplasia with atypia)
Summary
Endometrial cancer (EC) is the most common gynecological malignancy in the United States and the fourth most common cancer among women[1,2]. It is thought that postmenopausal women with a high body max index (BMI) are at an increased risk for Type I EC because of higher plasma estrogen[6]. Type II EC develops in a background of endometrial atrophy, but hormonal risk factors are unknown, making early identification and treatment important to improved patient prognosis[5,7]. Type II EC is less likely to manifest early through postmenopausal bleeding, and is more common among Black women[8], contributing to the existing health disparities in the disease outcome[9]. Previous studies have demonstrated that microorganisms play important roles in cancer causation and development, ranging from cervical cancer[10] to gastrointestinal malignancies[11]. We provide an in-depth examination of the influence of EC risk factors on the microbiome, correlate those with microbes enriched in EC, and evaluate the translational potential of these findings
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