A specific colonization of pathogenic microbes in the reproductive tract may be commonly found in patients with ovarian cancer, according to a new study published by Asangba et al in Scientific Reports. The discovery strengthens evidence that the bacterial component of the microbiome may be an important indicator for the early detection, diagnosis, and prognosis of ovarian cancer.
Background
Ranking fifth in cancer mortality among female patients, ovarian cancer is the second most common gynecologic malignancy. According to the American Cancer Society, experts have estimated that 20,000 individuals in the United States may be diagnosed with ovarian cancer in 2023, and nearly 13,000 may die from the disease.
Most individuals who are affected are usually diagnosed at an advanced stage because early-stage disease is usually asymptomatic. Furthermore, only 20% of cases are caused by genetic mutations—including BRCA1 and BRCA2 genes—while the remaining 80% of cases have no known cause.
Zeroing in on Pathogenic Microbes
In the new study, researchers compared samples from 30 patients undergoing a hysterectomy for ovarian cancer with samples from 34 patients undergoing a hysterectomy for a benign condition. They used high-throughput sequencing to analyze the samples recovered from the lower and upper reproductive tract, peritoneal fluid, urine, and the anal microbiome. Among the patients with ovarian cancer, the researchers observed a colonization of disease-causing bacteria—including Dialister, Corynebacterium, Prevotella, and Peptoniphilus.
"These microbes are known to be associated with other diseases—including other cancers—but more [studies are] needed to know if they are a contributing driver of ovarian cancer," underscored study author Marina R. Walther-Antonio, PhD, Assistant Professor of Surgery in the Department of Obstetrics and Gynecology as well as a microbiome researcher at the Center for Individualized Medicine at the Mayo Clinic.
"In addition, we found a clear pattern that reveals [individuals] with early-stage ovarian cancer have a significantly higher accumulation of the pathogenic microbes when compared to [patients] with later-stage disease," stressed lead study author Abigail E. Asangba, PhD, a postdoctoral research fellow in the Department of Surgery as well as a microbiome researcher at the Center for Individualized Medicine at the Mayo Clinic. "In later stages, the number of microbes fades. This strong signal could potentially help us diagnose [patients] earlier and save lives—similar to how a noninvasive Pap smear is used to detect cervical cancer,” she noted.
The study also suggested that a higher accumulation of pathogenic microbes may play a role in treatment outcomes and could be a potential indicator for predicting a patient's prognosis and response to therapy. “We analyzed whether patients with similar outcomes also had a similar microbial composition before they started treatment, irrespective of stage, grade, or histology of cancer, as well as other factors. We found that the patients with a higher accumulation of pathogenic microbes had poorer outcomes in comparison to those without," Dr. Asangba explained.
Conclusions
"Our ultimate goal is to understand what role the microbiome plays in gynecologic cancers. We are exploring several potential avenues: the role in the causation of the disease, aggravation of the disease, and treatment resistance," said Dr. Walther-Antonio.
The new study is an extension of several previous studies linking the microbiome to endometrial cancer. In one study—published by Crooks et al in Frontiers in Microbiology—researchers found that the microbe Porphyromonas somerae had a pathogenic role in endometrial cancer via intracellular activity.
Dr. Walther-Antonio noted that identifying microbiome signatures to predict the development of malignancies could lead to intervention before cancers have a chance to materialize. "Our latest study provides a significant leap toward understanding the prognostic potential of the microbiome and places us a step closer to being able to help our patients," he concluded.
Disclosure: The research in this study was supported by a career development award from the Mayo Clinic Ovarian Cancer Specialized Program of Research Excellence—made possible by a grant from the National Institutes of Health—as well as the Minnesota Ovarian Cancer Alliance, and a Clinical and Translational Science Awards program grant from the National Center for Advancing Translational Sciences. For full disclosures of the study authors, visit nature.com.
