Sufang Wu’s research while affiliated with Shanghai Jiao Tong University and other places

Background The increasing problems of drug and radiotherapy resistance in cervical cancer underscores the need for novel methods for its management. Reports indicate that the expression of MPC1 may be associated with the tumor microenvironment and the occurrence of ferroptosis in cervical cancer. The objective of this study was to visually illustrate the prognostic significance and immunological characterization of MPC1 in cervical cancer. Methods The expression profile and prognostic significance of MPC1 were analyzed using various databases, including UALCAN, TIMER2, GEPIA2, and Kaplan–Meier Plotter. TISIDB, TIMER2, and immunohistochemical analysis were used to investigate the correlation between MPC1 expression and immune infiltration. GO enrichment analysis, KEGG analysis, Reactome analysis, ConsensusPathDB, and GeneMANIA were used to visualize the functional enrichment of MPC1 and signaling pathways related to MPC1. The correlation analysis was carried out to examine the relationship between MPC1 and Ferroptosis gene in TIMER 2.0, ncFO, GEPIA Database and Kaplan–Meier Plotter. Results We demonstrated that the expression levels of MPC1 in cervical cancer tissues were lower than those in normal cervical tissues. Kaplan–Meier survival curves showed shorter overall survival in cervical cancer patients with low levels of MPC1 expression. The expression of MPC1 was related to the infiltrating levels of tumor-infiltrating immune cells in cervical cancer. Moreover, MPC1 expression was associated with the iron-mediated cell death pathway, and several important ferroptosis genes were upregulated in cervical cancer cells. Furthermore, after knocking down MPC1 in HeLa cells, the expression of these genes decreased. Conclusion These findings indicate that MPC1 functions as a prognostic indicator and plays a role in the regulation of the ferroptosis pathway in cervical cancer.

Background: Radical hysterectomy (RH) is commonly used to treat early-stage cervical cancer in women of childbearing age and sexual dysfunction due to postoperative vaginal shortening is a major concern. The impact of intraoperative vaginoplasty on prognosis and quality of sexual life in patients with early-stage cervical cancer remains controversial and lacks high-level evidence. However, there are few reports on vaginoplasty after RH to lengthen vagina in patients. This prospective, multi-center, randomized controlled trial aims to explore the impact of peritoneal vaginoplasty with or without ovarian transposition after laparoscopic RH on sexual dysfunction in patients with early-stage cervical cancer. Methods: Eligible patients will be randomly assigned (1:1) to receive peritoneal vaginoplasty or not. The primary evaluation indicators are female sexual function index (FSFI) and male sexual satisfaction scale. The secondary evaluation indicators include EORTC QLQ-CX24, 2-year overall survival (OS), 5-year OS, 2-year progression-free survival (PFS), 5-year PFS and surgery-related complications. The trial will enroll 368 patients from 6 hospitals in China over a 3-year period and follow up for 5 years. Trial registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000040610.

Introduction: Smoking has been proven to increase the risk of cervical cancer, but it is still controversial whether smoking reduces women's ability to clear human papillomavirus (HPV) infection. This study investigated the association between smoking behaviors during follow-up and clearance of HPV infection in women with HPV-positive and pathologically normal uterine cervix in China, using a propensity score matching (PSM) analysis. Methods: The present prospective study included data from women examined in the Gynecology Department of Shanghai General Hospital from January 2018 to June 2020. Twenty patients who smoked throughout follow-up were selected and matched with 60 patients using the 1:3 PSM method on age, marital status, and whether infected with high-risk HPV (HR-HPV). At each visit, smoking and sexual behaviors were collected. The Kaplan-Meier method and a Cox proportional hazard regression model were used to evaluate the probability of clearing HPV infection within a 2-year follow-up. Results: A total of 80 patients were included in the study, all of whom were infected with at least one HR-HPV type at baseline. Current smokers had a lower likelihood of clearing the HPV infection than current non-smokers, after adjusting for a history of sexually transmitted diseases (STD), HPV infection status, and sexual behaviors during follow-up (AHR=0.478; 95% CI: 0.239-0.958, p=0.037). Additionally, longer duration, higher frequency and larger doses of smoking correlated with the lower clearance possibility of HPV infection (p for trend=0.029, 0.022 and 0.026, respectively). Conclusions: This study showed that the use of tobacco throughout follow-up could increase the risk of a persistent HPV infection, this risk being higher for smokers with heavier tobacco consumption. Our results should alert HPV-positive women to reiterate the advice to cut-back on or stop smoking.

