Gene expression based profiling of tumor and mediastinal and hilar lymph nodes in NSCLC
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE197929 | GEO | 2022/03/05
REPOSITORIES: GEO
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Project description:Gene expression based profiling of tumor and mediastinal and hilar lymph nodes in NSCLC
| PRJNA812895 | ENA
Project description:Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely used for diagnosis and mediastinal lymph nodes staging in patients with suspicious lung cancer. Ultrasound elastography is a novel sonographical technique that can evaluate tissue compressibility. The aim of the present study was to investigate the diagnostic yield of elastography for differentiating malignant and benign mediastinal lymph nodes. Conventional EBUS B-mode features, including size, shape, border distinction, echogenicity, central hilar structure with central blood vessel and coagulation necrosis were also evaluated. The ultrasonic features were compared with the pathological results from EBUS-TBNA. 133 lymph nodes in 60 patients were assessed. Elastography displayed the highest area under the curve (AUC) (type 3 versus type 1: AUC, 0.825; 95% confidence interval [CI], 0.707-0.910) with an impressive sensitivity (100%) and an acceptable specificity (65%). The combined model covering the four positive criteria (elastography, heterogeneity, size, and shape) showed that the odds ratio for malignance is 9.44 with a 95% CI of 3.99 to 22.32 (p <0.0001). The combined model was superior to elastography alone (AUC, 0.851; sensitivity, 89.89%; specificity, 72.73%; p <0.0001). This prospective study showed that elastography is a feasible technique for classifying mediastinal lymph nodes, especially in combination with conventional EBUS imaging.
| S-EPMC5687681 | biostudies-other
Project description:Background and Objectives: Endobronchial ultrasound elastography is a new technique for describing the stiffness of tissue during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The aims of this study were to investigate the diagnostic value of Endobronchial ultrasound (EBUS) elastography for distinguishing the difference between benign and malignant lymph nodes among mediastinal and hilar lymph node. Materials and Methods: From June 2015 to August 2015, 47 patients confirmed of mediastinal and hilar lymph node enlargement through examination of Computed tomography (CT) were enrolled, and a total of 78 lymph nodes were evaluated by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). EBUS-guided elastography of lymph nodes was performed prior to EBUS-TBNA. A convex probe EBUS was used with a new EBUS processor to assess elastographic patterns that were classified based on color distribution as follows: Type 1, predominantly non-blue (green, yellow and red); Type 2, part blue, part non-blue (green, yellow and red); Type 3, predominantly blue. Pathological determination of malignant or benign lymph nodes was used as the gold standard for this study. The elastographic patterns were compared with the final pathologic results from EBUS-TBNA. Results: On pathological evaluation of the lymph nodes, 45 were benign and 33 were malignant. The lymph nodes that were classified as Type 1 on endobronchial ultrasound elastography were benign in 26/27 (96.3%) and malignant in 1/27 (3.7%); for Type 2 lymph nodes, 15/20 (75.0%) were benign and 5/20 (25.0%) were malignant; Type 3 lymph nodes were benign in 4/31 (12.9%) and malignant in 27/31 (87.1%). In classifying Type 1 as 'benign' and Type 3 as 'malignant,' the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rates were 96.43%, 86.67%, 87.10%, 96.30%, 91.38%, respectively. Conclusion: EBUS elastography of mediastinal and hilar lymph nodes is a noninvasive technique that can be performed reliably and may be helpful in the prediction of benign and malignant lymph nodes among mediastinal and hilar lymph node during EBUS-TBNA.
| S-EPMC5556648 | biostudies-other
Project description:ObjectiveEndobronchial ultrasound-guided transbronchial needle aspiration is of diagnostic value in hilar/mediastinal (N1/N2) lymph node staging. We assessed the utility of endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients with N1/N2 lymph nodes detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography.MethodsFifty lung cancer patients with N1/N2 disease on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography underwent endobronchial ultrasound-guided transbronchial needle aspiration for pathological lymph nodes between November 2012 and April 2015. The diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration, lymph node site and size, number of needle passes and complications were evaluated retrospectively from patients' medical records. Malignancy was defined as a maximum standardized uptake value (SUVmax) >2.5.ResultsThe median longest diameter of the 61 lymph nodes (29 subcarinal, 21 right lower paratracheal, 6 left lower paratracheal, 4 right hilar and 1 upper paratracheal) was 23.4 mm (range: 10.4-45.7); the median number of needle passes was 2 (range: 1-5). There were no severe complications. A definitive diagnosis was made by endobronchial ultrasound-guided transbronchial needle aspiration in 39 patients (31 adenocarcinomas, 3 small-cell carcinomas, 2 squamous-cell carcinomas, 3 large-cell neuroendocrine carcinomas). In the remaining 11 patients, the diagnosis was indefinite: insufficient endobronchial ultrasound-guided transbronchial needle aspiration material was collected in two patients and non-specific lymphadenopathy was confirmed by endobronchial ultrasound-guided transbronchial needle aspiration or thoracotomy in the other nine patients. The mean lymph node SUVmax was 7.09 (range: 2.90-26.9) and was significantly higher in true-positive than in false-positive nodes (P < 0.05, t-test). Non-specific lymphadenopathy was diagnosed by expert visual interpretation of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography images in five of the nine patients.ConclusionEndobronchial ultrasound-guided transbronchial needle aspiration accurately diagnoses N1/N2 disease detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography.
