Haiyan Zhu

The prognostic values of matrix metalloproteinases in ovarian cancer

Objective To investigate the prognostic significance of 23 matrix metalloproteinase ( MMP) genes in patients diagnosed with ovarian carcinoma. Methods The prognostic significance of 23 MMP genes in patients diagnosed with ovarian carcinoma was investigated using the Kaplan–Meier plotter (KM plotter), which uses the gene expression data and overall survival information of patients with ovarian cancer that were downloaded from the Gene Expression Omnibus, Cancer Biomedical Informatics Grid and The Cancer Genome Atlas cancer datasets. The correlation between mRNA levels of individual MMPs (MMP2, MMP9, MMP10, MMP12, MMP13 and MMP25) and clinicopathological features (histological subtype, pathological grade and clinical stage) were investigated. The MMP protein level profiles in normal ovarian tissues and ovarian cancer tissues were examined using the Human Protein Atlas database. Results The results showed that high mRNA levels of MMP2 and MMP13 were associated with a worse overall survival in patients with ovarian cancer, whereas high mRNA levels of MMP9, MMP10, MMP12 and MMP25 were associated with a better overall survival. The protein levels of MMP2, MMP9, MMP10 and MMP25 in ovarian cancer tissues were elevated compared with normal ovarian tissues. Conclusions This study demonstrated that MMPs can be a reliable prognostic biomarker for ovarian cancer.

Comparative Survival Outcomes of Total Hysterectomy Versus Radical Hysterectomy in Gastric-Type Endocervical Adenocarcinoma: A SEER Database Analysis

This study aims to assess the efficacy of total hysterectomy versus radical hysterectomy in the treatment of gastric-type endocervical adenocarcinoma (GEA). Patients diagnosed with GEA from 2001 to 2021 were derived from the Surveillance, Epidemiology, and End Results database. Clinicodemographic characteristics, tumour clinicopathological features, and survival outcomes (including vital status and duration of follow-up) of these patients were collected. Kaplan-Meier survival curves were generated to estimate survival probabilities, with between-group differences assessed using log-rank tests for statistical significance. Overall, 114 patients undergoing total hysterectomy, and 129 patients undergoing radical hysterectomy were included for survival analysis. No statistically significant differences in overall survival (OS) were observed between surgical approaches, either in the entire cohort (P = 0.0594) or the International Federation of Gynecology and Obstetrics stage I-IIA subcohort (P = 0.0777). Adjuvant therapy (radiotherapy and/or chemotherapy) was administered to 52.6% (60/114) of patients in the total hysterectomy group and 42.6% (55/129) in the radical hysterectomy group. However, there was no statistically significant difference in OS between the total hysterectomy and radical hysterectomy groups among patients who received adjuvant therapy, and similar results were also found in the subgroup of patients with International Federation of Gynecology and Obstetrics stage Ⅰ-ⅡA disease. Notably, adjuvant therapies failed to demonstrate significant OS benefits in either surgical group for stage I-IIA disease. Total hysterectomy demonstrated comparable survival outcomes to radical hysterectomy in patients with GEA. These findings suggest that less extensive surgery may represent a viable treatment alternative for early-stage disease.

Predictive value of hemoglobin, platelets, and D-dimer for the survival of patients with stage IA1 to IIA2 cervical cancer: a retrospective study

