Jing Yang

Decoding UTROSCT heterogeneity: systematic clinicopathological evaluation combined with molecular profiling

Abstract Uterine tumor resembling ovarian sex cord tumor (UTROSCT) constitutes an exceptionally rare histological subset of uterine mesenchymal neoplasms. While most cases have benign clinical behavior, a subset of UTROSCTs exhibits clinically aggressive behavior characterized by recurrence and metastasis. Here, we present a cohort of 25 UTROSCT cases molecularly confirmed by recurrent fusion gene detection, including ESR1::NCOA3 ( n  = 12), GREB1::NCOA1 ( n  = 6), ESR1::NCOA2 ( n  = 3), GREB1::NCOA2 ( n  = 2), GREB1::SS18 ( n  = 1), and GREB1::CTNNB1 ( n  = 1). Notably, six cases (6/25, 24%) demonstrated recurrence/metastasis: two cases showed intrauterine recurrence (harboring ESR1::NCOA3 and GREB1::NCOA1 fusions), while four developed extrauterine metastases (carrying ESR1::NCOA3 , ESR1::NCOA2, GREB1::NCOA1, and GREB1::NCOA2 fusions), with one fatality. To dissect the biological basis of UTROSCT aggressiveness, we performed integrated clinicopathologic, immunohistochemical, and molecular profiling. Multivariate analysis identified tumor size >5 cm, FIGO stage IB, and lymphovascular space invasion (LVSI) as independent predictors of recurrence/metastasis, whereas histologic features, proliferation index, and fusion gene subtypes lacked prognostic significance. Multi‐omics analysis of primary versus metastatic tumors revealed striking copy number variations (CNVs) exclusively in metastatic lesions. Specifically, heterozygous losses of SMARCB1 (2/4 metastatic cases) and ATRX (1/4 metastatic cases) were identified; both play critical roles in chromatin remodeling. These genetic alterations were conspicuously absent in primary tumors, suggesting their potential role in metastatic progression. Our findings represent the first demonstration of CNV‐driven oncogenic evolution in UTROSCTs, particularly implicating SWI/SNF complex dysregulation in metastatic competence.

Identifying risk factors for cancer-specific early death in patients with advanced endometrial cancer: A preliminary predictive model based on SEER data

Objective To identify risk factors associated with cancer-specific early death in patients with advanced endometrial cancer and to develop a preliminary nomogram prediction model based on these factors, with an emphasis on the potential implications for clinical practice. Methods Patients from the Surveillance, Epidemiology, and End Results (SEER) database in the United States from 2018 to 2021 were included in the study. The study data was randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Multivariate logistic regression analysis was performed in the training cohort to screen for risk factors for cancer-specific early mortality in advanced endometrial cancer patients, and a preliminary nomogram prediction model was further constructed. The results of the Receiver Operating Characteristic (ROC) curve, calibration analysis, and clinical decision curve analysis (DCA) were presented for transparency. Results Significant risk factors for cancer-specific early death were identified, including tumor size (≥101 mm, OR = 2.11, P < 0.001), non-endometrioid histology (OR = 3.11, P < 0.001), high tumor grade (G3, OR = 2.68, P = 0.007), advanced tumor stages (T3-T4, OR = 1.84, P = 0.004), and metastatic stage (M1, OR = 2.05, P < 0.001), as well as the presence of liver metastases (OR = 2.21, P = 0.005) and brain metastases (OR = 8.08, P < 0.001). Protective factors that were significantly associated with a reduced risk of early death included hysterectomy (OR = 0.13, P = 0.012), radical surgery (OR = 0.21, P < 0.001), radiation therapy (OR = 0.40, P < 0.001), and chemotherapy (OR = 0.31, P < 0.001). A preliminary nomogram model was demonstrated adequate predictive performance with AUC values of 0.89 (95% CI 0.87 to 0.91) in the training cohort and 0.88 (95% CI 0.84 to 0.91) in the validation cohort. The model’s predictive performance was further supported by the calibration and DCA analyses, suggesting its potential clinical utility. Conclusion This study identified key risk factors for early cancer-specific mortality in patients with advanced endometrial cancer. The preliminary nomogram model holds promise for predicting early death risk and could be valuable in clinical practice. Future work may explore its performance with additional data to ensure broad applicability.

