Yu Zhang

A Macrophage-Driven Multimodal Nanoplatform Conquers Ovarian Cancer Peritoneal Metastasis

Ovarian cancer peritoneal metastasis remains a lethal clinical challenge, with hyperthermic intraperitoneal chemotherapy (HIPEC) offering limited survival benefits due to off-target toxicity, position-dependent delivery, and the lack of durable immune activation. Herein, we report a macrophage-driven precision nanoplatform that enables tumor-homing delivery and multimodal therapeutic synergy. By engineering M1-polarized, tumor-tropic macrophages to deliver mitoxantrone (MTO)-loaded metal-organic framework nanoparticles (MTO NPs@M1), we achieve selective accumulation at peritoneal metastases via the innate homing capacity of macrophages. Upon near-infrared (NIR) irradiation, the system triggers on-demand release of MTO NPs, enabling a trimodal therapeutic strategy: (I) chemotherapy via MTO-induced DNA damage, (II) photothermal ablation, and (III) chemodynamic therapy (CDT) through Cu-MOF-mediated •OH generation. This combined strategy induces strong immunogenic cell death (ICD), promoting dendritic cell maturation and cytotoxic T cell infiltration. Combined with anti-PD-L1 checkpoint blockade, the platform achieves near-complete eradication of peritoneal metastases in murine ovarian cancer and elicits robust adaptive immune memory that prevents recurrence, as confirmed in a tumor rechallenge model. By integrating targeted delivery, multimodal tumor eradication, and immune activation, this strategy addresses the limitations of conventional HIPEC and provides a promising translational approach for ovarian cancer peritoneal metastasis.

[Retracted] Relationship between Prognosis, Immune Infiltration Level, and Differential Expression of PARVG Gene in Uterine Corpus Endometrial Carcinoma

Endometrial cancer (UCEC) is very common in gynecological diseases and ranks second in the death cause of gynecological cancer in developed countries. The connection between the overall survival of UCEC patients and immune invasion of the tumor microenvironment is positive. The PARVG gene has not been given notice in cancer, and its mechanism is unknown. The research utilized TCGA data to test the function of PARVG in UCEC. The manifestation of PARVG in UCEC was studied by GEPIA. By assessing the survival module, the authors learned the impact of PARVG on the survival of people with UCEC and then obtained UCEC information from TCGA. This study uses logistic regression to prove the possible relationship between PARVG expression and clinical information. From the research of Cox regression, clinicopathological characteristics of people with TCGA were connected with overall survival. Furthermore, the “correlation” module of GEPIA and CIBERSORT was used to study the association between cancer immune invasion and PARVG . Using univariate logistic regression analysis with PARVG expression as a categorical variable (median expression value of 2.5), the result suggested that raised PARVG expression was considerably connected with tumor status, pathological stage, and lymph nodes. Multiple factor studies have shown that upregulation of PARVG, distant metastasis, and negative pathological stage are absolute elements of excellent prognosis. In addition, CIBERSORT analysis was utilized to determine that raised PARVG expression has a positive connection with immune infiltration by T cells, mast cells, neutrophils, and B cells. This is recognized in GEPIA’s “correlation” module. The above outcomes show us that the raised expression of PARVG is associated with a good prognosis and it raises the proportion of immune cells (such as T cells, mast cells, neutrophils, and B cells) in UCEC. These outcomes tell us that PARVG can be utilized as a possible biomarker to evaluate UCEC’s immune infiltration levels and prognosis.

Identification of the 11-lncRNA signatures associated with the prognosis of endometrial carcinoma

Endometrial carcinoma (EC) is the fourth most common cancer in women. Some long non-coding RNAs (lncRNAs) are regarded as potential prognostic biomarkers or targets for treatment of many types of cancers. We aim to screen prognostic-related lncRNAs and build a possible lncRNA signature which can effectively predict the survival of patients with EC. We obtained lncRNA expression profiling from the TCGA database. The patients were classified into training set and verification set. By performing Univariate Cox regression model, Robust likelihood-based survival analysis, and Cox proportional hazards model, we developed a risk score with the Cox co-efficient of individual lncRNAs in the training set. The optimum cut-off point was selected by ROC analysis. Patients were effectively divided into high-risk group and low-risk group according to the risk score. The OS of the low-risk patients was significantly prolonged compared with that of the high-risk group. At last, we validated this 11-lncRNA signature in the verification set and the complete set. We identified an 11-lncRNA expression signature with high stability and feasibility, which can predict the survival of patients with EC. These findings provide new potential biomarkers to improve the accuracy of prognosis prediction of EC.

