Xiaoqing Guo

Tumor Cell‐Expressed Herpesvirus Entry Mediator Regulates Proliferation and Adaptive Immunity in Ovarian Cancer

ABSTRACT Background Ovarian cancer (OvCa) is a prevalent gynecological malignancy with an increasing incidence and high mortality rate. Although the role of the herpesvirus entry mediator (HVEM), encoded by the TNFRSF14 gene, is currently considered pivotal in various types of cancer, the regulation of tumor cell‐expressed HVEM in OvCa remains inadequately understood. Methods Specimens were used to detect HVEM expression via quantitative RT‐PCR and flow cytometry. The proliferation of the murine OvCa cell line ID8 was determined using the Cell Counting Kit‐8, colony formation, and EdU staining assays. The immune constituents within the ascites fluid and spleen of tumor‐bearing mice were analyzed by flow cytometry. Bioinformatics analysis was performed to explore cytokines, chemokines, and signaling pathways regulated by HVEM, and differential expression levels were confirmed via quantitative RT‐PCR and western blot analysis. Results Herein, we identified a significant upregulation of HVEM in OvCa tissues compared with that in benign tissues and observed dominant expression of HVEM in CD45⁻EpCAM⁺ subsets in OvCa specimens. Tumor cell‐expressed HVEM was found to promote OvCa cell proliferation by partly activating spliced X‐box‐binding protein 1 (XBP1s)‐c‐Myc signaling. In mouse models, knockdown of Tnfrsf14 in ID8 cells alleviated OvCa progression and specifically affected the frequency and function of T cells in the ascites fluid and spleen. In addition, tumor cell‐expressed HVEM altered chemokine expression (CXCL1/9/10/11 and CCL2/4/5) and STAT signal activation (STAT5 and STAT6) in ID8 cells. Conclusion This study investigated the effects of HVEM on OvCa and validated its potential as a therapeutic marker for treating OvCa.

The impact of surgery–radiotherapy interval on prognosis in high-risk endometrial cancer patients: A single-center retrospective analysis

This study aims to investigate the impact of surgery–radiotherapy (S–RT) interval on the prognosis of high-risk endometrial cancer (EC) patients receiving postoperative adjuvant therapy. It evaluates the effect of different interval times on disease-free survival (DFS) to provide clinical treatment recommendations. This retrospective study included 150 high-risk EC patients who underwent surgery at our hospital between February 2021 and February 2023. Patients were categorized into 3 groups based on the S–RT interval: short interval (1–4 weeks), medium interval (5–8 weeks), and long interval (>8 weeks). Baseline data, treatment characteristics, and follow-up data were collected and analyzed. Primary outcomes included DFS and the effect of S–RT interval on DFS. Kaplan–Meier method was used for survival analysis, and multivariate Cox regression model – adjusting for key confounding factors such as age, Fédération Internationale de Gynécologie et d'Obstétrique stage, pathological type, deep myometrial invasion, lymphovascular space invasion (LVSI), and lymph node metastasis – was applied to evaluate independent prognostic factors. The 2-year DFS rate for the short interval group was 55%, significantly higher than the medium interval group (49%) and long interval group (24%), with statistically significant differences between the groups ( P  < .001). Cox regression analysis indicated that the S–RT interval is an independent prognostic factor for DFS, with the long interval (>8 weeks) group showing a significantly increased risk of recurrence compared to the short interval group (HR = 1.9, 95% CI: 1.4–2.5, P  < .001). Pathological features such as deep myometrial invasion, LVSI positivity, and lymph node metastasis were also independent prognostic factors. The timing of postoperative radiotherapy initiation significantly affects prognosis in high-risk EC patients, even after adjusting for key clinical and pathological variables. Delayed radiotherapy (>8 weeks) markedly increases recurrence risk. These findings suggest that shortening the S–RT interval may improve DFS. However, the results need to be validated in larger sample sizes and multi-center prospective studies before generalization.

Suppressor of TCR signaling 2 (Sts-2) as a potential immunotherapy target and prognostic biomarker in cervical cancer

More efficient immune targets are needed for the treatment of cervical cancer. This study aimed to identify potential targets for immunotherapy and prediction in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) by conducting bioinformatics analysis and verifying the results with clinical tissue samples. A retrospective analysis of RNA sequencing data from 304 patients sourced from The Cancer Genome Atlas (TCGA) and another 300 patients from the Gene Expression Omnibus (GEO) was performed to investigate the correlation between suppressor of TCR signaling 2 (Sts-2) expression and clinical parameters in cervical cancer. To authenticate our findings, we utilized a combination of immunohistochemistry, quantitative polymerase chain reaction, and western blotting techniques in a separate cohort consisting of 6 cervical cancer tissue samples. The Sts-2 gene was discovered to be substantially co-expressed with a multitude of immune checkpoint molecules, including programmed cell death protein 1 (r=0.8, p<0.001), TIGIT (r=0.87, p<0.001), LAG3 (r=0.71, p<0.001), and CTLA4 (r=0.74, p<0.001), in CESC patients. Both the TCGA and GEO datasets have independently validated that Sts-2 expression levels significantly correlate with overall survival rates, thus demonstrating its prognostic importance. A single-gene Gene Set Enrichment Analysis indicated that Sts-2 was highly enriched in T cell-related immune pathways. Moreover, using the Tumor Immune Dysfunction and Exclusion algorithm, it was suggested that high Sts-2 expression might predict a more favorable response to immunotherapy. The heightened expression of Sts-2 serves as a dual indicator of elevated T cell content and a favorable prognosis in cervical cancer.