| S-EPMC4930148 | biostudies-literature
Project description:BACKGROUND:We aimed to develop radiomic models based on different phases of computed tomography (CT) imaging and to investigate the efficacy of models for diagnosing mediastinal metastatic lymph nodes (LNs) in non-small cell lung cancer (NSCLC). METHODS:Eighty-six NSCLC patients were enrolled in this study, and we selected 231 mediastinal LNs confirmed by pathology results as the subjects which were divided into training (n?=?163) and validation cohorts (n?=?68). The regions of interest (ROIs) were delineated on CT scans in the plain phase, arterial phase and venous phase, respectively. Radiomic features were extracted from the CT images in each phase. A least absolute shrinkage and selection operator (LASSO) algorithm was used to select features, and multivariate logistic regression analysis was used to build models. We constructed six models (orders 1-6) based on the radiomic features of the single- and dual-phase CT images. The performance of the radiomic model was evaluated by the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV). RESULTS:A total of 846 features were extracted from each ROI, and 10, 9, 5, 2, 2, and 9 features were chosen to develop models 1-6, respectively. All of the models showed excellent discrimination, with AUCs greater than 0.8. The plain CT radiomic model, model 1, yielded the highest AUC, specificity, accuracy and PPV, which were 0.926 and 0.925; 0.860 and 0.769; 0.871 and 0.882; and 0.906 and 0.870 in the training and validation sets, respectively. When the plain and venous phase CT radiomic features were combined with the arterial phase CT images, the sensitivity increased from 0.879 and 0.919 to 0.949 and 0979 and the NPV increased from 0.821 and 0.789 to 0.878 and 0.900 in the training group, respectively. CONCLUSIONS:All of the CT radiomic models based on different phases all showed high accuracy and precision for the diagnosis of LN metastasis (LNM) in NSCLC patients. When combined with arterial phase CT, the sensitivity and NPV of the model was be further improved.
| S-EPMC7003415 | biostudies-literature
Project description:Individualized outcome prediction classifiers were successfully constructed through expression profiling of a total of 8,644 genes in 50 non-small cell lung cancer (NSCLC) cases, which had been consecutively operated on within a defined short period of ti
2023-10-02 | GSE244158 | GEO
Project description:PURPOSE: Non-small cell lung cancers (NSCLC) comprise multiple distinct biological groups with different prognoses. For example, patients with epithelial-like (EL) tumors have a better prognosis and exhibit greater sensitivity to inhibitors of the epidermal growth factor receptor (EGFR) pathway than patients with mesenchymal-like (ML) tumors. Here we test the hypothesis that EL NSCLCs can be distinguished from ML NSCLCs on the basis of global DNA methylation patterns. EXPERIMENTAL DESIGN: To determine whether phenotypic subsets of NSCLC can be defined based on their DNA methylation patterns, we combined microfluidics-based gene expression analysis and genome-wide methylation profiling. We derived robust classifiers for both gene expression and methylation in cell lines and tested these classifiers in surgically resected NSCLC tumors. We validate our approach using quantitative RT-PCR and methylation specific PCR in formalin-fixed biopsies from NSCLC patients who went on to fail front-line chemotherapy. RESULTS: We show that patterns of methylation divide NSCLCs into EL and ML subsets as defined by gene expression and that these signatures are similarly correlated in NSCLC cell lines and tumors. We identify multiple DMRs, including ERBB2 and ZEB2, whose methylation status is strongly associated with an epithelial phenotype in NSCLC cell lines, surgically resected tumors, and formalin-fixed biopsies from NSCLC patients who went on to fail front-line chemotherapy. CONCLUSIONS: Our data demonstrate that patterns of DNA methylation can divide NSCLCs into two phenotypically distinct subtypes of tumors and provide proof of principle that differences in DNA methylation can be used for predictive biomarker discovery and development. To determine whether phenotypic subsets of NSCLC can be defined based on their DNA methylation patterns, we combined microfluidics-based gene expression analysis and genome-wide methylation profiling. We derived robust classifiers for both gene expression and methylation in cell lines and tested these classifiers in surgically resected NSCLC tumors. We validate our approach using quantitative RT-PCR and methylation specific PCR in formalin-fixed biopsies from NSCLC patients who went on to fail front-line chemotherapy.
