ABSTRACT
BACKGROUND: Periprostatic adipose tissue (PPAT) plays a role in prostate cancer (PCa) progression. PPAT lipidomic composition study may allow us to understand the tumor metabolic microenvironment and provide new stratification factors. METHODS: We used ultra-high-performance liquid chromatography-mass spectrometry-based non-targeted lipidomics to profile lipids in the PPAT of 40 patients with PCa (n = 20 with low-risk and n = 20 high-risk). Partial least squares-discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify the most relevant features of PPAT between low- and high-risk PCa, and metabolite set enrichment analysis was used to detect disrupted metabolic pathways. Metabolic crosstalk between PPAT and PCa cell lines (PC-3 and LNCaP) was studied using ex vivo experiments. Lipid uptake and lipid accumulation were measured. Lipid metabolic-related genes (SREBP1, FASN, ACACA, LIPE, PPARG, CD36, PNPLA2, FABP4, CPT1A, FATP5, ADIPOQ), inflammatory markers (IL-6, IL-1B, TNFα), and tumor-related markers (ESRRA, MMP-9, TWIST1) were measured by RT-qPCR. RESULTS: Significant differences in the content of 67 lipid species were identified in PPAT samples between high- and low-risk PCa. PLS-DA and VIP analyses revealed a discriminating lipidomic panel between low- and high-risk PCa, suggesting the occurrence of disordered lipid metabolism in patients related to PCa aggressiveness. Functional analysis revealed that alterations in fatty acid biosynthesis, linoleic acid metabolism, and ß-oxidation of very long-chain fatty acids had the greatest impact in the PPAT lipidome. Gene analyses of PPAT samples demonstrated that the expression of genes associated with de novo fatty acid synthesis such as FASN and ACACA were significantly lower in PPAT from high-risk PCa than in low-risk counterparts. This was accompanied by the overexpression of inflammatory markers (IL-6, IL-1B, and TNFα). Co-culture of PPAT explants with PCa cell lines revealed a reduced gene expression of lipid metabolic-related genes (CD36, FASN, PPARG, and CPT1A), contrary to that observed in co-cultured PCa cell lines. This was followed by an increase in lipid uptake and lipid accumulation in PCa cells. Tumor-related genes were increased in co-cultured PCa cell lines. CONCLUSIONS: Disturbances in PPAT lipid metabolism of patients with high-risk PCa are associated with tumor cell metabolic changes.
Subject(s)
Lipidomics , Tumor Necrosis Factor-alpha , Adipose Tissue/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Fatty Acids , Humans , Interleukin-6 , Lipids , Male , PPAR gamma/metabolismABSTRACT
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Subject(s)
Humans , Female , Middle Aged , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/radiotherapy , Carcinoma, Neuroendocrine/surgery , Tongue Neoplasms/diagnosis , Tongue Neoplasms/radiotherapy , Tongue Neoplasms/surgery , Oropharyngeal Neoplasms/diagnosis , Tomography, X-Ray Computed , Drug Therapy/methods , Radiotherapy/methodsSubject(s)
Carcinoma, Small Cell/diagnosis , Tongue Neoplasms/diagnosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/radiotherapy , Carcinoma, Small Cell/secondary , Cisplatin/administration & dosage , Combined Modality Therapy , Epiglottis/pathology , Etoposide/administration & dosage , Fatal Outcome , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness , Radiotherapy, Intensity-Modulated , Smoking/adverse effects , Tongue Neoplasms/drug therapy , Tongue Neoplasms/pathology , Tongue Neoplasms/radiotherapyABSTRACT
Antecedentes. La mucormicosis (zigomicosis) cutánea con extensión subcutánea y diseminación en pacientes inmunocompetentes es una patología infrecuente causada por especies de los géneros Apophysomyces, Rhizopus y Saksenaea, entre otros. Caso clínico. Se describe un caso de fascitis necrotizante por Saksenaea vasiformis en una mujer inmunocompetente, que sufrió politraumatismo y herida en brazo derecho a consecuencia de un accidente de tráfico. Tras la reducción quirúrgica de las fracturas, la lesión cutánea fue empeorando y derivó en necrosis y fascitis necrotizante grave con cultivos inicialmente negativos. A pesar de la amplia resección quirúrgica y el tratamiento antifúngico agresivo, el desenlace fue la muerte de la paciente. El estudio histopatológico puso en evidencia una infección por un hongo del orden Mucorales, confirmada mediante aislamiento primario en agar Sabouraud y posterior identificación de la especie mediante cultivo en agar Czapek-Dox y secuenciación de la región ITS del ADN ribosomal. Conclusiones. El presente caso confirma la presencia de este hongo en nuestro país, además de la utilidad del estudio histopatológico para el diagnóstico de la mucormicosis, y de los medios de cultivo especiales y las técnicas moleculares para la identificación de la especie(AU)
Background. Cutaneous mucormycosis (zygomycosis), with subcutaneous spreading and dissemination, in immunocompetent patients is an uncommon disease caused by species belonging to the fungal genera Apophysomyces, Rhizopus and Saksenaea, among others. Case report. A case of necrotising fasciitis by Saksenaea vasiformis in an immunocompetent woman is described. The infection was acquired through a car accident resulting in multiple injuries affecting mainly her right arm. After the surgical reduction of fractures, skin lesions worsened and led to necrosis. The patient quickly developed a severe necrotising fasciitis with negative cultures at first. Despite the extensive surgical debridement and the aggressive antifungal treatment, the patient died. The histopathological study showed a fungal infection due to a fungus belonging to the Mucorales order, which was confirmed by culturing the clinical sample on Sabouraud agar, and identifying the species by cultures on Czapek-Dox agar, and sequencing of the ITS region of the ribosomal DNA. Conclusions. This case confirm the presence of this fungus in Spain, the value of histopathology for the mucormycosis diagnosis, as well as the need to perform special cultures to facilitate their isolation and identification to the species level by the combined use of Czapek-Dox agar and sequencing of the ITS region(AU)
Subject(s)
Female , Humans , Zygomycosis/diagnosis , Zygomycosis/microbiology , Rhizopus/isolation & purification , Fasciitis, Necrotizing/complications , Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/microbiology , Necrosis/complications , Necrosis/diagnosis , Zygomycosis/etiology , Zygomycosis/immunology , Zygomycosis/physiopathology , Necrosis/drug therapy , Necrosis/microbiology , Necrosis/physiopathologyABSTRACT
BACKGROUND: Cutaneous mucormycosis (zygomycosis), with subcutaneous spreading and dissemination, in immunocompetent patients is an uncommon disease caused by species belonging to the fungal genera Apophysomyces, Rhizopus and Saksenaea, among others. CASE REPORT: A case of necrotising fasciitis by Saksenaea vasiformis in an immunocompetent woman is described. The infection was acquired through a car accident resulting in multiple injuries affecting mainly her right arm. After the surgical reduction of fractures, skin lesions worsened and led to necrosis. The patient quickly developed a severe necrotising fasciitis with negative cultures at first. Despite the extensive surgical debridement and the aggressive antifungal treatment, the patient died. The histopathological study showed a fungal infection due to a fungus belonging to the Mucorales order, which was confirmed by culturing the clinical sample on Sabouraud agar, and identifying the species by cultures on Czapek-Dox agar, and sequencing of the ITS region of the ribosomal DNA. CONCLUSIONS: This case confirm the presence of this fungus in Spain, the value of histopathology for the mucormycosis diagnosis, as well as the need to perform special cultures to facilitate their isolation and identification to the species level by the combined use of Czapek-Dox agar and sequencing of the ITS region.
