Investigator
First Affiliated Hospital Of Zhengzhou University
Prognosis and fertility of stage II to IV borderline ovarian tumors after fertility-sparing surgery
To evaluate the prognosis and fertility of patients with stage II to IV borderline ovarian tumors who underwent fertility-sparing surgery. This retrospective single-institution study included patients aged <40 years with stage II to IV borderline ovarian tumors at the First Affiliated Hospital of Zhengzhou University between January 2007 and March 2023. The primary outcome was disease-free survival. The association of disease-free survival was assessed using the Kaplan-Meier and Cox proportional hazards methods. A total of 144 patients were included in this study. Based on whether fertility-sparing surgery was performed, the patients were categorized into 2 groups: a fertility-sparing surgery group with 96 patients (66.67%) and a radical surgery group with 48 patients (33.3%). There were differences between the 2 groups in terms of age (27.36 ± 6.42 vs 34.67 ± 5.43, p < .001), pregnancy history (53.1%; 51/96) vs 81.2% (39/48), p = .001), maximum tumor diameter (103.00 [76.25, 148.25] vs 88.50 [60.25, 124.75], p = .011), involvement of bilateral ovaries (45.83%; [44/96] vs 66.67% [32/48], p = .018), and whether postoperative adjuvant chemotherapy (15.6% [15/96] vs 31.2% [15/48], p = .030). The median follow-up time after primary cytoreduction was 67.0 months (interquartile range; 44.0-101.75). At the end of the observation period, 32 (22.2%) patients experienced recurrence. There were 3 (2.1%) deaths and 2 cases (1.4%) of survival with tumors. Multivariate Cox proportional hazards regression analysis showed that fertility-sparing surgery, incomplete cytoreduction, micropapillary subtype, International Federation of Gynecology and Obstetrics stage III, and invasive implants were independent risk factors for poor disease-free survival. Among the patients with fertility intentions (41 cases), 34 (82.9%) had successful pregnancies. Twenty-nine patients (70.7%) had successful births, and 3 patients were pregnant at the time of study completion. Fertility-sparing surgery may be feasible and considered for patients lacking other significant risk factors for disease-free survival, including incomplete cytoreduction, micropapillary subtype, International Federation of Gynecology and Obstetrics stage III, and invasive implants.
OTUD4-mediated inhibition of YAP1 signaling pathway in ovarian cancer: Implications for macrophage polarization and recruitment
Ovarian cancer is a malignancy gynecologic oncology with high incidence and high mortality rate. M2-like tumor-associated macrophages promote cancer cell migration and metastasis. Ovarian tumor family deubiquitinase 4 (OTUD4) belongs to deubiquitinating enzyme family. The roles of OTUD4 in tumor microenvironments in ovarian cancer remains unknow. In this work, OTUD4 was overexpressed or knocked down in high-grade serous ovarian cancer cells OVCAR8 and CAOV3. Ovarian cells were co-cultured with THP-1 macrophages to simulate the tumor microenvironment. We found that OTUD4-expressed ovarian cells inhibited macrophage chemotaxis and M2 polarization. Besides, in ovarian tumor-bearing mouse model, OTUD4 suppressed tumor metastasis and remodeling tumor-associated macrophages phenotype (pro-tumor M2 to anti-tumor M1). In mechanism, OTUD4 protein bound to YAP1 protein, and downregulation of OTUD4 enhanced K63 ubiquitination and nuclear translocation of YAP1, thus increasing CCL2 transcription and subsequent macrophage recruitment. OTUD4 might inhibit CCL2 expression to regulate tumor-associated macrophages in ovarian tumor microenvironment. Those findings present a potential therapeutic strategy for ovarian cancer.