2012-03-03 | E-GEOD-36216 | biostudies-arrayexpress
Project description:Non–small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide due to late diagnosis and lack of effective therapies to treat metastatic disease. About one third of NSCLC patients present at diagnosis with locally advanced cancer (stage IIIA) which metastasizes ipsilateral mediastinal or subcarinal lymph nodes (N2). Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for resectable N2 disease. However, the majority of patients do not respond to NACT and show persistent lymph nodal metastases and an adverse outcome. Our scant knowledge of the molecular biology of lymph node metastases (LNmets) represents a major obstacle to develop more effective therapies. Here, we investigated gene expression profile (coding and non-coding) of LNmets collected by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and mediastinoscopy, in two cohorts of stage IIIA patients before NACT (N=70). We discovered a microRNA expression signature in LNmets predictive of NACT response of N2 patients. Importantly, we unveiled a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance and impact T cell viability in NSCLC. Our data suggests the relevance of LNmets molecular profiling to predict response to NACT likewise presents strong evidences of a miRNA-based mechanism which functionally links chemotherapy response with PD-L1 regulation.
2022-12-31 | GSE193707 | GEO
Project description:AimsThis study evaluated the safety and efficacy of stereotactic radiation therapy (SRT) for the treatment of patients with oligometastases or oligorecurrence within mediastinal lymph nodes (MLNs) originating from different tumors.MethodsBetween October 2006 and May 2015, patients with MLN oligometastases or oligorecurrence were enrolled and treated with SRT at our hospital. The primary endpoint was MLN local control (LC). Secondary endpoints were time to symptom alleviation, overall survival (OS) after SRT, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0).ResultsEighty-five patients with 98 MLN oligometastases or oligorecurrences were treated with SRT. For the entire cohort, the 1-year and 5-year actuarial LC rates were 97% and 77%, respectively. Of 53 symptomatic patients, symptom alleviation was observed in 47 (89%) after a median of 5 days (range, 3-30 days). The median OS was 27.2 months for all patients. For patients with non-small cell lung cancer, univariate and multivariate analyses revealed that a shorter interval between diagnosis of primary tumors and SRT and larger MLN SRT volume were associated with worse OS. CTCAE v4.0 ? Grade 3 toxicities occurred in six patients (7%), with Grade 5 in three patients (all with RT history to MLN station 7).ConclusionsSRT is a safe and efficacious treatment modality for patients with oligometastases or oligorecurrence to MLNs originating from different tumors, except for patients who received radiotherapy to MLN station 7. Further investigation is warranted to identify the patients who benefit most from this treatment modality.
| S-EPMC4951277 | biostudies-literature
Project description:BackgroundAccurate evaluation of lymph node (LN) status is critical for determining the treatment options in patients with non-small cell lung cancer (NSCLC). This study aimed to develop and validate a 18F-FDG PET-based radiomic model for the identification of metastatic LNs from the hypermetabolic mediastinal-hilar LNs in NSCLC.MethodsWe retrospectively reviewed 259 patients with hypermetabolic LNs who underwent pretreatment 18F-FDG PET/CT and were pathologically confirmed as NSCLC from two centers. Two hundred twenty-eight LNs were allocated to a training cohort (LN = 159) and an internal validation cohort (LN = 69) from one center (7:3 ratio), and 60 LNs were enrolled to an external validation cohort from the other. Radiomic features were extracted from LNs of PET images. A PET radiomics signature was constructed by multivariable logistic regression after using the least absolute shrinkage and selection operator (LASSO) method with 10-fold cross-validation. The PET radiomics signature (model 1) and independent predictors from CT image features and clinical data (model 2) were incorporated into a combined model (model 3). A nomogram was plotted for the complex model, and the performance of the nomogram was assessed by its discrimination, calibration, and clinical usefulness.ResultsThe area under the curve (AUC) values of model 1 were 0.820, 0.785, and 0.808 in the training, internal, and external validation cohorts, respectively, showing good diagnostic efficacy for lymph node metastasis (LNM). Furthermore, model 2 was able to discriminate metastatic LNs in the training (AUC 0.780), internal (AUC 0.794), and external validation cohorts (AUC 0.802), respectively. Model 3 showed optimal diagnostic performance among the three cohorts, with an AUC of 0.874, 0.845, and 0.841, respectively. The nomogram based on the model 3 showed good discrimination and calibration.ConclusionsOur study revealed that PET radiomics signature, especially when integrated with CT imaging features, showed the ability to identify true and false positives of mediastinal-hilar LNM detected by PET/CT in patients with NSCLC, which would help clinicians to make individual treatment decisions.
| S-EPMC8457532 | biostudies-literature