Integrated morphological, immunohistochemical, and genomic profiling identifies uterine leiomyoma patients with hereditary leiomyomatosis and renal cell cancer syndrome: a comprehensive analysis of 252 cases

Abstract Fumarate hydratase‐deficient uterine leiomyomas (FHd‐ULMs) represent a molecularly distinct subgroup of smooth muscle tumours associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. This study determined the detection rate of germline pathogenic FH variants in FHd‐ULMs using paired tumour‐normal sequencing and assessed the utility of integrated morphological, immunohistochemical (FH/2SC), genomic, and clinical features for selecting cases suspected of HLRCC. Histopathological assessment of the 252 FHd‐ULMs revealed consistent morphological features, whereas molecular profiling identified three biologically distinct categories. Germline FH ‐mutated (hereditary) cases constituted 35.7% (74/207) of this FHd‐ULM cohort, four of which showed concomitant somatic copy‐number alterations. This contrasted with the somatic‐mutated subgroup, which comprised 50.7% (105/207), including 18.4% (38/207) with isolated somatic copy‐number losses. The remaining 13.6% (28/207), though lacking detectable FH mutations, were classified with somatic‐mutated cases as sporadic FHd‐ULMs based on shared clinicopathological features. Molecular analysis identified shared variant distributions across exons 2–10, with exons 5 and 7 in the fumarate lyase domain emerging as the predominant mutational hotspots. Notably, truncating mutations showed significantly higher prevalence in hereditary cases versus somatic variants ( p  < 0.01). Clinically, hereditary FHd‐ULMs presented at younger ages (< 45 years) and manifested more aggressive phenotypes, including elevated rates of infertility (54.1% versus 26.4%), multifocal tumour development (86.5% versus 53.4%), increased surgical interventions (44.6% versus 11.5%), and familial leiomyoma clustering (51.4% versus 24.2%). Our results identify germline FH mutations, which confer significant HLRCC risk, in 35.7% of FHd‐ULMs, while somatic alterations account for the majority of cases. To ensure efficient resource allocation, we propose a stratified diagnostic approach: initial universal FH/2SC immunohistochemical screening for ULMs displaying ≥ 3 FH‐deficient morphological features, followed by confirmatory genetic testing in high‐risk individuals, defined by either aberrant FH/2SC immunoreactivity or, in immunohistochemically normal cases, age < 45 years together with a personal/family history of multiple symptomatic leiomyomas or HLRCC‐associated neoplasms. © 2026 The Pathological Society of Great Britain and Ireland.

Multi-Task Collaborative Assisted Training Method for Grouping Fuzzy Categories Classification of Cervical Cancer Cells

Cervical cancer is a malignant tumor that endangers women's life and health. While deep learning has enhanced the accuracy of cervical cell classification, there remain obstacles impeding further performance enhancement, including the similarities between different categories, variability between single cells and cell clusters, as well as the accuracy of annotations. To address these issues, a novel multi-task collaborative framework for cervical cell classification is proposed. Specifically, to solve the similarity between different categories, we propose a grouping cell contrast auxiliary branch, which divides cervical cells into different groups and utilizes supervised contrastive learning to learn representative feature between different categories. And we introduce a multi-level cell classification auxiliary branch that simultaneously performs 5-class, 3-class, and 2-class classification tasks, and explicitly constrains the inter-class relationship learning of cervical cells. Furthermore, to solve the variations within the same category of single cells and cell clusters, we propose an image reconstruction auxiliary branch, which encourages the model to learn more contextual features. Finally, to solve subjectivity and accuracy of annotations, we introduce a soft label distillation auxiliary branch, which constrains the consistency of probability distributions between the encoder and the momentum encoder. It is worth noting that these auxiliary branches only work during training and will not add additional computational consumption during inference. We validate on the HSJCC, DSCC and SIPaKMeD datasets. Compared to existing methods, our approach has achieved outstanding performance and effectively mitigates the issues raised, demonstrating its effectiveness in automated cervical cell classification.

Advanced Glycation End Products as a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study

Ovarian cancer is the sixth leading cause of cancer-related death in women, and both occurrence and mortality are increased in women over the age of 60. There are documented age-related changes in the ovarian cancer microenvironment that have been shown to create a permissive metastatic niche, including the formation of advanced glycation end products, or AGEs, that form crosslinks between collagen molecules. Small molecules that disrupt AGEs, known as AGE breakers, have been examined in other diseases, but their efficacy in ovarian cancer has not been evaluated. The goal of this pilot study is to target age-related changes in the tumor microenvironment with the long-term aim of improving response to therapy in older patients. Here, we show that AGE breakers have the potential to change the omental collagen structure and modulate the peritoneal immune landscape, suggesting a potential use for AGE breakers in the treatment of ovarian cancer.