An aptamer integrated electrochemistry and photoluminescence dual-mode microfluidic biosensor for sensitive and accurate ovarian cancer extracellular vesicles detection

Extracellular vesicles (EVs) serve as crucial biomarkers for cancer screening due to their close association with the physiological and pathological states of cancer cells. These membrane-bound vesicles carry molecular cargo that reflects the characteristics of their parent cells, making them valuable diagnostic indicators. Current EVs detection methods face significant limitations in clinical applications, particularly regarding sensitivity and accuracy requirements for reliable cancer diagnostics. The critical challenge is to develop sensitive and accurate EVs detection methods for clinical cancer screening. We developed an aptamer-integrated dual-mode microfluidic biosensor combining electrochemistry (EC) and photoluminescence (PL) detection for ovarian cancer EVs screening. The platform utilized aptamer-functionalized gold nanoflowers (Au NFs) integrated with 3D laser-induced graphene (LIG) electrode arrays, achieving a 1.44-fold increase in electroactive surface area. Poly-lysine (PLL) served as the PL detection substrate for capturing fluorescent complexes, enabling simultaneous dual-signal generation. Under optimized conditions, the biosensor achieved a detection range of 10-10 This work presents the first aptamer-integrated EC-PL dual-mode microfluidic biosensor for EVs detection, enabling real-time signal cross-validation and enhanced reliability. The novel combination of Au NFs-3D LIG architecture with PLL-mediated detection strategy significantly improves sensitivity and clinical applicability for point-of-care cancer screening.

Influence of Pre‐Vaccination HPV Status on Vaccine Effectiveness Among Chinese Women: A Multicenter Cross‐Sectional Study

ABSTRACTBackground and AimsHuman papillomavirus (HPV) vaccines have been available in China for only 8 years, and routine HPV testing is not recommended prior to vaccination. Therefore, evaluation of HPV vaccine effectiveness and the impact of pre‐vaccination HPV infection status on vaccine protective effect in Chinese women is warranted.MethodsFrom June 2022 to June 2023, women aged 18 to 50 years without a history of cervical or uterine excision were recruited from three medical institutions. Baseline characteristics were compared between vaccinated and unvaccinated participants, with inverse probability treatment weighting (IPTW) applied to adjust for confounding factors. HPV infection rates and vaccine effectiveness (VE) were calculated. Additionally, a sub‐group analysis was conducted among vaccinated women to explore the impact of pre‐vaccination HPV infection status.ResultsAfter adjusting for group differences, the vaccine effectiveness against new HPV16/18 infections was 76.1% (95% CI: 58.7%–86.2%) among 2285 participants. Older age and possession of a master's degree or higher were identified as protective factors, whereas increased parity and exclusive use of oral contraceptives were determined to be risk factors for HPV16/18 infection. Women with unknown pre‐vaccination HPV status exhibited significantly higher post‐vaccination rates of high‐risk HPV infections (RR 4.278, 95% CI: 2.537–7.215) compared to those who were HPV‐negative prior to vaccination. However, no significant difference in new high‐risk HPV infection rates was observed between pre‐vaccination HPV‐negative and HPV‐positive women.ConclusionIn addition to HPV vaccination, factors such as age, parity, exclusive use of oral contraceptives, and higher education attainment were independently associated with HPV16/18 infection rates. Pre‐vaccination HPV infection status did not significantly influence the protective efficacy of the HPV vaccine against previously unencountered HPV types.

Optimizing the Follow‐Up Interval After Successful Cold Knife Conization of CIN3: A 10‐Year Retrospective Cohort Study

ABSTRACTBackgroundThis study was conducted to identify the risk of residual or recurrent high‐grade squamous intraepithelial lesions or worse (HSIL+) in patients with successful conization and to develop a customized management strategy.MethodsThis retrospective study included 939 patients who underwent cold knife conization (CKC) for cervical intraepithelial neoplasia 3 at a hospital in China between January 1, 2013 and December 31, 2020. Demographic characteristics and test results were obtained before and 6, 12, and 24 months after CKC and annually thereafter. Human papillomavirus (HPV) persistence was defined as HPV positive at both 6 and 12 months after CKC, and the primary endpoint was residual or recurrent HSIL+ after CKC.ResultsThe mean follow‐up period was 68.8 months. In total, 61 (6.5%) patients had HPV persistence, and 19 (2.0%) had residual or recurrent HSIL+. The risk of residual or recurrent HSIL+ was increased in patients with HPV infection at 6 months (hazard ratio [HR], 84.6; 95% confidence interval [CI], 11.2–641) and 12 months (HR, 214; 95% CI, 28.1–1625) after CKC, and HPV persistence after CKC (HR, 244; 95% CI, 32.2–1854). Comparing two different colposcopic referral criteria for HPV persistence and HPV positive 6 months post‐CKC, substantially fewer colposcopies were performed per case of residual or recurrent HSIL+ detected in patients with HPV persistence after CKC (3.39 vs. 8.28).ConclusionsThe risk of residual or recurrent HSIL+ was higher in patients with HPV persistence after CKC. In patients with negative margins, extending the follow‐up interval to 12 months may reduce the number of HPV tests and colposcopy referral rates while maintaining HSIL+ detection.

