RESUMO
BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.
Assuntos
Radiômica , Neoplasias Gástricas , Humanos , Estudos de Coortes , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Estudos Retrospectivos , Instabilidade de Microssatélites , Imunoterapia , Tomografia Computadorizada por Raios X , ImunoglobulinasRESUMO
OBJECTIVES: To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS: The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS: A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS: The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT: A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS: ⢠The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. ⢠Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. ⢠The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.
Assuntos
Neoplasias dos Ductos Biliares , Tumor de Klatskin , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Linfática/patologia , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/cirurgia , Radiômica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Linfonodos/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologiaRESUMO
OBJECTIVES: Genus Clostridium sensu stricto is generally regarded as the true Clostridium genus, which includes important human and animal pathogens and industrially relevant microorganisms. Besides, it is also a prominent member of plant-associated endophytes. However, our knowledge of endophytic Clostridium is limited. METHODS: In this study, the endophytes were isolated under anaerobic condition from the roots of Paris polyphylla Smith var. yunnanensis. Subsequently, a polyphasic taxonomic approach was used to clarify their taxonomic positions. The fermentation products were measured in the isolates with HPLC analysis. Comparative genomics was performed on these new strains and other relatives. RESULTS: In total, nine endophytic strains belonging to the genus Clostridium sensu stricto were isolated, and three of them were identified as new species. Seven of nine strains could produce acetate, propionate, and butyrate. Only two strains could produce ethanol, although genomics analysis suggested that only two of them were without genes for solventogenesis. Different from the endophytic strains, the phylogenetically closely related non-endophytic strains showed significant enrichment effects on some metabolic pathways involving environmental information processing, carbohydrate, and amino acid metabolisms, etc. It suggests that the genomes of these endophytic strains had undergone subtle changes associated with environmental adaptations. CONCLUSION: Consequently, strains YIM B02505T, YIM B02515T, and YIM B02565T are proposed to represent a new species of the genus Clostridium sensu stricto, for which the names Clostridium yunnanense sp. nov., Clostridium rhizosphaerae sp. nov., and Clostridium paridis sp. nov. are suggested.
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Endófitos , Ácidos Graxos , Humanos , Endófitos/genética , Ácido Acético , Etanol , Análise de Sequência de DNA , Composição de Bases , Clostridium/genética , RNA Ribossômico 16S/genética , Genômica , Filogenia , DNA Bacteriano/genética , Técnicas de Tipagem BacterianaRESUMO
A novel endophytic strain, designated YIM B02564T, was isolated from the root of Paris polyphylla Smith var. yunnanensis obtained from Yunnan Province, southwest China. By using a polyphasic approach, cells of the strain were characterized as facultative anaerobic, Gram-positive and rod-shaped. The growth conditions of the strain were found to occur at 20-55 °C (optimum, 30 °C), pH 6.0-9.0 (optimum, pH 7.0). Strain YIM B02564T can tolerate 2% NaCl concentration. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain YIM B02564T belonged to the genus Neobacillus and the 16S rRNA gene sequence similarity values of strain YIM B02564T to the type strains of members of this genus ranged from 95.6 to 97.8%. The DNA G+C content of strain YIM B02564T calculated from the whole genome sequence was 41.6 mol%. Values of the ANI and the dDDH between strain YIM B02564T and its closely related Neobacillus species were below 77.9% and 21.5%. Strain YIM B02564T contained MK-7 as the major menaquinone, iso-C15:0 and anteiso-C15:0 as the major fatty acids. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified aminophospholipid and four unidentified lipids. It contained meso-diaminopimelic acid in the cell-wall peptidoglycan. On the basis of polyphasic analysis, strain YIM B02564T could be differentiated genotypically and phenotypically from recognized species of the genus Neobacillus. The isolate therefore represents a novel species, for which the name Neobacillus paridis is proposed. The type strain is YIM B02564T (= JCM 34668T = CGMCC 1.18655T).
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Endófitos , Liliaceae , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Endófitos/genética , Ácidos Graxos/análise , Hibridização de Ácido Nucleico , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
A Gram-negative, facultative anaerobic bacterial strain, designated YIM B02556T, was isolated from the root of Paris polyphylla Smith var. yunnanensis collected from Yunnan Province, southwest China. By using a polyphasic approach, its taxonomic position was investigated. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain YIM B02556T belonged to the genus Azospirillum and the 16S rRNA gene sequence similarity values of strain YIM B02556T to the type strains of members of this genus ranged from 94.9 to 98.3%. Overall genome relatedness index (OGRI) analysis estimated based on average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) between YIM B02556T and other Azospirillum species type strains were <90.8% and <37.8%, lower than the limit of species circumscription. Cells of the strain were characterized as oxidase- and catalase-positive, with motility provided by flagella. The growth conditions of the strain were found to occur at 20-40 °C (optimum, 35 °C), and pH 6.0-9.5 (optimum, pH 7.5). Strain YIM B02556T can tolerate 2% NaCl concentration. Strain YIM B02556T contained Q-10 as the major ubiquinone. The major fatty acids were C18:1 ω7c and summed feature three (C16:1 ω7c and/or C16:1 ω6c). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. Based on polyphasic analysis, strain YIM B02556T could be differentiated genotypically and phenotypically from recognized species of the genus Azospirillum. Therefore, the isolate represents a novel species, for which the name Azospirillum endophyticum is proposed. The type strain is YIM B02556T (=JCM 34631T=CGMCC 1.18654T).
