Investigator
Huazhong University Of Science And Technology
Fucoxanthin from Laminaria japonica Targeting PANoptosis and Ferroptosis Pathways: Insights into Its Therapeutic Potential Against Ovarian Cancer
Ovarian cancer (OC) is a highly aggressive malignancy with a poor prognosis, necessitating novel therapeutic strategies. Fucoxanthin (FX), a marine-derived carotenoid from Laminaria japonica, has demonstrated promising anticancer potential. This study revealed that FX exerts multiple anticancer effects in OC by inhibiting cell proliferation, invasion, and migration, while inducing various forms of programmed cell death (PCD). FX triggered PANoptosis (apoptosis, necroptosis, and pyroptosis) and ferroptosis. FX treatment regulated key markers associated with PANoptosis, including apoptosis (Bcl-2, cleaved caspase-3), pyroptosis (GSDME), and necroptosis (RIPK3). Additionally, FX treatment modulated ferroptosis-related markers, such as SLC7A11 and GPX4, while increasing reactive oxygen species (ROS) and Fe2+ levels and disrupting mitochondrial function. Proteomic and molecular docking analyses identified AMP-activated protein kinase (AMPK) as a direct FX target, activating the AMPK/Nrf2/HMOX1 pathway to promote ferroptosis. In vivo, FX significantly reduced tumor growth in OC xenograft models, accompanied by enhanced ferroptosis marker expression. These findings demonstrate that FX induces ferroptosis through the AMPK/Nrf2/HMOX1 pathway and promotes PANoptosis via distinct mechanisms, highlighting its potential as a marine-derived therapeutic agent for OC.
Persistent and severe hypotension during radical transabdominal ovarian cancer surgery: A case report
Rationale: In radical surgery for ovarian cancer (OC), hypotension that is difficult to correct is usually rare unless there is significant blood loss. We recently encountered a patient who developed persistent and severe hypotension during radical transabdominal OC surgery. Patient concerns: A patient was 52 years old with a history of hypertension and well-controlled preoperative blood pressure (BP). A total of 2000 mL of ascites was drained and blood loss was 300 mL when the operation proceeded to 5.5 hours. The patient’s cardiopulmonary function and blood gas analysis showed no significant abnormalities. Diagnoses: persistent and uncorrectable hypotension. Interventions: There was no significant edema in the patient’s head or face, nor did the surgeon observe noticeable edema in her intestinal walls or other organs. No oozing was seen at the surgical site. Fluid resuscitation and vasopressor administration were continued. As BP control further deteriorated, blood counts, coagulation, and biochemical electrolyte analyses revealed severe hypoalbuminemia (13.5 g/L) and coagulation dysfunction. Outcomes: After intravenous human serum albumin (HSA) and fresh frozen plasma therapy, her hypoalbuminemia and coagulation were gradually corrected. Lessons: Based on this case, we suggest that in OC patients experiencing mild intraoperative bleeding and minimal heart rate variation but persistent refractory hypotension, hypoalbuminemia should be considered even if preoperative biochemical tests (including serum albumin levels) are normal. Confirming hypoalbuminemia warrants HSA administration to alleviate hypovolemic shock symptoms. Additionally, it is important to be cautious of potential coagulation issues with albumin use, possibly requiring plasma infusion to address coagulopathy.
Increased Expression of LYNX1 in Ovarian Serous Cystadenocarcinoma Predicts Poor Prognosis
Few studies have reported the function of LYNX1 in ovarian cancer. We retrieved LYNX1 gene expression data and clinical information of 376 patients with ovarian cancer from The Cancer Genome Atlas (TCGA) project website. Wilcoxon signed‐rank test and logistic regression were used to analyze the relationship between clinical pathologic features and LYNX1 expression. The Kaplan–Meier method was used to draw survival curves of patients, and Cox regression was used to calculate the relationship between LYNX1 expression and survival rate or the clinicopathological characteristics of the patients. Gene set enrichment analysis (GSEA) was performed, and the correlation between LYNX1 expression and cancer immune infiltrates was investigated via single sample gene set enrichment analysis (ssGSEA). High LYNX1 expression in ovarian serous cystadenocarcinoma (OVs) was associated with tumor residual disease (RD). In Kaplan–Meier survival analysis, patients with OVs who also displayed high LYNX1 expression had decreased overall survival (OS) and disease‐specific survival (DSS) than those with low LYNX1 expression. Univariate analysis also supported that patients with high LYNX1 expression had lower OS than those with low LYNX1 expression. LYNX1 expression has the potential to be a prognostic molecular marker of poor survival in OVs.
Long non-coding RNA FOXP4-AS1 is a prognostic biomarker and associated with immune infiltrates in ovarian serous cystadenocarcinoma
Abstract Background: FOXP4-AS1 expression participates in multiple signal pathways and has been previously reported in colorectal cancer, cervical cancer, and other cancer cells. However, its role on prognosis and immune infiltrates in ovarian serous cystadenocarcinoma (OVs) remains unclear. The purpose of our study was to investigate the expression of FOXP4-AS1 in OVs and its association with immune infiltrates, and determined its prognostic roles in OVs. Methods: Using The Cancer Genome Atlas (TCGA) database, we retrieved FOXP4-AS1 expression and clinical information for 376 patients with OVs. Wilcoxon rank sum test was used to compare the expression of FOXP4-AS1 in OVs and normal ovarian tissue. Logistic regression was used to analyze the relationship between clinicopathologic features and FOXP4-AS1. Gene Set Enrichment Analysis (GSEA), and single sample Gene Set Enrichment Analysis (ssGSEA) was conducted to investigate the enrich pathways and functions and quantify the extent of immune cells infiltration for FOXP4-AS1. Kaplan–Meier method was used to generate survival curves, and Cox regression was used to analyze the relationship between FOXP4-AS1 and survival rate. Results: High FOXP4-AS1 expression was significantly correlated with tumor FIGO stage (P = .026). Multivariate survival analysis showed that FOXP4-AS1was an independent prognostic marker for overall survival (OS; hazard ratio [HR]: 0.638; 95% confidence interval [CI]:0.467–0.871; P = .001) and disease-specific survival (DSS; HR: 0.649; CI: 0.476–0.885; P = .006). GSEA showed that High FOXP4-AS1 expression may active programmed cell death 1 (PD-1) signaling, the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) pathway, the B cell receptor signaling pathway, apoptosis, fibroblast growth factor receptor (FGFR) signaling, and the Janus-activated kinase signal transducers and activators of transcription (JAK-STAT) signaling pathway. FOXP4-AS1 expression was negatively correlated with markers of immune cells, including aDC, cytotoxic cells and neutrophils. Conclusion: High FOXP4-AS1 expression has the potential to be a prognostic molecular marker of favorable survival in OVs.
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