Objective Coagulation indexes may be useful survival biomarkers for cervical cancer. This study evaluated the ability of hemoglobin, red blood cells (RBCs), platelets, and D-dimer levels to predict post-hysterectomy survival outcomes in patients with stage IA1 to IIA2 cervical cancer. Methods In this retrospective study, coagulation-related indexes were compared between the anemia and non-anemia groups. Independent variables were analyzed by the Cox proportional hazards model. Survival was assessed by the Kaplan–Meier method with the log-rank test. Mortality predictions were evaluated by receiver operating characteristic curves. Results Among this study’s 1088 enrolled patients, 152 had anemia. The 10-year overall survival and recurrence-free survival rates were 90.8% and 86.5%, respectively. Hemoglobin, RBC, and the rate of abnormal platelet counts were significantly lower in the anemia group. Abnormal preoperative D-dimer was an independent factor for recurrence-free survival. Receiver operating characteristic curves showed that D-dimer had area under the curve of 0.734 (cut-off value: 0.685, sensitivity: 85.7%, and specificity: 64.0%). Hemoglobin and platelets had areas under the curves of 0.487 and 0.462, respectively. Conclusion Preoperative D-dimer was the most effective prognostic predictor for patients with cervical cancer. The prognosis of patients with cervical cancer was poorer if their D-dimer levels were >0.685 mg/L.

Prognostic significance of poorly differentiated histology and impact of adjuvant chemotherapy in early squamous cell carcinoma of cervix uteri

AbstractObjectiveThis study is to determine whether the addition of cisplatin‐based chemotherapy after radical hysterectomy will improve the survival of low‐risk squamous cervical carcinoma with poor differentiation.MethodsPatients with low‐risk squamous cervical cancer (FIGO IA2–IIA, absent high‐ and intermediate‐risk factors after pathological evaluation) were eligible for this study. As first, the prognostic relevance of G3 versus G1/G2 among patients with low‐risk squamous cervical cancer was analyzed, then, the oncological results of postoperative chemotherapy among low‐risk squamous cervical cancer with poor differentiation was explored.ResultsTotally, there were 367 low‐risk squamous cervical cancer patients, of whom 161 were poor‐differentiated (47 in the chemotherapy group and 114 in the nonchemotherapy group), with a median follow‐up time of 56 months. Patients with G3 displayed a significantly worse overall survival (p = 0.035), and a higher recurrence rate (p = 0.014) than patients with G1/G2. Compared with the nonchemotherapy group, the hazard ratios (95%CI) for recurrence‐free survival in the chemotherapy group was 0.24 (0.06–0.93), (p = 0.038). No difference in overall survival was observed between the chemotherapy group and the nonchemotherapy group.ConclusionsThe addition of cisplatin‐based chemotherapy following surgery significantly improved recurrence‐free survival for low‐risk, poor differentiation, and early stage squamous cervical cancer patients.

Development of a nomogram for predicting pelvic lymph node metastasis in cervical squamous cell carcinoma

AbstractObjectiveTo develop and validate a nomogram for predicting pelvic lymph node metastasis (LNM) in cervical squamous cell carcinoma (SCC).MethodsThis was a retrospective study that included 715 patients with cervical SCC who underwent radical hysterectomy and bilateral pelvic lymphadenectomy between 2009 and 2018. Logistic regression analysis was used to identify independent risk factors for pelvic LNM. Based on these risk factors, a nomogram predicting LNM risk was constructed and internally validated using the bootstrapping resampling method.ResultsThe rate of LNM in FIGO (the International Federation of Gynecology & Obstetrics) Stage IA2–IIA2 cervical SCC was 24.2%. In multivariate analysis, FIGO Stage II, moderately differentiated or poorly differentiated histology, abnormally elevated serum SCC‐antigen, and triglyceride were identified as independent risk factors for LNM. Tumor size greater than 2 cm and parametrial involvement had borderline significance. Ultimately, the nomogram contained the six variables mentioned above, showing positive calibration and positive discrimination. The area under the receiver operating characteristic curvewas 0.827 and the bootstrap‐validated C‐index was 0.827. The Youden index of this paper was 0.540.ConclusionsWe developed and validated a nomogram to predict pelvic LNM in SCC based on clinical data, which can help physicians develop an optimal treatment strategy.

