Bilan Li

ARNTL-mediated INO80-DHX15 axis reprograms the glycolytic metabolism and augments the progression of endometrial carcinoma

Abstract Immune evasion is a major mechanism responsible for tumor cell survival and dissemination. This study aims to explore key molecules involved in immunosuppression and metastasis of endometrial carcinoma (EC). Primary and metastatic tumors were collected from four patients with EC for array analysis. Metastatic tumors exhibited increased macrophage infiltration, while decreased CD8+ T cell infiltration, and aryl hydrocarbon receptor nuclear translocator-like (ARNTL) was identified as a key factor involved. High ARNTL expression was linked to poor tumor differentiation, advanced stage, and increased metastasis in another cohort of 300 EC patients. ARNTL knockout (ARNTL-KO) in EC cells reduced cell proliferation, migration, and invasion, and increased cell death in vitro, and it blocked the tumorigenicity and metastatic activity of cells in mice. The ARNTL-KO EC cells reduced the M2 polarization of macrophages and induced CD8+ T cell proliferation both in vitro and in vivo. ARNTL activated the transcription of INO80 complex ATPase subunit (INO80), a chromatin remodeler, which further promoted the transcription of DEAH-box helicase 15 (DHX15) through histone acetylation modifications. Overexpression of either INO80 or DHX15 increased glycolytic activity and immunosuppression in ARNTL-KO EC cells. Collectively, this study suggests that the ARNTL-mediated INO80-DHX15 axis induces glycolysis and immunosuppression during EC progression.

The potential impact of RNA splicing abnormalities on immune regulation in endometrial cancer

Abstract RNA splicing controls the post-transcriptional level of gene expression, allowing for the synthesis of many transcripts with various configurations and roles. Variations in RNA splicing regulatory factors, including splicing factors, signaling pathways, epigenetic modifications, and environmental factors, are typically the origin of tumor-associated splicing anomalies. Furthermore, thorough literature assessments on the intricate connection between tumor-related splicing dysregulation and tumor immunity are currently lacking. Therefore, we also thoroughly discuss putative targets associated with RNA splicing in endometrial cancer (EC) and the possible impacts of aberrant RNA splicing on the immune control of tumor cells and tumor microenvironment (TME), which contributes to enhancing the utilization of immunotherapy in the management of EC and offers an alternative viewpoint for the exploration of cancer therapies and plausible prognostic indicators.

Prognostic significance of immune landscape in tumour microenvironment of endometrial cancer

AbstractTumour microenvironment (TME) is crucial to tumorigenesis. This study aimed to uncover the differences in immune phenotypes of TME in endometrial cancer (EC) using Uterine Corpus Endometrial Carcinoma (UCEC) cohort and explore the prognostic significance. We employed GVSA enrichment analysis to cluster The Cancer Genome Atlas (TCGA) EC samples into immune signature cluster modelling, evaluated immune cell profiling in UCEC cohort (n = 538) and defined four immune subtypes of EC. Next, we analysed the correlation between immune subtypes and clinical data including patient prognosis. Furthermore, we analysed the expression of immunomodulators and DNA methylation modification. The profiles of immune infiltration in TCGA UCEC cohort showed significant difference among four immune subtypes of EC. Among each immune subtype, natural killer T cells (NKT), dendritic cells (DCs) and CD8+T cells were significantly associated with EC patients survival. Each immune subtype exhibited specific molecular classification, immune cell characterization and immunomodulators expression. Moreover, the expression immunomodulators were significantly related to DNA methylation level. In conclusion, the identification of immune subtypes in EC tissues could reveal unique immune microenvironments in EC and predict the prognosis of EC patients.

Predictive value of hemoglobin, platelets, and D-dimer for the survival of patients with stage IA1 to IIA2 cervical cancer: a retrospective study

Objective Coagulation indexes may be useful survival biomarkers for cervical cancer. This study evaluated the ability of hemoglobin, red blood cells (RBCs), platelets, and D-dimer levels to predict post-hysterectomy survival outcomes in patients with stage IA1 to IIA2 cervical cancer. Methods In this retrospective study, coagulation-related indexes were compared between the anemia and non-anemia groups. Independent variables were analyzed by the Cox proportional hazards model. Survival was assessed by the Kaplan–Meier method with the log-rank test. Mortality predictions were evaluated by receiver operating characteristic curves. Results Among this study’s 1088 enrolled patients, 152 had anemia. The 10-year overall survival and recurrence-free survival rates were 90.8% and 86.5%, respectively. Hemoglobin, RBC, and the rate of abnormal platelet counts were significantly lower in the anemia group. Abnormal preoperative D-dimer was an independent factor for recurrence-free survival. Receiver operating characteristic curves showed that D-dimer had area under the curve of 0.734 (cut-off value: 0.685, sensitivity: 85.7%, and specificity: 64.0%). Hemoglobin and platelets had areas under the curves of 0.487 and 0.462, respectively. Conclusion Preoperative D-dimer was the most effective prognostic predictor for patients with cervical cancer. The prognosis of patients with cervical cancer was poorer if their D-dimer levels were >0.685 mg/L.