Shihong Cui

Analysis of the correlation between gut microbiome imbalance and the development of endometrial cancer based on metagenomics

Endometrial cancer (EC) is the most prevalent gynecologic malignancy, with a higher risk in obese women, suggesting the potential involvement of gut microbiota in the progression of EC. However, there is no direct evidence of a connection between EC and the human gut microbiota. Using metagenomic sequencing, we investigated the relationship between gut microbiome imbalance and cancer development in patients with EC. In this prospective case–control study, we included 15 patients with EC based on endometrial biopsy in the case group and 15 women admitted to the hospital for female pelvic floor issues during the same time who did not have endometrial lesions from January 2023 to June 2023 in control group. The microbiota structure of EC cases and controls without benign or malignant endometrial lesions during the same time period was analyzed using metagenomic sequencing technology. We employed Alpha diversity analysis to reflect the richness and diversity of microbial communities. Statistical algorithm Bray-Curtis was utilized to calculate pairwise distances between samples, obtaining a beta diversity distance matrix. Subsequently, hierarchical clustering analysis was conducted based on the distance matrix. The results showed that the composition of bacterial colonies in both groups was dominated by Firmicutes , which had a higher proportion in the control group, followed by Bacteroidetes in the control group and Proteobacteria and Bacteroidetes in the case group. The abundance of Klebsiella ( P  = .02) was significantly higher, and the abundance of Alistipes ( P  = .04), Anearobutyricum ( P  = .01), and bacteria in Firmicutes such as Oscillospira and Catenibacterium was markedly lower in the case group than in the control group. These results demonstrated conclusively that a gut microbiome imbalance was associated with the development of EC.

Gene Signatures and Prognostic Values of m6A RNA Methylation Regulators in Ovarian Cancer

Background: N6-methyladenosine (m6A) is the most common form of mRNA modification under the field of “RNA epigenetics.” However, its role in ovarian cancer (OC) development is poorly understood. In the current study, we aimed to identify gene signatures and prognostic values of m6A RNA methylation regulators. Method: Specifically, we downloaded Mutations and Copy number variant (CNV) data from the TCGA database for 579 OC patients, then analyzed gene expression and prognosis value using integrative bioinformatics. Thereafter, we verified the related biological processes of Wilms’ tumor 1-associating protein (WTAP) gene using Gene set enrichment analysis (GSEA). Results: Results showed that almost all ovarian cancer patients (99.31%) have CNVs with at least 1 m6A regulatory gene, whereas 83.76% of cases exhibited concurrence of CNVs in more than 4 m6A regulatory genes. Additionally, alteration of m6A regulators was associated with historical grade, whereas integrative bioinformatics and Cox multivariate model analysis revealed a significant correlation between high WTAP expression and worse ovarian cancer outcomes. Moreover, GSEA revealed that high WTAP expression was associated with cell cycle regulation and MYC targets. Conclusion: Overall, our findings demonstrate the significance of high-frequency genetic alterations of m6A RNA methylation regulators and WTAP’s poor prognosis value in OC. These findings provide valuable insights into the role of m6A methylation in OC, and will be vital in guiding development of novel treatment therapies.

Efficacy and safety of neoadjuvant chemotherapy versus primary debulking surgery in patients with ovarian cancer: a meta-analysis

Neoadjuvant chemotherapy (NACT) for the treatment of epithelial ovarian cancer (EOC) has remained controversial. This meta-analysis was performed to systematically assess the efficacy and safety of NACT versus primary debulking surgery (PDS) in patients with EOC. PubMed, Embase, ClinicalTrials.gov, and Cochrane Library were queried to assess the therapeutic value of NACT versus PDS in EOC. Electronic databases were queried by using the keywords "ovarian cancer/neoplasms", "primary debulking surgery", and "neoadjuvant chemotherapy". The available trials were pooled, and hazard ratios (HRs), relative risk ratios (RRs) and associated 95% confidence intervals (95% CIs) were determined. Sixteen trials involving 57,450 participants with EOC (NACT, 9,475; PDS, 47,975) were evaluated. We found that NACT resulted in markedly decreased overall survival than PDS in patients with EOC (HR=1.30; 95% CI=1.13-1.49; heterogeneity: p<0.001, I²=82.7%). Furthermore, our results demonstrated that the NACT group displayed increased completeness of debulking removal (RR=1.69, 95% CI=1.32-2.17; heterogeneity: p<0.001, I²=81.9%), and reduced risk of postsurgical death (RR=0.18, 95% CI=0.06-0.51; heterogeneity: p=0.698, I²=0%) and major infection (RR=0.29, 95% CI=0.17-0.51; heterogeneity: p=0.777, I²=0%) compared with patients administered PDS. This meta-analysis indicated that NACT results in increased completeness of debulking removal, and reduced risk of postsurgical death and major infection compared with PDS, while PDS is associated with improved survival in comparison with NACT in EOC patients. PROSPERO Identifier: CRD42019120625.