Ye Lu

Identification of Five m6A-Related lncRNA Genes as Prognostic Markers for Endometrial Cancer Based on TCGA Database

Background. Due to difficulties involved in its early diagnosis and adequate prognostication, uterine corpus endometrial carcinoma (UCEC) is one of the most serious threats to human health, with the five-year survival rate being as low as roughly 60%. The discovery of specific biomarkers that serve as prognosticators of UCEC is of great significance. The role of N6-methyladenosine- (m6A-) related long noncoding RNAs (lncRNAs) in the pathogenesis of UCEC remains undefined. In this study, we explored the expression profiles of m6A-related lncRNAs of patients with UCEC and identified novel prognostic markers for UCEC. Methods. Gene expression and clinical data were extracted from The Cancer Genome Atlas. Coexpression analysis was performed to identify m6A-related lncRNAs, which were entered into univariate Cox regression models for evaluating the prognosis of UCEC. Clusters of UCEC patients and enrichment pathways were identified using consistent data clustering and gene set enrichment analysis (GSEA). A risk score model was established, and Kaplan–Meier analysis was conducted for investigating overall survival (OS) across two patient groups (high risk and low risk). Lastly, the relationship between the risk score and the cell content of 22 types of immune cells, clusters, age, programmed cell death 1 ligand-1 (PD-L1) expression level, immune score, and pathological grade was analyzed. Results. We identified a total of 2084 lncRNAs associated with m6A, of which 32 lncRNAs were prognostically relevant. Two clusters (clusters 1 and 2) of patients with UCEC were defined; patients in cluster 1 were found to have significantly higher pathological grades and shorter overall survival time compared to those in cluster 2. GSEA showed that “MITOTIC SPINDLE and other pathways” were more enriched in cluster 1. Five major lncRNAs associated with m6A were screened out, and risk score modeling was used for UCEC prognosis prediction. High risk scores were associated with a shorter OS. The risk score was also verified as an independent prognostic indicator for UCEC and was related to immune cell infiltration levels. Finally, we observed a higher pathological grade and greater levels of PD-L1 in the high-risk group than in the low-risk group of patients. Conclusions. m6A-related lncRNAs play an important role in UCEC progression. The risk-based model constructed from the five key m6A-related lncRNAs was implicated in immune cell infiltration and can potentially be an accurate prognosticator for UCEC.

Eliminating VEGFA+ tumor-associated neutrophils by antibody-drug conjugates boosts antitumor immunity and potentiates PD-1 immunotherapy in preclinical models of cervical cancer

Abstract Tumor-associated neutrophils (TANs) actively interact with antibody-drug conjugates (ADCs) within the tumor microenvironment (TME), though the detailed mechanisms governing their response to ADC treatment remain to be fully elucidated. Herein, we explored how ICAM1-targeted ADCs affect TAN dynamics in preclinical models of cervical cancer. We discovered that I-DXd, our in-house ADC targeting cervical cancer, effectively eliminates tumor cells through specific antigen recognition while concurrently depleting pro-tumor VEGFA + TANs via Fcγ receptor-mediated phagocytosis. This dual action promotes an immunologically favorable TME. Through comprehensive preclinical studies, we established a foundational understanding of the synergistic benefits of combining I-DXd treatment with PD-1 immune checkpoint inhibition, thereby opening new avenues for therapeutic intervention in advanced cervical cancer.

Assessment of long‐term sexual function of cervical cancer survivors after treatment: A cross‐sectional study

AbstractObjectivesThis study aimed to investigate the long‐term sexual function of patients with cervical cancer who underwent treatment and to explore influential factors.MethodsThis retrospective cross‐sectional study was conducted at Peking University First Hospital in (Beijing, China). A total of 207 patients, who were diagnosed with Stage IA‐IIA cervical cancer and had undergone surgical treatment (some patients had also been treated with adjuvant radiotherapy and chemotherapy) between January 2010 and August 2020, completed questionnaires via telephone. The median time since diagnosis was 54 (range, 13–138) months. Sexual function was assessed using the validated short form of Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ‐12). The multivariate logistic regression analysis was performed to determine factors influencing sexual function after treatment.ResultsThe mean preoperative PISQ‐12 score was 39.42 ± 3.922, and the mean postoperative PISQ‐12 score was 32.60 ± 6.592, indicating a significant decrease in postoperative PISQ‐12 score compared with preoperation (p < 0.001). In total, 49.8% of the patients had sexual dysfunction after treatment. According to the results of the multivariate logistic regression analysis, longer follow‐up (months), ovariectomy, lack of hormone replacement therapy after ovariectomy and adjuvant radiotherapy were significantly associated with sexual dysfunction after treatment (p < 0.05). There was no significant correlation among surgical method, tumor stage, adjuvant chemotherapy, and sexual dysfunction after treatment.ConclusionsThe sexual function of cervical cancer survivors significantly decreased after treatment, which was related to the length of follow‐up, ovariectomy, and adjuvant radiotherapy. Hormone replacement therapy after ovariectomy can help patients to improve their sexual function.