Interleukin‐6 and Hypoxia Synergistically Promote EMT‐Mediated Invasion in Epithelial Ovarian Cancer via the IL‐6/STAT3/HIF‐1α Feedback Loop

Extensive peritoneal spread and capacity for distant metastasis account for the majority of mortality from epithelial ovarian cancer (EOC). Accumulating evidence shows that interleukin‐6 (IL‐6) promotes tumor invasion and migration in EOC, although the molecular mechanisms remain to be fully elucidated. Meanwhile, the hypoxic microenvironment has been recognized to cause metastasis by triggering epithelial–mesenchymal transition (EMT) in several types of cancers. Here, we studied the synergy between IL‐6 and hypoxia in inducing EMT in two EOC cell lines, A2780 cells and SKOV3 cells. Exogenous recombination of IL‐6 and autocrine production of IL‐6 regulated by plasmids both induced EMT phenotype in EOC cells characterized by downregulated E‐cadherin as well as upregulated expression of vimentin and EMT‐related transcription factors. The combined effects of IL‐6 and hypoxia were more significant than those of either one treatment on EMT. Suppression of hypoxia‐inducible factor‐1α (HIF‐1α) before IL‐6 treatment inhibited the EMT phenotype and invasion ability of EOC cells, indicating that HIF‐1α occupies a key position in the regulatory pathway of EMT associated with IL‐6. EMT score was found positively correlated with mRNA levels of IL‐6, signal transducer and activator of transcription 3 (STAT3), and HIF‐1α, respectively, in 489 ovarian samples from The Cancer Genome Atlas dataset. Next, blockade of the abovementioned molecules by chemical inhibitors reversed the alteration in the protein levels of EMT markers induced by either exogenous or endogenous IL‐6. These findings indicate a positive feedback loop between IL‐6 and HIF‐1α, and induce and maintain EMT phenotype through STAT3 signaling, which might provide a novel rationale for prognostic prediction and therapeutic targets in EOC.

CircPSMC3 alleviates the symptoms of PCOS by sponging miR‐296‐3p and regulating PTEN expression

AbstractPolycystic ovary syndrome (PCOS), the most common female endocrine disease that causes anovulatory infertility, still lacks promising strategy for the accurate diagnosis and effective therapeutics of PCOS attributed to its unclear aetiology. In this study, we determined the abnormal reduction in circPSMC3 expression by comparing the ovarian tissue samples of PCOS patients and normal individuals. The symptom relief caused by up‐regulation of circPSMC3 in PCOS model mice suggested the potential for further study. In vitro functional experiments confirmed that circPSMC3 can inhibit cell proliferation and promote apoptosis by blocking the cell cycle in human‐like granular tumour cell lines. Mechanism study revealed that circPSMC3 may play its role through sponging miR‐296‐3p to regulate PTEN expression. Collectively, we preliminarily characterized the role and possible insights of circPSMC3/miR‐296‐3p/PTEN axis in the proliferation and apoptosis of KGN cells. We hope that this work provides some original and valuable information for the research of circRNAs in PCOS, not only to better understand the pathogenesis but also to help provide new clues for seeking for the future therapeutic target of PCOS.

Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment

Mesothelin (MSLN), a glycoprotein normally expressed by mesothelial cells, is overexpressed in ovarian cancer (OvCa) suggesting a role in tumor progression, although the biological function is not fully understood. OvCa has a high mortality rate due to diagnosis at advanced stage disease with intraperitoneal metastasis. Tumor cells detach from the primary tumor as single cells or multicellular aggregates (MCAs) and attach to the mesothelium of organs within the peritoneal cavity producing widely disseminated secondary lesions. To investigate the role of host MSLN in the peritoneal cavity we used a mouse model with a null mutation in the MSLN gene (MSLNKO). The deletion of host MSLN expression modified the peritoneal ultrastructure resulting in abnormal mesothelial cell surface architecture and altered omental collagen fibril organization. Co-culture of murine OvCa cells with primary mesothelial cells regardless of MSLN expression formed compact MCAs. However, co-culture with MSLNKO mesothelial cells resulted in smaller MCAs. An allograft tumor study, using wild-type mice (MSLNWT) or MSLNKO mice injected intraperitoneally with murine OvCa cells demonstrated a significant decrease in peritoneal metastatic tumor burden in MSLNKO mice compared to MSLNWT mice. Together, these data support a role for host MSLN in the progression of OvCa metastasis.

