Exosomes mediate cell-cell crosstalk in cancer progression by transferring their molecular cargos, including long noncoding RNAs (lncRNAs). Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) is a well-known lncRNA associated with cancer angiogenesis and metastasis. However, the presence of MALAT1 in exosomes and the roles and clinical values of exosomal MALAT1 in epithelial ovarian cancer (EOC) remain unknown. The present study focused on the crosstalk between EOC cells and endothelial cells mediated by exosomal MALAT1 and aimed to explore the roles of exosomes and exosomal MALAT1 in EOC angiogenesis and to reveal the clinical relevance and prognostic predictive value of serum exosomal MALAT1 in EOC. We observed that MALAT1 was increased in both metastatic EOC cells and their secreted exosomes. Exosomal MALAT1 derived from EOC cells was transferred to recipient human umbilical vein endothelial cells (HUVECs) via exosomes. In vitro and in vivo experiments demonstrated that MALAT1 knockdown impaired the exosome-mediated proangiogenic activity of HUVECs through certain key angiogenesis-related genes. Clinically, elevated serum exosomal MALAT1 was highly correlated with an advanced and metastatic phenotype of EOC and was an independent predictive factor for EOC overall survival (OS). Moreover, a prognostic nomogram model we constructed showed a good prediction of the probability of 3-year OS of EOC patients according to the c-index (0.751, 95% confidence interval [CI]=0.691-0.811) and calibration curve. Collectively, our data provide a novel mechanism by which EOC cells transfer MALAT1 via exosomes to recipient HUVECs and influence HUVECs by stimulating angiogenesis-related gene expression, eventually promoting angiogenesis. Additionally, circulating exosomal MALAT1 can serve as a promising serum-based, noninvasive predictive biomarker for EOC prognosis.

Natural orifice transluminal endoscopic surgery (NOTES) is a significant innovation in the field of minimally invasive surgery. Transvaginal NOTES has gained the most popularity than other transluminal natural orifices such as mouth, rectum, urinary tract or vagina. Since vNOTES is introduced, many surgeons have developed the technique in various gynecologic surgeries. The aim is to collect the growing evidences of vNOTES in gynecological surgeries and highlight vNOTES with an acceptable safety profile. In the present literature review, the search was carried out using the PubMed database with the following keywords: "natural orifice transluminal endoscopic surgery", "NOTES", "natural orifice" and "gynecologic surgery". The current status of vNOTES in gynecologic surgeries was investigated. A total of 33 studies with 628 cases were included in the review. Our outcomes showed that vNOTES had been performed successfully in a series of surgical procedures including salpingectomy, ovarian cystectomy, myomectomy, hysterectomy, lymphadenectomy and sacrocolpopexy. Advances in technology have improved the feasibility of vNOTES as a treatment option for gynecologic surgeries. When the technical limitations are overcome, wide application of vNOTES is expected to increase. Further prospective and comparative studies are needed to clarify the application of the techniques in gynecologic surgeries.

Background: The mechanism underlying cervical carcinogenesis that is mediated by persistent human papillomavirus (HPV) infection remains elusive.Aims: Here, for the first time, we deciphered both the temporal transition and spatial distribution of cellular subsets during disease progression from normal cervix tissues to precursor lesions to cervical cancer.Materials & Methods: We generated scRNA‐seq profiles and spatial transcriptomics data from nine patient samples, including two HPV‐negative normal, two HPV‐positive normal, two HPV‐positive HSIL and three HPV‐positive cancer samples.Results: We not only identified three ‘HPV‐related epithelial clusters’ that are unique to normal, high‐grade squamous intraepithelial lesions (HSIL) and cervical cancer tissues but also discovered node genes that potentially regulate disease progression. Moreover, we observed the gradual transition of multiple immune cells that exhibited positive immune responses, followed by dysregulation and exhaustion, and ultimately established an immune‐suppressive microenvironment during the malignant program. In addition, analysis of cellular interactions further verified that a ‘homeostasis‐balance‐malignancy’ change occurred within the cervical microenvironment during disease progression.Discussion: We for the first time presented a spatiotemporal atlas that systematically described the cellular heterogeneity and spatial map along the four developmental steps of HPV‐related cervical oncogenesis, including normal, HPV‐positive normal, HSIL and cancer. We identified three unique HPV‐related clusters, discovered critical node genes that determined the cell fate and uncovered the immune remodeling during disease escalation.Conclusion: Together, these findings provided novel possibilities for accurate diagnosis, precise treatment and prognosis evaluation of patients with precancer and cervical cancer.

Cervical cancer (CC) is the fourth leading cause of deaths in gynecological malignancies. Although the etiology of CC has been extensively investigated, the exact pathogenesis of CC remains incomplete. Recently, single-cell technologies demonstrated advantages in exploring intra-tumoral diversification among various tumor cells. However, single-cell transcriptome analysis (single-cell RNA sequencing [scRNA-seq]) of CC cells and microenvironment has not been conducted. In this study, a total of 20,938 cells from CC and adjacent normal tissues were examined by scRNA-seq. We identified four tumor cell subpopulations in tumor cells, which had specific signature genes with different biological functions and presented different prognoses. Among them, we identified a subset of cancer stem cells (CSCs) that was related to the developmental hierarchy of tumor progression. Then, we compared the expressive differences between tumor-derived endothelial cells (TECs) and normal ECs (NECs) and revealed higher expression of several metabolism-related genes in TECs. Then, we explored the potential biological function of ECs in vascularization and found several marker genes, which played a prior role in connections between cancer cells and ECs. Our findings provide valuable resources for deciphering the intra-tumoral heterogeneity of CC and uncover the developmental procedure of ECs, which paves the way for CC therapy.

Cervical cancer (CC) is the most common gynecological malignancy, whose cellular heterogeneity has not been fully understood. Here, we performed single-cell RNA sequencing (scRNA-seq) to survey the transcriptomes of 57,669 cells derived from three CC tumors with paired normal adjacent non-tumor (NAT) samples. Single-cell transcriptomics analysis revealed extensive heterogeneity in malignant cells of human CCs, wherein epithelial subpopulation exhibited different genomic and transcriptomic signatures. We also identified cancer-associated fibroblasts (CAFs) that may promote tumor progression of CC, and further distinguished inflammatory CAF (iCAF) and myofibroblastic CAF (myCAF). CD8⁺ T cell diversity revealed both proliferative (MKI67⁺) and non-cycling exhausted (PDCD1⁺) subpopulations at the end of the trajectory path. We used the epithelial signature genes derived from scRNA-seq to deconvolute bulk RNA-seq data of CC, identifying four different CC subtypes, namely hypoxia (S-H subtype), proliferation (S-P subtype), differentiation (S-D subtype), and immunoactive (S-I subtype) subtype. The S-H subtype showed the worst prognosis, while CC patients of the S-I subtype had the longest overall survival time. Our results lay the foundation for precision prognostic and therapeutic stratification of CC.