Prevalence and prognostic role of PD-L1 in patients with gynecological cancers: A systematic review and meta-analysis
Our study aims to evaluate programmed cell death ligand-1 (PD-L1) expression and its prognostic significance in cervical cancer (CC), endometrial cancer (EC) and ovarian cancer (OC). Several electronic databases were searched. Fixed effects models or random effects models were employed to calculate the pooled prevalence of PD-L1 positivity and pooled hazard ratios (HRs) as appropriate. Heterogeneity and publication bias were also assessed. The pooled prevalence of PD-L1 positivity was 58.1%, 33.8% and 37.5% for CC, EC and OC patients, respectively. There were significant differences in the pooled estimates after stratification by PD-L1-positive assessment criteria and antibody clones. PD-L1 positivity was associated with worse OS in CC and EC patients and poorer progression-free survival (PFS) in CC patients. The prevalence of PD-L1-positive expression was considerably high in CC and modestly high in EC and OC patients. PD-L1 expression has the potential to be a prognostic biomarker for predicting the clinical outcomes of patients with CC and EC but not OC.
Expression of MCMs in Endometrial Cancer and its Biological Correlation Analysis
Purpose: Minichromosome maintenance (MCM) has been demonstrated to be involved in tumorigenesis and pathogenesis of many cancer types. However, the role of MCMs in endometrial cancer (EC) has not been elucidated. Materials and Methods: We first employed GEPIA, cBioPortal, and R software to perform the differential expression analysis, survival analysis, and gene alteration analysis of the MCMs family. Then, GSE17025 and GSE63678 datasets and CTPAC were used to verify the mRNA and protein expression levels of MCM4. In addition, the internal mechanism of the MCM4 was investigated by comparing MCM4 expression-correlated differentially expressed genes (DEGs) from GEPIA and MCM4-interacted genes from STRING. Last, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify MCM4-related biological processes. Results: Compared with normal tissues, only MCM2 and MCM4 expression were significantly upregulated in EC tissues. High expression of MCM4 was related to worse clinicopathological features and poor prognosis in EC cohorts. Additionally, a certain degree of gene alterations in the MCM2-7 gene was observed. By comparing MCM4 expression-correlated DEGs and MCM4- interacted genes, six genes were obtained: SSRP1, ORC1, GINS1, CDK2, DBF4 and GINS3. Functional enrichment analysis suggested that MCM4 may be involved in regulating the biological processes of DNA replication and the p53 signaling pathway. Conclusion: This was the first comprehensive study to disclose the biological effects of MCMs in EC, indicating that MCM4 could be used as a new prognostic biomarker and potential therapeutic target for EC.
Preoperative assessment of tumor size by MRI and ultrasound in cervical cancer: a large-scale retrospective comparative study
Abstract Purpose Accurate preoperative evaluation of tumor sizes is essential for guiding optimal treatment planning in cervical cancer. This study aimed to compare the accuracy of preoperative tumor size measurement between magnetic resonance imaging (MRI) and ultrasound. Methods A retrospective study was performed involving 925 patients diagnosed with cervical cancer who underwent primary surgical treatment between January 2020 and June 2025. The accuracy of these two imaging modalities was assessed by comparing their measurements to the maximum tumor diameter determined through postoperative pathological analysis. Results The Bland–Altman analysis showed that both ultrasound (mean difference: 1.50 mm) and MRI (mean difference: 0.61 mm) overestimated tumor size. In the paired subgroup of 757 patients who underwent both imaging modalities, the agreement rates between imaging and pathology for categorizing tumors into size groups were 65.8% for ultrasound and 67.6% for MRI ( p = 0.360). Although MRI showed a significantly smaller mean measurement bias than ultrasound (0.73 mm vs. 1.37 mm; p = 0.012), the proportion of large errors (> 10 mm) was not significantly different. Multivariate analysis indicated that tumors > 40 mm assessed by ultrasound (OR = 2.85) or MRI (OR = 2.72) were significantly associated with increased likelihood of measurement discrepancies > 10 mm. Conclusion While MRI exhibited a lower measurement error compared to ultrasound, both modalities showed comparable performance in tumor size staging. Furthermore, for tumors exceeding 40 mm in diameter as determined by preoperative imaging, clinicians are advised to integrate clinical examination to enhance the accuracy of staging.