Long Noncoding RNA LINC01554 as a Novel Biomarker for Diagnosis and Prognosis Prediction of Epithelial Ovarian Cancer

Objective. This study was aimed at exploring the diagnostic and prognostic value of long noncoding RNA LINC01554 (LINC01554) in epithelial ovarian cancer (EOC) patients. Patients and Methods. The expressions of LINC01554 in 161 EOC patients were analyzed using RT-PCR. The area under the ROC curve (AUC) was used to estimate the effectiveness of LINC01554 for prediction. The chi-square test was performed to explore the association between LINC01554 expressions and clinical characteristics in EOC patients. Kaplan-Meier assays were conducted for the examination of the influence of LINC01554 expression on the overall survival of EOC patients. Multivariate analyses were carried out to further determine prognostic values of LINC01554 expression in EOC patients. Results. LINC01554 expressions were strongly downregulated in EOC specimens compared with matched nontumor specimens ( p < 0.01 ). Importantly, LINC01554 provided a high diagnostic performance for the detection of EOC specimens ( AUC = 0.7827 ; p < 0.001 ). Low expression of LINC01554 was distinctly associated with the FIGO stage ( p = 0.034 ) and distant metastasis ( p = 0.007 ). The assays of survival data (five years) revealed that the 5-year overall survival of the low LINC01554 expression group was distinctly shorter than that of the high LINC01554 expression group ( p = 0.0017 ). Finally, in the multivariate Cox model, LINC01554 expression ( RR = 2.863 , 95% CI: 1.185-4.421, p = 0.014 ) was demonstrated to be an independent prognostic factor for overall survival of EOC patients. Conclusions. Our findings suggested that LINC01554 is an important EOC-related lncRNA, providing a potential diagnostic, prognostic biomarker and therapeutic target for EOC patients.

Prevalence, genotype distribution and risk factors of cervical HPV infection in Yangqu, China: a population-based survey of 10086 women

Human papillomavirus(HPV) infection is a necessary factor for the development of cervical cancer. The HPV vaccine is currently available, but there is still a lack of large-scale research on the distribution and risk factors of HPV. The aim of this study is to investigate the genotype distribution and risk factors of HPV infection in Yangqu which is located in North China. This study enrolled 10086 women aged <65 years from Yangqu County. HPV genotypes were identified via standard HPV DNA testing. The overall prevalence of HPV infection was 8.92%. The prevalence of high-risk HPV types was 8.80%, and it was 0.38% for low-risk HPV types. Single genotype infection accounted for 67.91% in HPV-positive cases. The most common HPV genotypes were HPV-16, -52, and -58. HPV-18 was only the 11th most common type in HPV-positive cases. Women ≥50 years of age had the highest prevalence rate of HPV, and women <30 years had the lowest prevalence rate. The distribution of HPV genotypes also varied among the three age groups: <30, 30-49, and ≥50 years. The risk factors that contributed to the rate of HPV infection included low educational level, low income, smoking, age at first sexual encounter <23 years old, and number of births ≥3 times. This large routine clinical practice report of HPV prevalence and genotype distribution revealed the characteristics of HPV infection-type distributions in Shanxi Province, which should be considered in formulating comprehensive prevention strategies including vaccination for cervical cancer in China.

Effect of a new nursing organization management mode constructed by appreciative inquiry on gynecological tumor patients in the perioperative period

ABSTRACT Objective: To evaluate the effect of a new nursing organizational management model based on appreciative inquiry on gynecological tumor patients during the perioperative period. Method: A retrospective analysis was conducted on 204 gynecological tumor patients who underwent surgical treatment between June 2021 and June 2024. Patients were assigned to a control group (n = 102; routine nursing organization management mode) or a study group (n = 102; new nursing organization management mode constructed by appreciative inquiry) according to their nursing mode during the perioperative period. Results: Both groups had increased World Health Organization Quality of Life Scale Brief Version (WHOQOL-BREF) scores and decreased Pelvic Floor Distress Inventory-Short Form 20 (PFDI-20) scores compared to before the intervention. The study group had higher WHOQOL-BREF scores and lower PFDI-20 scores than the control group (p &lt; 0.05). Scores on the Social Impact Scale in each dimension and the total score declined in both groups compared to baseline, with lower scores observed in the study group than in the control group (p &lt; 0.05). Conclusion: The new nursing organizational management model developed using appreciative inquiry can optimize perioperative indicators, improve pelvic floor dysfunction, and enhance psychological resilience.