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Azospirillum , RNA Ribossômico 16S/genética , Azospirillum/genética , Filogenia , Endófitos/genética , Composição de Bases , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Fosfolipídeos/análise , China , Ácidos Graxos/análiseRESUMO
Culture-dependent and metagenomic binning techniques were employed to gain an insight into the diversification of gut bacteria in Rhinopithecius bieti, a highly endangered primate endemic to China. Our analyses revealed that Bacillota_A and Bacteroidota were the dominant phyla. These two phyla species are rich in carbohydrate active enzymes, which could provide nutrients and energy for their own or hosts' survival under different circumstances. Among the culturable bacteria, one novel bacterium, designated as WQ 2009T, formed a distinct branch that had a low similarity to the known species in the family Sphingobacteriaceae, based on the phylogenetic analysis of its 16S rRNA gene sequence or phylogenomic analysis. The ANI, dDDH and AAI values between WQ 2009T and its most closely related strains S. kitahiroshimense 10CT, S. pakistanense NCCP-246T and S. faecium DSM 11690T were significantly lower than the accepted cut-off values for microbial species delineation. All results demonstrated that WQ 2009T represent a novel genus, for which names Rhinopithecimicrobium gen. nov. and Rhinopithecimicrobium faecis sp. nov. (Type strain WQ 2009T = CCTCC AA 2021153T = KCTC 82941T) are proposed.
Assuntos
Microbioma Gastrointestinal , Metagenômica , Filogenia , RNA Ribossômico 16S , Animais , Microbioma Gastrointestinal/genética , Metagenômica/métodos , RNA Ribossômico 16S/genética , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Bacteroidetes/classificaçãoRESUMO
RATIONALE AND OBJECTIVES: To develop and validate a nomogram for the prediction of stent dysfunction after transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with hepatitis B cirrhosis. MATERIALS AND METHODS: From 2012 to 2020, 355 patients with hepatitis B cirrhosis who underwent TIPS placements were enrolled in this study. A multivariable logistic regression analysis was applied to determine independent risk factors for the nomogram construction. Discrimination, calibration, and clinical usefulness of the prediction model were assessed by using receiver operating characteristic curves, calibration scatter plots, and a decision curve analysis (DCA). RESULTS: Independent factors for TIPS stent dysfunction included diabetes, previous splenectomy, the shunting branch of the portal vein, and stent position, which were used to construct the nomogram. The AUC values in the training and validation cohorts were 0.817 (95% CI: 0.731-0.903) and 0.804 (95% CI: 0.673-0.935), respectively, which suggested a good predictive ability. The calibration curves in both cohorts revealed good agreement between the predictions and actual observations. The DCA curve indicated that when the threshold probability ranged from 2% to 88%, the nomogram could provide clinical usefulness and a net benefit. CONCLUSION: The nomogram that we developed could be conveniently used to predict TIPS stent dysfunction in patients with hepatitis B cirrhosis.
Assuntos
Hepatite B , Nomogramas , Humanos , Cirrose Hepática/cirurgia , Veia Porta , Estudos Retrospectivos , StentsRESUMO
Purpose: The study aimed to construct and evaluate a CT-Based radiomics model for noninvasive detecting perineural invasion (PNI) of perihilar cholangiocarcinoma (pCCA) preoperatively. Materials and Methods: From February 2012 to October 2021, a total of 161 patients with pCCA who underwent resection were retrospectively enrolled in this study. Patients were allocated into the training cohort and the validation cohort according to the diagnostic time. Venous phase images of contrast-enhanced CT were used for radiomics analysis. The intraclass correlation efficient (ICC), the correlation analysis, and the least absolute shrinkage and selection operator (LASSO) regression were applied to select radiomics features and built radiomics signature. Logistic regression analyses were performed to establish a clinical model, a radiomics model, and a combined model. The performance of the predictive models was measured by area under the receiver operating characteristic curve (AUC), and pairwise ROC comparisons between models were tested using the Delong method. Finally, the model with the best performance was presented as a nomogram, and its calibration and clinical usefulness were assessed. Results: Finally, 15 radiomics features were selected to build a radiomics signature, and three models were developed through logistic regression. In the training cohort, the combined model showed a higher predictive capability (AUC = 0.950) than the radiomics model and the clinical model (AUC: radiomics = 0.914, clinical = 0.756). However, in the validation cohort, the AUC of the radiomics model (AUC = 0.885) was significantly higher than the other two models (AUC: combined = 0.791, clinical = 0.567). After comprehensive consideration, the radiomics model was chosen to develop the nomogram. The calibration curve and decision curve analysis (DCA) suggested that the nomogram had a good consistency and clinical utility. Conclusion: We developed a CT-based radiomics model with good performance to noninvasively predict PNI of pCCA preoperatively.