Targeting HPV for the prevention, diagnosis, and treatment of cervical cancer

Abstract Despite advances in screening and prevention, cervical cancer (CC) remains an unresolved public health issue and poses a significant global challenge, particularly for women in low-income regions. Human papillomavirus (HPV) infection, especially with the high-risk strains, is a primary driver of cervical carcinogenesis. Emerging evidence indicates that integrating HPV testing with existing approaches, such as cervical cytology and visual inspection, offers enhanced sensitivity and specificity in CC screening. HPV infection-associated biomarkers, including HPV E6/E7 oncogenes, p16^INK4a, DNA methylation signatures, and non-coding RNAs, offer valuable insights into disease progression and the development of personalized interventions. Preventive and therapeutic vaccination against HPV, along with tertiary prevention strategies such as the use of antiviral and immune-modulating drugs for HPV-related lesions, show great clinical potential. At the mechanistic level, single-cell RNA sequencing analysis and the development of organoid models for HPV infection provide new cellular and molecular insights into HPV-related CC pathogenesis. This review focuses on the crucial roles of HPV in the prevention, diagnosis, and treatment of CC, with particular emphasis on the latest advancements in screening and disease intervention.

Recurrence‐Associated Multi‐RNA Signature to Predict Disease‐Free Survival for Ovarian Cancer Patients

Ovarian cancer (OvCa) is an intractable gynecological malignancy due to the high recurrence rate. Several molecular biomarkers have been previously screened for early identifying patients with a high recurrence risk and poor prognosis. However, all the known studies focused on a single type of RNAs, not integrating various types. This study was to construct a new multi‐RNA‐based model to predict the recurrence and prognosis for OvCa patients by using the messenger RNA (mRNA, including long noncoding RNA (lncRNA)) and microRNA (miRNA) sequencing data of The Cancer Genome Atlas database. After univariate Cox regression and least absolute shrinkage and selection operator analyses, a multi‐RNA‐based signature (2 miRNAs: hsa‐miR‐508, hsa‐miR‐506; 1 lncRNA: TM4SF1‐AS1; 11 mRNAs: MAGI3, SLAMF7, GLI2, PDK1, ARID3A, PLEKHG4B, TNFAIP8L3, C1QTNF3, NDUFAF1, CH25H, TMEM129) was generated and used to establish a risk score model. The high‐ and low‐risk patients classified by the median risk score exhibited significantly different recurrence risks (89% versus 61%, p < 0.001) and survival time (the area under the receiver operating characteristic curve (AUC) = 0.901 for 5‐year disease‐free survival (DFS)). This risk model was independent of other clinical features and superior to pathologic staging for DFS prediction (AUC, 0.906 versus 0.524; C‐index, 0.633 versus 0.510). Furthermore, some new interaction axes were revealed to explain the possible functions of these RNAs (competing endogenous RNA: TM4SF1‐AS1‐miR‐186‐STEAP2, LINC00536‐miR‐508‐STEAP2, LINC00475‐miR‐506‐TMEM129; coexpression: LINC00598‐PLEKHG4B). In conclusion, this multi‐RNA‐based risk model may be clinically useful to stratify OvCa patients with different recurrence risks and survival outcomes and included RNAs may be potential therapeutic targets.

Neoadjuvant Chemotherapy Followed by Radical Surgery versus Radiotherapy (with or without Chemotherapy) in Patients with Stage IB2, IIA, or IIB Cervical Cancer: A Systematic Review and Meta-Analysis