Background Although global contraceptive coverage has increased significantly, high rates of unintended pregnancy remain the current global status quo. A comparative analysis of the differences and correlations of knowledge, attitude and practice (KAP) of sexual and reproductive health (SRH) of both partners will help guide public health work according to gender characteristics and needs, and reduce the occurrence of unintended pregnancy. Methods A questionnaire survey of people with unintended pregnancies including women and their male partners (n = 1,275 pairs) who sought help from the Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October 2017 to October 2021. Data were collected on sexual and reproductive health knowledge, attitudes, and practices in both partners who had unintended pregnancies. Chi-square test and Logistic regression were used to analyze the relationship between the occurrence of unintended pregnancy and KAP and its influencing factors. Paired odds ratio and McNemar's test were used to estimate the difference and concordance of KAP between partners. Results This study included 1,275 partners with a mean age of 30.0 years. The partner's overall level of KAP is good. Compared with women, men had better knowledge (χ² = 3.93, p = 0.047) and more active contraceptive practices (χ² = 19.44, p < 0.001). In the analysis of partner concordance, male contraceptive intention was found to be better than female [matched pairs odds ratio (ORMP) = 2.56, p < 0.001], and the concordance of positive contraceptive practice between partners increased with male education [adjusted odds ratio (aOR) = 1.556, 95% confidence interval (CI) = 1.185–2.044, p = 0.001]. In partner-paired regression analysis, compared with good contraceptive knowledge in both men and women in the partner, the risk of negative contraceptive practice was 1.7 times (aOR = 1.721, 95% CI = 1.234–2.400, p = 0.001) higher with good contraceptive knowledge in women but negative in men, while women with poor contraceptive knowledge but men with good knowledge are 1.3 times (aOR = 1.349, 95% CI = 1.000–1.819, p = 0.05) more likely to have negative contraceptive practices. In addition, compared with partners with positive contraceptive attitudes, women with positive attitudes but negative men and women with negative attitudes but positive men had 1.7 and 1.4 times the risk of negative contraceptive practices, respectively. Conclusion The study found that unintended pregnancy occurs mainly in young people, and the younger age of first sexual intercourse, the low education background and the lack of discussion of contraception between partners are risk factors for not taking contraceptive measures. Men's better knowledge and contraceptive practices compared with female partners, and poor male contraceptive knowledge and attitudes may lead to a higher risk of negative contraceptive practices, the results suggest that male KAP plays an important role in promoting contraceptive use and reducing unintended pregnancy.

Abstract Background Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. Methods This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. Results For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p

Background Circular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervical cancer are still unclear. Methods CircRNAs related to cervical cancer were screened through the Gene Expression Omnibus (GEO) database. qRT-PCR was used to verify the expression of circ_0087429 in cervical cancer tissues and cells. Then, in vivo and in vitro experiments were conducted to evaluate the role of circ_0087429 in the progression of cervical cancer. The role of the circ_0087429/miR-5003-3p/osteoglycin (OGN) axis in the epithelial to mesenchymal transition (EMT) was confirmed by rescue experiments, fluorescence in situ hybridization, luciferase reporter assays, immunofluorescence staining and western blotting. The inhibitory effect of Eukaryotic initiation factor 4A-III (EIF4A3) on the biogenesis of circ_0087429 was verified by RNA immunoprecipitation (RIP) assays and qRT-PCR. Results circ_0087429 is significantly downregulated in cervical cancer tissues and cells and negatively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging and lymphatic metastasis in cervical cancer patients. circ_0087429 can significantly inhibit the proliferation, migration, invasion and angiogenesis of cervical cancer in vitro and tumour growth and metastasis in vivo. OGN is significantly downregulated in cervical cancer tissues and cells. circ_0087429 can upregulate the expression of OGN by competitively binding with miR-5003-3p, thereby reversing EMT and inhibiting the progression of cervical cancer. EIF4A3 can inhibit circ_0087429 expression by binding to its flanking regions. Conclusions As a tumour suppressor, circ_0087429 regulated by EIF4A3 can reverse EMT and inhibit the progression of cervical cancer through the miR-5003-3p/OGN axis. It is expected to become a potential target for the treatment of cervical cancer.