Comparison of recurrence patterns in cervical cancer patients with positive lymph nodes versus negative

AbstractPurposeThe aim of this study was to compare patterns of recurrence in 2009 FIGO Stage IB‐IIA (T1bN0M0‐T2aN0M0) cervical cancer patients with cN0 and cN1.MethodsThe epidemiological and clinical data of 1352 patients who had undergone radical hysterectomy and systematic lymphadenectomy with cervical cancer treated from January 2008 to April 2019 at a tertiary teaching hospital were retrospectively collected. The primary aim was to discover the lymph node status‐dependent patterns and time of recurrence.ResultsTumor recurrence and death were significantly less common in patients with cN0 than cN1. In addition, the length of time to recurrence (median 60 months cN0 vs. 43 months cN1, p < 0.001) and death (median 84 months cN0 vs. 68 months cN1 p < 0.001) were significantly longer in cN0 versus cN1 patients. The cumulative rate of relapse also showed a significant difference between cN0 and cN1 groups, especially the 1‐year relapse rate (2.14% vs. 10.78%). Of the patients who recurred, there was no difference in number of recurrent sites between cN0 and cN1 groups (solitary metastases:35.8% of cN0 and 35.6% of cN1; multiple metastases: 64.2% of cN0 and 64.4% of cN1). Similarly, there was no statistical difference in recurrence sites of cervical cancer between cN0 and cN1 groups based on three categories, (p = 0.646). However, in the six categories, patients' vaginal vaults with negative lymph nodes were more prone to recurrence, while the distribution of other recurrence sites showed no significant difference between the two groups.ConclusionsThere is a significant improvement of relapse‐free survival in the cN0 group, and the recurrence time of cN0 patients is significantly delayed than cN1 group. However, except for the risk of metastasis of the vaginal vault, the site of relapse remains similar.

Microbial and metabolic profiles associated with HPV infection and cervical intraepithelial neoplasia: a multi-omics study

ABSTRACT Cervical cancer is the most common malignancy of the female reproductive system, with the incidence of human papillomavirus (HPV) being a crucial factor in its pathogenesis. Emerging evidence indicates that cervicovaginal microbiota may influence HPV persistence and cervical intraepithelial neoplasia (CIN). However, the interplay between cervicovaginal and cervical tissue microbiomes and their association with HPV infection and CIN remains poorly understood. In this cross-sectional study, we analyzed the microbiota profiles of cervicovaginal and cervical tissue via five-region 16S rRNA gene metabarcoding, along with cervicovaginal metabolites, including short-chain fatty acids (SCFAs) and non-targeted metabolomic data, from 94 women. Key species, particularly Lacticaseibacillus and various anaerobes, are vital components of the microbiota found in both cervicovaginal secretions and cervical tissue, despite notable differences in microbial composition. The CIN group exhibited significant differences in microbial diversity and composition compared to the control groups, with key species such as Lacticaseibacillus iners and Prevotella bivia associated with HPV status and CIN progression. Metabolomic analysis revealed alterations in glycerophospholipid metabolism, but not in SCFAs, with correlations observed between metabolites and HPV status. Notable associations, including P. bivia –PE(18:1/0:0)–HPV and Fusobacterium periodonticum –PI(40:6)–HPV, were identified. Our findings emphasize the critical roles of cervicovaginal and cervical tissue microbiomes in HPV infection and CIN development, highlighting specific microbial species and metabolic pathways for early detection and therapeutic targets. IMPORTANCE Cervical cancer is the most prevalent malignancy in the female reproductive system, with human papillomavirus (HPV) persistency being a critical factor in its pathogenesis. This study highlights the significant yet often overlooked role of cervicovaginal secretion and cervical tissue microbiota in influencing HPV infection and the progression of cervical intraepithelial neoplasia (CIN). By employing a multi-omics approach, we elucidated distinct microbiota profiles in cervical tissues compared to cervicovaginal secretions, revealing a complex interplay between specific bacterial species (notably Lacticaseibacillus and anaerobes) and metabolomic changes associated with glycerophospholipid metabolism. Our findings address a significant gap in understanding the interplay between cervicovaginal secretion and cervical intratissue microbiomes, HPV infection, and CIN.