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1.
J Transl Med ; 22(1): 829, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39252063

RESUMEN

BACKGROUND: CT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach. METHOD: We utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P < 0.01) to overlap the co-expression genes of WGCNA module and M2 macrophages related genes (from mRNA data of 371 GC patients in TCGA database), generating a total of 136 genes. An EMVI-M2-prognosis-related hub gene signature was constructed by COX and least absolute shrinkage and selection operator (LASSO) analysis from a training cohort TCGA database (n = 371) and validated it in a validation cohort from GEO database (n = 357). High- and low-risk groups were divided by hub gene (EGFLAM and GNG11) signature-derived risk scores. We assessed its predictive ability through Kaplan-Meier (K-M) curve and COX analysis. Furthermore, we utilized ESTIMATE to detect tumor mutation burden (TMB) and evaluate sensitivity to immune checkpoint inhibitors (ICIs). Expression of hub genes was tested using western blotting and immunohistochemistry (IHC) analysis. RESULTS: The overall survival (OS) was significantly reduced in the high-risk group (Training/Validation: AUC = 0.701/0.620; P < 0.001/0.003). Furthermore, the risk score was identified as an independent predictor of OS in multivariate COX regression analyses (Training/Validation: HR = 1.909/1.928; 95% CI: 1.225-2.974/1.308-2.844). The low-risk group exhibited significantly higher TMB levels (P = 1.6e- 07) and greater sensitivity to ICIs. Significant higher expression of hub-genes was identified on multiple GC cell lines and original samples. Hub-genes knockdown in gastric cancer cell lines inhibited their proliferation, metastatic and invasive capacity to varying degrees. In vivo experiments indicate that EGFLAM, as one of the hub genes, its high expression can serve as a biomarker for low response to immunotherapy. CONCLUSION: Our study demonstrated EMVI-M2 gene signature could effectively predict the prognosis of GC tissue, reflecting the relationship between EMVI and M2 macrophages.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Macrófagos , Invasividad Neoplásica , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Estimación de Kaplan-Meier , Análisis de Supervivencia , Transcriptoma/genética , Animales , Línea Celular Tumoral , Perfilación de la Expresión Génica , Reproducibilidad de los Resultados , Anciano
2.
J Transl Med ; 21(1): 4, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36604653

RESUMEN

BACKGROUND: To investigate the association between computed tomography (CT)-detected extramural venous invasion (EMVI)-related genes and immunotherapy resistance and immune escape in patients with gastric cancer (GC). METHODS: Thirteen patients with pathologically proven locally advanced GC who had undergone preoperative abdominal contrast-enhanced CT and radical resection surgery were included in this study. Transcriptome sequencing was multidetector performed on the cancerous tissue obtained during surgery, and EMVI-related genes (P value for association < 0.001) were selected. A single-sample gene set enrichment analysis algorithm was also used to divide all GC samples (n = 377) in The Cancer Genome Atlas (TCGA) database into high and low EMVI-immune related groups based on immune-related differential genes. Cluster analysis was used to classify EMVI-immune-related genotypes, and survival among patients was validated in TCGA and Gene Expression Omnibus (GEO) cohorts. The EMVI scores were calculated using principal component analysis (PCA), and GC samples were divided into high and low EMVI score groups. Microsatellite instability (MSI) status, tumor mutation burden (TMB), response rate to immune checkpoint inhibitors (ICIs), immune escape were compared between the high and low EMVI score groups. Hub gene of the model in pan-cancer analysis was also performed. RESULTS: There were 17 EMVI-immune-related genes used for cluster analysis. PCA identified 8 genes (PCH17, SEMA6B, GJA4, CD34, ACVRL1, SOX17, CXCL12, DYSF) that were used to calculate EMVI scores. High EMVI score groups had lower MSI, TMB and response rate of ICIs, status but higher immune escape status. Among the 8 genes used for EMVI scores, CXCL12 and SOX17 were at the core of the protein-protein interaction (PPI) network and had a higher priority in pan-cancer analysis. Immunohistochemical analysis showed that the expression of CXCL12 and SOX17 was significantly higher in CT-detected EMVI-positive samples than in EMVI-negative samples (P < 0.0001). CONCLUSION: A CT-detected EMVI gene signature could be a potential negative biomarker for ICIs treatment, as the signature is negatively correlated with TMB, and MSI, resulting in poorer prognosis.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias Gástricas , Humanos , Biomarcadores de Tumor/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Invasividad Neoplásica/patología , Pronóstico , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Tomografía Computarizada por Rayos X
3.
Clin Exp Metastasis ; 41(2): 143-154, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38416301