Sentinel node mapping with carbon nanoparticles versus lymphadenectomy in early cervical cancer
To evaluate the morbidity of sentinel lymph node (SLN) biopsy with carbon nanoparticle suspension mapping compared to pelvic lymphadenectomy in patients with early-stage cervical cancer. This prospective study consecutively enrolled patients who were diagnosed pre-operatively with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB1 cervical cancer with histologically confirmed squamous-cell carcinoma or adenocarcinoma. Randomization was performed before surgery, and participants were assigned to undergo a SLN biopsy with carbon nanoparticle suspension (the biopsy group) or a pelvic lymphadenectomy (the lymphadenectomy group). The primary endpoint was lymph-related morbidity, and secondary endpoints included oncologic outcomes. A total of 208 patients were randomized to the biopsy group (104 cases) and the lymphadenectomy group (104 cases). Lymph-related complications, including lower extremity lymphedema (3.8% vs 19.2%, relative risk 0.20, 95% confidence interval [CI] 0.07 to 0.57, p < .01) and pelvic lymphoceles (18.3% vs 43.3%, p < .01), were significantly reduced in the biopsy group compared to the lymphadenectomy group. The incidence of neurological complications in the biopsy group, including those occurring during the peri-operative period and at the 6-month follow-up, and the occurrence of venous thrombosis, was significantly reduced (p < .05). In addition, the biopsy group demonstrated significantly shorter operative times (p < .01), lower pelvic drainage volumes (p < .01), shorter pelvic drainage times (p < .01), and decreased post-operative hospital stays (p = .02). Oncologic outcomes were comparable in the 2 groups, with the median follow-up of 18-month disease-free survival rates of 98.2% in the biopsy group and 95.2% in the lymphadenectomy group (hazard ratio 0.51, 95% CI 0.10 to 2.55, p = .42). SLN biopsy using carbon nanoparticle suspension as a substitute for pelvic lymphadenectomy can reduce post-operative morbidity, particularly lymph-related complications, with comparable short-term oncologic safety in FIGO stage IA2 to IB1 cervical cancer.
The application of PAX1 methylation detection and HPV E6/E7 mRNA detection in cervical cancer screening
AbstractAimWe aimed to explore the application of PAX1 methylation and human papillomavirus (HPV) E6/E7 mRNA detection in cervical cancer screening and to compare the efficacy with high‐risk (HR)‐HPV detection.Patients and methodsThe cervical exfoliative cytology samples of 337 patients were collected, including 70 cases of cervical inflammation, 72 cases of low‐grade squamous intraepithelial lesions, 97 cases of high‐grade squamous intraepithelial lesions, and 98 cases of cervical carcinoma. The PAX1 gene methylation (PAX1) status was detected by multiple quantitative PCR, HPV E6/E7 mRNA (E6/E7) was detected by QuantiVirus detection, and HR‐HPV (HPV) was detected by the Cobas 4800 detection system. The sensitivities, specificities, and accuracies were validated in the testing set.ResultsThe sensitivities of the HPV, HPV E6/E7, and PAX1 testing were 89.23%, 84.10%, and 86.67%, respectively, which all maintained a high level. In contrast, the specificities of the HPV, E6/E7, and PAX1 testing were only 19.10%, 37.32%, and 97.18% (in pairwise comparisons, p = 0.000). The AUC of PAX1 (0.919) was significantly larger than that of HPV (0.541) and E6/E7 detection (0.607) (p < 0.0001). In addition, the AUC areas of all combined parallel testing were lower than that of single PAX1 test (p < 0.05).ConclusionThe diagnostic efficacy of E6/E7 detection and PAX1 detection was better than that of HPV detection, especially for PAX1 detection.
