Background: To discover biomarker panels that could distinguish cancers (BC and RCC) from healthy controls (HCs) and bladder cancers (BC) from renal cell carcinoma (RCC), regardless of whether the patients have haematuria. In addition, we also explored the altered metabolomic pathways of BC and RCC. Methods: In total, 403 participants were enrolled in our study, which included 146 BC patients (77 without haematuria and 69 with haematuria), 115 RCC patients (94 without haematuria and 21 with haematuria) and 142 sex- and age-matched HCs. Their midstream urine samples were collected and analysed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarker panels and altered metabolic pathways. Results: The panel of α-CEHC, β-cortolone, deoxyinosine, flunisolide, 11b,17a,21-trihydroxypreg-nenolone and glycerol tripropanoate could distinguish the patients with cancer from the HCs (the AUC was 0.950) and the external validation also displayed a good predictive ability (the AUC was 0.867). The panel of 4-ethoxymethylphenol, prostaglandin F2b, thromboxane B3, hydroxybutyrylcarnitine, 3-hydroxyphloretin and N′-formylkynurenine could differentiate BC from RCC without haematuria. The AUC was 0.829 in the discovering group and 0.76 in the external validation. The metabolite panel comprising 1-hydroxy-2-oxopropyl tetrahydropterin, 1-acetoxy-2-hydroxy-16-heptadecyn-4-one, 1,2-dehydrosalsolinol and L-tyrosine could significantly discriminate BC from RCC with haematuria (AUC was 0.913). Pathway analyses revealed altered lipid and purine metabolisms between cancer patients and HCs, together with disordered amino acid and purine metabolisms between BC and RCC with haematuria. Conclusions: UPLC-MS urine metabolomic analyses could not only differentiate cancers from HCs but also discriminate BC from RCC. In addition, pathway analyses demonstrated a deeper metabolic mechanism of BC and RCC.

Background: Bladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide. Prognostic biomarkers for bladder cancer patients are required for individualized treatment. Monocarboxylate transporter 4 (MCT4), encoded by SLC16A3 gene, is a potential biomarker for bladder cancer because of its crucial role in the lactate efflux in the aerobic glycolysis process. We aimed to study the association between MCT4 expression and the overall survival (OS) of bladder cancer patients.Methods: The published single-cell RNA sequencing data of 49,869 bladder cancer cells and 15,827 normal bladder mucosa cells and The Cancer Genome Atlas (TCGA) bladder cancer cohort data were used to explore the mRNA expression of SLC16A3 in bladder cancer. Eighty-nine consecutive bladder cancer patients who had undergone radical cystectomy were enrolled as a validation cohort. The expression of MCT4 proteins in bladder cancer specimens was detected using immunohistochemistry staining. The Kaplan–Meier survival analysis and Cox regression were performed to analyze the association between MCT4 protein expression and OS in bladder cancer patients.Results: SLC16A3 mRNA was upregulated in bladder cancer cells. The upregulated genes in SLC16A3-positive epithelial cells were enriched in the glycolysis process pathway and monocarboxylic acid metabolic process pathway. Patients with high SLC16A3 mRNA expression showed significantly poor OS (p = 0.016). High MCT4 protein expression was also found to be an independent predictor for poor OS in bladder cancer patients (HR: 2.462; 95% CI: 1.202~5.042, p = 0.014). A nomogram was built based on the results of the multivariate Cox analysis.Conclusion: Bladder cancer with high SLC16A3 mRNA expression has a poor OS. High MCT4 protein expression is an independent prognostic factor for bladder cancer patients who had undergone radical cystectomy.

Background: Radiofrequency ablation (RFA) is the primary curative treatment for hepatocellular carcinoma (HCC) patients who are not eligible for surgery. However, the effects of RFA on the global tumor immune response remain unclear.Method: In this study, we examined the phenotypic and functional changes in peripheral blood mononuclear cells (PBMCs) from recurrent HCC patients who had undergone two RFA treatments using mass cytometry and high-throughput mRNA assays. Results: We observed significant increase in monocytes and decrease in T cell subpopulations three days after the first RFA treatment and three days after the second RFA treatment. The down-regulation of GZMB, GZMH, GZMK, and CD8A, which are involved in the cytotoxic function of T cells, was observed following RFA. Furthermore, the population of CD8 effector and memory T cells (CD8 Teff and CD8 Tem) significantly decreased after RFA. The expression of CD5 and CD161 in various T cell subpopulations also showed significant reductions. Additionally, elevated secretion of VEGF was observed in monocytes, B cells, regulatory T cells (Tregs), and CD4 naive T cells. Conclusion: In recurrent HCC patients, serum components derived from radiofrequency therapy can enhance the antigen-presenting capacity of monocytes. However, they also inhibit the anti-cancer immune response by reducing the population of CD8 effector and memory T cells and suppressing the activation of T cells, as well as down-regulating the expression of CD161 and CD5 in various T cell subpopulations. These tumor-derived components also contribute to an immunosuppressive microenvironment by promoting the secretion of VEGF in monocytes, Tregs, B cells, and CD4 naive T cells.

Tuberous sclerosis complex (TSC) is a rare disease that threatens multiple organs in the human body. TSC‑associated renal angiomyolipoma (TSC‑RAML) has potentially life‑threatening complications and a generally poor prognosis. The present study aimed to find plasma proteomic diagnostics and disease‑associated markers, and explore the tumor microenvironment using multi‑omics. To achieve this goal, the plasma proteomics as well as tissue proteomics, bulk and single‑cell RNA transcriptome from patients with TSC‑RAML were examined and analyzed. The results suggested that plasma proteins such as MMP9 and C‑C motif chemokine ligand 5 were able to differentiate TSC‑RAML from sporadic angiomyolipoma and renal cyst. A correlation analysis revealed that plasma proteomics were associated with lymphangioleiomyomatosis, TSC‑RAML grading and whole‑body disease burden. Tissue proteomics of participants with TSC‑RAML revealed disturbed small molecule catabolic process, mitochondrial matrix component and actin binding function. Bulk and single‑cell RNA sequencing suggested a greater number of tumor‑like cells, fibroblasts and mononuclear macrophages within the tumor microenvironment. The above results indicated that TSC‑RAML exhibited a characteristic and disease‑associated plasma proteomic profile. The unique microenvironment, made up of fibroblasts and mono‑macrophages, may promote tumorigenesis and TSC‑RAML progression.

Pheochromocytomas (PCC)/paragangliomas (PGL) are catecholamine (CA) -secreting neuroendocrine tumors, which are known as PPGL due to their histological and pathophysiological similarities. In addition to the typical triad of paroxysmal headache, palpitation, and sweating, PPGL may also be accompanied by symptoms and signs involving multiple organs and systems such as the cardiovascular system, digestive system, endocrine system, and nervous system. Currently, surgical resection is the first choice for PPGL. Safe and effective surgical management of complicated PPGL is the goal of clinical work. In this paper, we discuss this hot issue based on complicated PPGL cases, aiming to share our experience of the surgical management strategy of PPGL.