RESUMEN

Chemotherapy alters the prognostic biomarker histopathological growth pattern (HGP) phenotype in colorectal liver metastases (CRLMs) patients. We aimed to develop a CT-based radiomics model to predict the transformation of the HGP phenotype after chemotherapy. This study included 181 patients with 298 CRLMs who underwent preoperative contrast-enhanced CT followed by partial hepatectomy between January 2007 and July 2022 at two institutions. HGPs were categorized as pure desmoplastic HGP (pdHGP) or non-pdHGP. The samples were allocated to training, internal validation, and external validation cohorts comprising 153, 65, and 29 CRLMs, respectively. Radiomics analysis was performed on pre-enhanced, arterial phase, portal venous phase (PVP), and fused images. The model was used to predict prechemotherapy HGPs in 112 CRLMs, and HGP transformation was analysed by comparing these findings with postchemotherapy HGPs determined pathologically. The prevalence of pdHGP was 19.8% (23/116) and 45.8% (70/153) in chemonaïve and postchemotherapy patients, respectively (P < 0.001). The PVP radiomics signature showed good performance in distinguishing pdHGP from non-pdHGPs (AUCs of 0.906, 0.877, and 0.805 in the training, internal validation, and external validation cohorts, respectively). The prevalence of prechemotherapy pdHGP predicted by the radiomics model was 33.0% (37/112), and the prevalence of postchemotherapy pdHGP according to the pathological analysis was 47.3% (53/112; P = 0.029). The transformation of HGP was bidirectional, with 15.2% (17/112) of CRLMs transforming from prechemotherapy pdHGP to postchemotherapy non-pdHGP and 30.4% (34/112) transforming from prechemotherapy non-pdHGP to postchemotherapy pdHGP (P = 0.005). CT-based radiomics method can be used to effectively predict the HGP transformation in chemotherapy-treated CRLM patients, thereby providing a basis for treatment decisions.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Radiómica , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos
4.
Quant Imaging Med Surg ; 13(5): 3040-3049, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37179934

RESUMEN

Background: When quantitative magnetic resonance imaging (MRI) is used to assess the activity of Graves' orbitopathy (GO), the examination is generally focused on a specific orbital tissue, especially the extraocular muscles (EOMs). However, GO usually involves the entire intraorbital soft tissue. The aim of this study was to use multiparameter MRI on multiple orbital tissues to distinguish the active and inactive GO. Methods: From May 2021 to March 2022, consecutive patients with GO were prospectively enrolled at Peking University People's Hospital (Beijing, China) and divided into those with active disease and those with inactive disease based on a clinical activity score. Patients then underwent MRI, including sequences of conventional imaging, T1 mapping, T2 mapping, and mDIXON Quant. Width, T2 signal intensity ratio (SIR), T1 values, T2 values, and fat fraction of EOMs, as well as water fraction (WF) of orbital fat (OF), were measured. Parameters were compared between the 2 groups, and a combined diagnostic model was constructed using logistic regression analysis. Receiver operating characteristic analysis was used to test the diagnostic performance of the model. Results: Sixty-eight patients with GO (27 with active GO, 41 with inactive GO) were included in the study. The active GO group had higher values of EOM thickness, T2 SIR, and T2 values, as well as higher WF of OF. The diagnostic model, which included EOM T2 value and WF of OF, demonstrated a good ability to distinguish between active and inactive GO (area under the curve, 0.878; 95% CI: 0.776-0.945; sensitivity, 88.89%; specificity, 75.61%). Conclusions: A combined model incorporating the T2 value of EOMs and the WF of OF was able to identify cases of active GO, potentially offering an effective and noninvasive method to assess pathological changes in this disease.

5.
Food Chem ; 337: 127774, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32777570

RESUMEN

Apis cerana honey collected from the Qinling Mountains in China has been widely used for its antimicrobial property in traditional Chinese medicine. However, its antibacterial mechanism against Salmonella Typhimurium LT2 is still uncertain. A total of 52 volatile components were identified using headspace-gas-chromatography-ion-mobility, and Qinling A. cerana honey exhibited more abundant aromas than monofloral honeys. The phenolic extracts of honey sample F exhibited the lowest minimum inhibitory concentration (5 mg/mL), and chlorogenic acid exhibited the highest (155.91 ± 0.79 mg/kg), followed by caffeic acid, and rutin. After being treated with the extract, cell membranes of S. Typhimurium LT2 significantly shrunk and further collapsed. The extract treatment on mice caused a significant decrease in S. Typhimurium LT2, and a dramatic increase in the potential prebiotic Lactobacillus in both the caecum and colon. The results demonstrate that the Qinling A. cerana honey extract could effectively inhibit S. Typhimurium in vitro and in vivo.


Asunto(s)
Antiinfecciosos/farmacología , Miel/análisis , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/patogenicidad , Compuestos Orgánicos Volátiles/química , Animales , Antiinfecciosos/química , Antiinfecciosos/uso terapéutico , Abejas , Modelos Animales de Enfermedad , Cromatografía de Gases y Espectrometría de Masas , Ratones , Pruebas de Sensibilidad Microbiana , Fenoles/química , Infecciones por Salmonella/tratamiento farmacológico , Compuestos Orgánicos Volátiles/farmacología , Compuestos Orgánicos Volátiles/uso terapéutico
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