Identification and Validation of a PEX5-Dependent Signature for Prognostic Prediction in Glioma.

Gliomas, the most prevalent and lethal form of brain cancer, are known to exhibit metabolic alterations that facilitate tumor growth, invasion, and resistance to therapies. Peroxisomes, essential organelles responsible for fatty acid oxidation and reactive oxygen species (ROS) homeostasis, rely on the receptor PEX5 for the import of metabolic enzymes into their matrix. However, the prognostic significance of peroxisomal enzymes for glioma patients remains unclear. In this study, we elucidate that PEX5 is indispensable for the cell growth, migration, and invasion of glioma cells. We establish a robust prognosis model based on the expression of peroxisomal enzymes, whose localization relies on PEX5. This PEX5-dependent signature not only serves as a robust prognosis model capable of accurately predicting outcomes for glioma patients, but also effectively distinguishes several clinicopathological features, including the grade, isocitrate dehydrogenase (IDH) mutation, and 1p19q codeletion status. Furthermore, we developed a nomogram that integrates the prognostic model with other clinicopathological factors, demonstrating highly accurate performance in estimating patient survival. Patients classified into the high-risk group based on our prognostic model exhibited an immunosuppressive microenvironment. Finally, our validation reveals that the elevated expression of GSTK1, an antioxidant enzyme within the signature, promotes the cell growth and migration of glioma cells, with this effect dependent on the peroxisomal targeting signal recognized by PEX5. These findings identify the PEX5-dependent signature as a promising prognostic tool for gliomas.

A novel EGFR variant EGFRx maintains glioblastoma stem cells through STAT5.

BACKGROUND: Glioblastomas are universally lethal brain tumors containing tumor-propagating glioblastoma stem cells (GSCs). EGFR gene amplification or mutation is frequently detected in GBMs and is associated with poor prognosis. However, EGFR variants in GSCs and their role in the maintenance of GSCs and progression of GBM are unclear. METHODS: EGFR variants were detected through bioinformatic HISAT-StringTie-Ballgown pipeline and verified through 5' RACE, RT-PCR, ribonuclease protection, and northern blotting assays. EGFRx function was investigated through neurosphere, cell viability, intracranial xenograft and RNA-seq assays. EGFRx-STAT5 signaling was investigated through western blotting, coimmunoprecipitation, immunofluorescence, luciferase reporter, RT-PCR and CUT&Tag assays. RESULTS: We identified a novel EGFR variant (EGFRx), that is specifically expressed in GSCs. Unlike the EGFRvIII variant, which lacks exons 2-7, EGFRx is characterized by the absence of exons 2-14, and encodes an EGFR protein that does not possess the entire extracellular ligand-binding domain. We observed that EGFRx exhibits significant glycosylation, is required for GSC self-renewal, proliferation, and tumorigenesis, and highly active in glioblastomas compared to normal brain tissue. Mechanistically, EGFRx constitutively and specifically activates STAT5 in GSCs through spontaneous asymmetric dimerization of the kinase domain. CONCLUSIONS: EGFRx plays essential roles in the maintenance of the GSC phenotype through constitutive activation of STAT5 and promotes GBM progression, suggesting that EGFRx-STAT5 signaling represents a promising therapeutic target for GBM.

An improvement in the reconstruction of digestive tract after total gastrectomy: ultra-short cecum.

Aim: This study aimed to evaluate the utility and complications of ultra-short cecum (USC) in the reconstruction of digestive tract after total gastrectomy (TG) for the alleviation of reflux esophagitis and to determine its effect on long-term nutritional status. Methods: Patients who underwent TG with USC or normal cecum (NC) at a single institution between June 2018 and December 2020 were included in this study. The inclusion and exclusion criteria were defined, and the primary endpoints were reflux esophagitis, anastomotic leakage and postoperative nutritional status. The long-term nutritional status was evaluated by the change trend of laboratory blood tests, including total protein, prealbumin, hemoglobin, and total leukocytes. Results: Totally 240 cases were included in the final analysis out of 496 patients who received TG with USC or NC. Postoperative reflux esophagitis was significantly higher in the NC group than in the USC group (24.7% versus 7.7%, P = 0.001), and the NC group had a higher incidence of severe esophagitis symptoms compared to the USC group (13.6% versus 0.00%, P < 0.001), and the incidence of anastomotic leakage in the USC group was similar to that in the NC group (9.0% versus 6.2%, P = 0.6). There was no significant difference in long-term nutritional status between the USC and NC groups in the two years following the surgery (P > 0.05). Conclusion: Ultra-short cecum after total gastrectomy should be more actively recommended due to its significant reduction in reflux esophagitis and similar incidence of anastomotic leakage and nutritional status compared with normal cecum after total gastrectomy.

Laparoscopic versus Open Approach for Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction: A Systematic Review and Meta-Analysis.

INTRODUCTION: Due to the specific location, the potential advantages of laparoscopic gastrectomy (LG) compared with open gastrectomy (OG) for Siewert II/III adenocarcinoma of the esophagogastric junction (AEG) remain uncertain. The current study aimed to compare the short- and long-term outcomes of LG versus OG in treating Siewert type II/III adenocarcinoma. METHODS: We searched PubMed, Embase, Web of Science, MEDLINE (hosted by Ovid), and the Cochrane Library for publications till July 2022 and then used the RevMan 5.3 software for statistical analysis. RESULTS: Ten publications from 10 medical centers were included, with 1,516 cases from the LG group and 1,219 from the OG group. Meta-analysis results showed that the LG group was superior to the OG group in intraoperative blood loss, hospital stay, lymph nodes retrieved, time to ambulation, time to first flatus, time to diet, 5-year overall survival, and 5-year disease-free survival. There was no significant difference between the two groups in operative time, overall complications, proximal margin, distal margin, pulmonary infection, anastomotic leakage, mortality, ileus, or absolute infection. CONCLUSIONS: Compared with OG, LG is associated with better surgical and long-term outcomes in Siewert type II/III AEG. LG is a safe and feasible option for treating Siewert type II/III AEG. However, studies with large sample sizes, long follow-up periods, and rigorous designs are needed for verification.