Background. This study was to compare the efficacy and safety between neoadjuvant chemotherapy followed by radical surgery (NACT+RS) and radiotherapy only (RT) or concurrent chemoradiotherapy (CCRT) for treatment of patients with stage IB2, IIA, or IIB cervical cancer. Method. The electronic databases of PubMed, Embase, and the Cochrane Library were searched to screen relevant studies from their inception to October 2018. Clinical data including overall survival (OS), disease-free survival (DFS), and adverse events were extracted. Egger’s test was used to evaluate the publication bias, and sensitivity analysis was conducted to estimate the robustness of results. Results. Finally, three randomized controlled trials (RCTs) and two case-control studies consisting of 1,275 patients with stage IB2, IIA, or IIB cervical cancer were included in the current study. Overall, pooled results showed no significant differences in OS ((hazard ratio HR=0.603, 95%CI=0.350−1.038) and DFS (HR=0.678, 95%CI=0.242−1.904) for patients treated with NACT+RS compared with RT only or CCRT, but the subgroup analysis showed that the OS and DFS were significantly longer in the NACT+RS groups than the RT or CCRT group (OS: HR=0.431, 95%CI=0.238−0.781, p=0.006; DFS: HR=0.300, 95%CI=0.187−0.482, p<0.001) for the population with median follow-up time of more than 60 months. For adverse events, the incidence of thrombocytopenia in the NACT+RS group was significantly higher than that in the RT only or CCRT group (relative risk RR=3.240, 95% CI 1.575-6.662), while the incidence of diarrhea was significantly lower than that in the RT only or CCRT group (RR=0.452, 95% CI =0.230-0.890). Conclusion. These findings suggest that the short-term therapeutic effects of the two treatments may be possibly equal for patients with stage IB2-IIB cervical cancer, but the long-term effects for improving OS and DFS may be better using NACT+RS compared with the RT only or CCRT.

Circ‐DTL sponges miR‐758‐3p to accelerate cervical cancer malignant progression by regulating DCUN1D1 expression

AbstractCircular RNAs (circRNAs) play important roles in regulating various cancer progression. However, the function and clinical significance of circ‐denticleless E3 ubiquitin proteinligase homolog (DTL) in cervical cancer (CC) have not been studied. The present work explored the function and mechanism of circ‐DTL in CC development. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to examine the expression of circ‐DTL, miR‐758‐3p, and DCUN1D1. Cell Counting Kit‐8 (CCK‐8) and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays were used to detect cell proliferation. Cell cycle and cell apoptosis were investigated by flow cytometry. Wound‐healing assay and transwell assay were conducted to assess cell migration and cell invasion. Western blot assay was carried out to determine protein expression. Dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to identify the relationship between miR‐758‐3p and circ‐DTL or DCUN1D1. Xenograft mouse model assay was conducted to explore the role of circ‐DTL in CC progression in vivo. Circ‐DTL and DCUN1D1 expression were upregulated in CC tissues and CC cells, but miR‐758‐3p expression was downregulated. Knockdown of circ‐DTL inhibited CC cell growth, migration, and invasion and promoted cell cycle arrest and cell apoptosis. Circ‐DTL could sponge miR‐758‐3p to modulate CC cell progression. Moreover, miR‐758‐3p inhibited CC malignant development by suppressing DCUN1D1 expression. In addition, circ‐DTL knockdown repressed CC cell tumor properties in vivo. Circ‐DTL acted as a tumor promoter in CC development by regulating the miR‐758‐3p/DCUN1D1 pathway.

Circ_0005615 promotes cervical cancer cell growth and metastasis by modulating the miR‐138‐5p/KDM2A axis

AbstractCervical cancer (CC) is a highly fatal gynecological malignancy due to its high metastasis and recurrence rate. Circular RNA (circRNA) has been regarded as a regulator of CC. However, the underlying molecular mechanism of circ_0005615 in CC remains unclear. The levels of circ_0005615, miR‐138‐5p, and lysine demethylase 2A (KDM2A) were measured using qRT‐PCR or western blot. Cell proliferation was assessed by Cell Counting Kit‐8, 5‐ethynyl‐2′‐deoxyuridine, and colony formation experiments. Cell invasion and migration were tested by transwell assay and wound healing assay. Flow cytometry and Caspase‐Glo 3/7 Assay kit were used to analyze cell apoptosis. The expression of proliferation‐related and apoptosis‐related markers was detected by western blot. The binding relationships among circ_0005615, miR‐138‐5p, and KDM2A were verified by dual‐luciferase reporter assay or RNA immunoprecipitation assay. Xenograft assay was applied to detect the effect of circ_0005615 in vivo. Circ_0005615 and KDM2A were upregulated, while miR‐138‐5p was downregulated in CC tissues and cells. Circ_0005615 knockdown retarded cell proliferation, migration, and invasion, while promoting apoptosis. Besides, circ_0005615 sponged miR‐138‐5p, and miR‐138‐5p could target KDM2A. miR‐138‐5p inhibitor reversed the regulation of circ_0005615 knockdown on CC cell growth and metastasis, and KDM2A overexpression also abolished the inhibitory effect of miR‐138‐5p on CC cell growth and metastasis. In addition, we also discovered that circ_0005615 silencing inhibited CC tumor growth in vivo. Circ_0005615 acted as a tumor promoter in CC by regulating the miR‐138‐5p/KDM2A pathway.

First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial

First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer. ClinicalTrials.gov Identifier: NCT03635489.