西尾 永司

Abstract Currently, human papillomavirus tests and cytology are used to screen for cervical cancer. However, more accurate ancillary screening tests are needed. MicroRNAs (miRNAs) and cytokines are promising biomarkers that are aberrantly expressed in cervical cancer. Therefore, the potential of developing new screening markers based on the levels of miRNAs and cytokines in serum and local mucus samples from the same patients with cervical neoplasia was investigated. miRNA screening was performed by microarray and measurement using real‐time reverse‐transcriptase PCR. Cytokine were measured using multiplex bead assay, and changes in expressions were analyzed based on disease severity. As lesions progressed, miR‐20b‐5p, −155‐5p, −144‐3p, −451a, and −126‐3p expression levels were increased in mucus, and miR‐16‐5p, −223‐3p, and ‐451a expression levels were decreased in serum. Regarding cytokines, IL‐6, IL‐8, monocyte chemoattractant protein‐1, Eotaxin, interferon‐γ, and RANTES were increased, whereas granulocyte–colony‐stimulating factor (G‐CSF) was significantly decreased in mucus. miRNAs and cytokines in serum did not have high diagnostic accuracy. However, a combination of miR‐20b‐5p, ‐451a, ‐126‐3p, Eotaxin, as well as G‐CSF in mucus samples, had high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.989 (0.979–0.999). Our results suggest that using mucus for this ancillary test is more beneficial than serum.

Abstract Purpose In the context of in vitro fertilization–embryo transfer (IVF–ET), factors other than egg quality may be key determinants of treatment success, in particular, maternal factors related to uterine endometrial receptivity and unidentified factors. We therefore aimed to analyze the metabolome and microbiome in IVF–ET patients who did and did not achieve pregnancy. Methods Cervicovaginal mucus was collected from patients undergoing IVF–ET. Metabolite analysis was conducted by liquid chromatography‐mass spectrometry and the microbiota were determined by the polymerase chain reaction using universal 16S‐rRNA gene bacterial primers by MiSeq sequencing. Patients were classified as pregnant (N = 10) or nonpregnant (N = 13). Metabolic pathways were examined by MetaboAnalyst. Results Three metabolic pathways, including alanine‐aspartate–glutamate metabolism, arginine biosynthesis, and cysteine‐methionine metabolism, were commonly decreased at the time of embryo transfer irrespective pregnant outcomes. Notably, pyruvate was decreased in the pregnant group. Amino acid metabolites showed inverse correlations with the presence of anaerobic microbiota in the nonpregnant group. Conclusions Metabolism decreased during embryo transplantation, with a notable decrease in pyruvate metabolism, particularly in patients who became pregnant. The behavior of metabolites in the pregnant and nonpregnant groups suggests that metabolome analysis in the cervicovaginal mucus may be a diagnostic marker for predicting pregnancy.