Objective Recent molecular profiling revealed that cancer-associated fibroblasts (CAFs) are essential for matrix remodeling and tumor progression. Our study aimed to investigate the role of flavin-containing monooxygenase 2 (FMO2) in epithelial ovarian cancer (EOC) as a novel CAF-derived prognostic biomarker. Methods Primary fibroblasts were isolated from EOC samples. Microdissection and single-cell RNA sequencing (scRNA-seq) datasets (including TCGA, GSE9891, GSE63885, GSE118828 and GSE178913) were retrieved to determine the expression profiles. Gene set enrichment analysis (GSEA) was used to explore the correlation between FMO2 and stromal activation as well as immune infiltration. The predictive value of FMO2 and combined macrophage infiltration level was verified in an independent EOC cohort (n = 113). Results We demonstrated that FMO2 was upregulated in tumor stroma and correlated with fibroblast activation. Besides, FMO2 had the predictive power for worse clinical outcome of EOC patients. In the mesenchymal subtype of EOC, the FMO2-defined signature revealed that FMO2 contributed to infiltration of tumor-infiltrating lymphocytes. Moreover, we confirmed the positive correlation between FMO2 and CD163⁺ cell infiltration level in EOC tissues, and showed that combination of FMO2 expression with CD163⁺ cell infiltration level in the tumor stroma could predict poor overall survival (HR = 3.63, 95% CI = 1.93–6.84, p = 0.0008). Additionally, FMO2 also predicted the prognosis of patients with ovarian cancer based on the expression of immune checkpoints (such as PD-L1 and PD1). Conclusion Our results address the tumor-supporting role of FMO2 in EOC and its association with immune components, and it might be a prospective target for stroma-oriented therapies against EOC.

Progestin resistance is the main obstacle for the conservative therapy to maintain fertility in women with endometrial cancer. Brusatol was identified as an inhibitor of the NRF2 pathway; however, its impact on progestin resistance and the underlying mechanism remains unclear. Here, we found that brusatol sensitized endometrial cancer to progestin by suppressing NRF2-TET1-AKR1C1-mediated progestin metabolism. Brusatol transcriptionally suppressed AKR1C1 via modifying the hydroxymethylation status in its promoter region through TET1 inhibition. Suppression of AKR1C1 by brusatol resulted in decreased progesterone catabolism and maintained potent progesterone to inhibit endometrial cancer growth. This inhibition pattern has also been found in the established xenograft mouse and organoid models. Aberrant overexpression of AKR1C1 was found in paired endometrial hyperplasia and cancer samples from the same individuals with progestin resistance, whereas attenuated or loss of AKR1C1 was observed in post-treatment samples with well progestin response as compared with paired pre-treatment tissues. Our findings suggest that AKR1C1 expression pattern may serve as an important biomarker of progestin resistance in endometrial cancer. For precancerous/endometrial cancer patients with fertility maintain desire, progestin resistance is the main obstacle of conservative therapy. The authors found that brusatol, as a natural compound, suppresses progestin metabolism through regulating the NRF2-TET1-AKR1C1 pathway to sensitize precancerous/endometrial cancers to progestin and relieve progestin resistance. This study indicates that progestin combined with brusatol may enhance the treatment effects and that AKR1C1 expression patterns may serve as an important biomarker of progestin resistance in endometrial cancer.