Intraoperative frozen section pathology of vaginal margin in radical hysterectomy on the prognosis and quality of life for patients with IB2–IIA2 cervical cancer: study protocol for a multicenter randomized controlled trial

Several risk factors have been identified that compromise the treatment outcome in patients with early-to-mid-stage cervical cancer (CC) who are primarily treated with radical surgery. However, there is no report on the impact of intraoperative frozen pathology examination of vaginal margins on the prognosis of patients with CC. This study aimed to conduct a randomized controlled trial (RCT) to determine whether selective vaginal resection can reduce the incidence of operative complications and the risk of postoperative radiotherapy. The impact of the length of the vagina removed in radical hysterectomy (RH) on prognosis and quality of life (QoL) for IB2-IIA2 CC patients will be investigated. A multicenter, non-inferiority, RCT at 7 institutions in China is designed to investigate the effect of intraoperative frozen pathology exam of vaginal margin in RH on the survival outcomes for patients with IB2-IIA2 CC. Eligible patients aged 18-70 years will be randomly assigned online by one-to-one random allocation to receive intraoperative frozen pathology exam of vaginal margin or not. If frozen pathology indicates positive margin, continue resection of 1 centimeter of vaginal tissue until negative margin is achieved. The primary end point is 2-year disease-free survival (DFS). Adverse events (AEs) caused by further vagina resection, 5-year DFS, 2-year overall survival (OS), 5-year OS and AEs caused by radiotherapy and QoL are secondary end points. A total of 310 patients will be enrolled from 7 tertiary hospitals in China within 3-year period and followed up for 5 years. Chinese Clinical Trial Registry Identifier: ChiCTR2000035668.

Myeloid‐derived suppressor cells promote epithelial ovarian cancer cell stemness by inducing the CSF2/p‐STAT3 signalling pathway

Myeloid‐derived suppressor cells (MDSCs) are known to contribute to tumour immune evasion, and studies have verified that MDSCs can induce cancer stem cells (CSCs) and promote tumour immune evasion in breast cancers, cervical cancers and glioblastoma. However, the potential function of MDSCs in regulating CSCs in epithelial ovarian cancer (EOC) progression is unknown. Our results indicated that compared to nonmalignant ovarian patients, EOC patients showed a significantly increased proportion of MDSCs in the peripheral blood. In addition, MDSCs dramatically promoted tumour sphere formation, cell colony formation and CSC accumulation, and MDSCs enhanced the expression of the stemness biomarkers NANOG and c‐MYC in EOC cells during coculture. Moreover, the mechanisms by which MDSCs enhance EOC stemness were further explored, and 586 differentially expressed genes were found in EOC cells cocultured with or without MDSCs; during coculture, the expression level of colony‐stimulating factor 2 (CSF2) was significantly increased in EOC cells cocultured with MDSCs. Furthermore, the depletion of CSF2 in EOC cells was successfully performed, the promotive effects of MDSCs on EOC cell stemness could be markedly reversed by downregulating CSF2 expression, p‐STAT3 signalling pathway molecules were also altered, and the p‐STAT3 inhibitor could markedly reverse the promotive effects of MDSCs on EOC cell stemness. In addition, the CSF2 expression level was correlated with EOC clinical staging. Therefore, MDSCs enhance the stemness of EOC cells by inducing the CSF2/p‐STAT3 signalling pathway. Targeting MDSCs or CSF2 may be a reasonable strategy for enhancing the efficacy of conventional treatments.DatabaseGene expression data files are available in the GEO databases under the accession number(s) GSE145374.

Intraoperative frozen pathology exam of Common iliac lymph nodes and Para-Aortic lymphadenectomy on the prognosis and quality of life for patients with IB2-IIA2 Cervical Cancer: trial protocol for a randomized controlled trial (C-PACC trial)

The impact of para-aortic lymphadenectomy (PALD) on prognosis and quality of life (QoL) for IB2-IIA2 cervical cancer patients remain controversial. And whether intraoperative frozen pathology exam on common iliac lymph nodes could help predict para-aortic lymph node (PALN) metastasis was unanswered with high-level evidence. A multi-center, randomized controlled study is intended to investigate the effect of PALD on the prognosis and QoL in cervical cancer patients and to assess the value of intraoperative frozen pathological evaluation of common iliac nodes metastasis for the prediction of PALN metastasis. After choosing whether to receive intraoperative frozen pathological examination of bilateral common iliac lymph nodes, eligible patients will be randomly assigned (1:1) to receive PALD or not. The primary end point is 2-year progression-free survival (PFS). The secondary end points include 5-year PFS, 2-year overall survival (OS), 5-year OS, adverse events (AEs) caused by PALD, AEs caused by radiotherapy and QoL. A total of 728 patients will be enrolled from 8 hospitals in China within 3-year period and followed up for 5 years. Chinese Clinical Trial Register Identifier: ChiCTR2000035668.