Background Bladder cancer (BLCA) is a highly malignant disease in the urinary system. Somatic mutation is a key feature in cancer occurrence, development, and treatment. Moreover, altered metabolism contributes to patient prognosis. However, the role of metabolism-related genes (MRGs) driven by somatic mutations in BLCA remains unclear. Methods The data were gathered from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The differentially expressed metabolism-related genes (DEMRGs) between normal and BLCA patients were first identified and the functions were discussed. Then The risk model was construct by the DEMRGs with mutation frequency. The accuracy of the risk model was verified by risk curves, Kaplan-Meier (K-M) curves, and Receiver Operating Characteristic (ROC) curves. Subsequently, the correlation of risk score and clinical traits was also researched. Gene Set Enrichment Analysis (GSEA), immune checkpoints, immune microenvironment, and chemotherapeutic drug sensitivity were performed in high- and low-risk groups. And the scRNA-seq revealed that the expression pattern of prognostic biomarkers and cellular heterogeneity. Eventually, the mRNA expression levels of biomarkers were validated by quantitative real-time PCR (qRT-PCR). Results A total of 201 DEMRGs were retrieved, and the DEMRGs were significantly enriched in alcohol metabolic process, cellular modified amino acid metabolic process, and purine metabolism. Then the 24 DEMRGs of the mutation frequency greater than 3% were further analyzed, and a risk model was constructed by 5 biomarkers (FASN, ABCC4, ATP2B4, ATP8B2, and MTHFD1L). Moreover, the AUCs were all greater than 0.6, indicating the risk model had good efficacy. Meanwhile, the riskScore, T-pathologic, age, and N-pathologic were regarded as independent prognostic indicators. The DEMRGs were enriched in OXIDATIVE_PHOSPHORYLATION. Three immune checkpoints, four types of immune cells, and 146 drugs were substantially different in the two risk groups. And the scRNA-seq further disclosed relationships between genes regulation and tracked the development trajectories of distinct cell lineages. Finally, qRT-PCR results showed the expression levels of FASN and MTHFD1L were significantly higher in carcinoma tissue. Conclusion In brief, this study constructed a novel biomarkers, which could improve the prediction of independent prognosis indicators and guide individualized treatment of BLCA patients.
Background Rapid lethal exacerbation and recurrence featuring acute leukemoid reaction (ALR) after retrolaparoscopic radical nephrectomy (RN) is a relatively rare clinical incident. Performing the reoperation for the patient and analyzing the tissue-based genetic mutation information postoperatively are a skill-demanding and meaningful task, which have been even more rarely reported. Case presentation We present a case with a large right renal mass (13.0 × 10.0 × 8.0 cm). This 71-year-old male patient underwent the retrolaparoscopic RN in our department. The operation was technically precise and successful with final pathological diagnosis of hybrid (clear cell and papillary type) renal cell carcinoma (RCC). However, 10 days after the patient was discharged, he was readmitted with the chief complaint of high fever with severe right flank pain. CT scanning revealed that right retroperitoneal hematoma and the blood routine showed the dramatic elevation of white blood cell count (WBC). Even though the immediate broad-spectrum antibiotics were administered without delay and subsequent percutaneous puncturing and drainage was performed, the patient’s condition still exacerbated rapidly. In spite of the reoperation of hematoma evacuation, the patient died of multiple organ failure 10 days after the reoperation. The pathological result of reoperation showed the necrotic and hematoma tissue blended with RCC tumor cells (nuclear grading III), and both of the postoperative tissue-originated comprehensive genomic profiling by using the specimens from the RN and reoperation respectively indicated significant mutations of some oncogenes which might have potential relevance with ALR. Besides, both of the immunohistochemical (IHC) staining results from primary surgical renal mass and reoperative resected tissue revealed the positive expressions of granulocyte colony-stimulating factor (G-CSF). Conclusions ALR may be a predictor of poor prognosis in patients with RCC, and comprehensive genomic profiling as well as the alterative expression of G-CSF can help to provide potential valuable genetic etiological information and evidence for guiding the potential effective molecular-targeting therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.