RÉSUMÉ
Non-small cell lung cancer (NSCLC) is the most prevalent histological type of lung cancer and the leading cause of death globally. Patients with NSCLC have a poor prognosis for various factors, and a late diagnosis is one of them. The DNA methylation of CpG island sequences found in the promoter regions of tumor suppressor genes has recently received attention as a potential biomarker of human cancer. In this study, we report DNA methylation changes of the adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1), which belongs to the ATP cassette transporter family in NSCLC patients. Our results demonstrate that ABCG1 is hyper-methylation in NSCLC samples, and these changes are negatively correlated to gene and protein expression. Furthermore, the expression of the ABCG1 gene is significantly associated with the survival time of lung adenocarcinoma (LUAD) patients; however, it did not show a correlation to overall survival (OS) of lung squamous cell carcinoma (LUSC) patients. Notably, we found ABCG1 methylation status at locus cg20214535 is strongly associated with the survival time and consistently observed hyper-methylation in LUAD samples. This novel finding suggests ABCG1 is a potential candidate for targeted therapy in lung cancer via this specific probe. In addition, we illustrate the protein-protein interaction (PPI) of ABCG1 with other proteins and the strong communication of ABCG1 with immune cells.
Sujet(s)
Adénocarcinome pulmonaire , Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Humains , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/anatomopathologie , Adénocarcinome pulmonaire/génétique , Adénocarcinome pulmonaire/anatomopathologie , Méthylation de l'ADN , Épigenèse génétique , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP/génétique , Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP/métabolismeRÉSUMÉ
Lung adenocarcinoma (LUAD) is the most prevalent lung cancer and one of the leading causes of death. Previous research found a link between LUAD and Aldehyde Dehydrogenase 2 (ALDH2), a member of aldehyde dehydrogenase gene (ALDH) superfamily. In this study, we identified additional useful prognostic markers for early LUAD identification and targeting LUAD therapy by analyzing the expression level, epigenetic mechanism, and signaling activities of ALDH2 in LUAD patients. The obtained results demonstrated that ALDH2 gene and protein expression significantly downregulated in LUAD patient samples. Furthermore, The American Joint Committee on Cancer (AJCC) reported that diminished ALDH2 expression was closely linked to worse overall survival (OS) in different stages of LUAD. Considerably, ALDH2 showed aberrant DNA methylation status in LUAD cancer. ALDH2 was found to be downregulated in the proteomic expression profile of several cell biology signaling pathways, particularly stem cell-related pathways. Finally, the relationship of ALDH2 activity with stem cell-related factors and immune system were reported. In conclusion, the downregulation of ALDH2, abnormal DNA methylation, and the consequent deficit of stemness signaling pathways are relevant prognostic and therapeutic markers in LUAD.
RÉSUMÉ
O6-Methylguanine-DNA-methyltransferase (MGMT) promoter methylation was shown in many studies to be an important predictive biomarker for temozolomide (TMZ) resistance and poor progression-free survival in glioblastoma multiforme (GBM) patients. However, identifying the MGMT methylation status using molecular techniques remains challenging due to technical limitations, such as the inability to obtain tumor specimens, high prices for detection, and the high complexity of intralesional heterogeneity. To overcome these difficulties, we aimed to test the feasibility of using a novel radiomics-based machine learning (ML) model to preoperatively and noninvasively predict the MGMT methylation status. In this study, radiomics features extracted from multimodal images of GBM patients with annotated MGMT methylation status were downloaded from The Cancer Imaging Archive (TCIA) public database for retrospective analysis. The radiomics features extracted from multimodal images from magnetic resonance imaging (MRI) had undergone a two-stage feature selection method, including an eXtreme Gradient Boosting (XGBoost) feature selection model followed by a genetic algorithm (GA)-based wrapper model for extracting the most meaningful radiomics features for predictive purposes. The cross-validation results suggested that the GA-based wrapper model achieved the high performance with a sensitivity of 0.894, specificity of 0.966, and accuracy of 0.925 for predicting the MGMT methylation status in GBM. Application of the extracted GBM radiomics features on a low-grade glioma (LGG) dataset also achieved a sensitivity 0.780, specificity 0.620, and accuracy 0.750, indicating the potential of the selected radiomics features to be applied more widely on both low- and high-grade gliomas. The performance indicated that our model may potentially confer significant improvements in prognosis and treatment responses in GBM patients.
Sujet(s)
Tumeurs du cerveau , Glioblastome , Gliome , Tumeurs du cerveau/imagerie diagnostique , Tumeurs du cerveau/génétique , Tumeurs du cerveau/anatomopathologie , Méthylation de l'ADN , DNA modification methylases/génétique , DNA modification methylases/métabolisme , Enzymes de réparation de l'ADN/génétique , Enzymes de réparation de l'ADN/métabolisme , Glioblastome/imagerie diagnostique , Glioblastome/génétique , Gliome/génétique , Humains , Apprentissage machine , O(6)-methylguanine-DNA methyltransferase/génétique , Études rétrospectives , Protéines suppresseurs de tumeurs/génétiqueRÉSUMÉ
Glioma is a Center Nervous System (CNS) neoplasm that arises from the glial cells. In a new scheme category of the World Health Organization 2016, lower-grade gliomas (LGGs) are grade II and III gliomas. Following the discovery of suppression of negative immune regulation, immunotherapy is a promising effective treatment method for lower-grade glioma patients. However, the therapy is not effective for all types of LGGs, and tumor mutational burden (TMB) has been shown to be a potential biomarker for the susceptibility and prognosis of immunotherapy in lower-grade glioma patients. Hence, predicting TMB benefits brain cancer patients. In this study, we investigated the correlation between MRI (magnetic resonance imaging)-based radiomic features and TMB in LGG by applying machine learning methods. Six machine learning classifiers were examined on the features extracted from the genetic algorithm. Subsequently, a light gradient boosting machine (LightGBM) succeeded in selecting 11 radiomics signatures for TMB classification. Our LightGBM model resulted in high accuracy of 0.7936, and reached a balance between sensitivity and specificity, achieving 0.76 and 0.8107, respectively. To our knowledge, our study represents the best model for classification of TMB in LGG patients at present.
RÉSUMÉ
In 2016, the World Health Organization (WHO) updated the glioma classification by incorporating molecular biology parameters, including low-grade glioma (LGG). In the new scheme, LGGs have three molecular subtypes: isocitrate dehydrogenase (IDH)-mutated 1p/19q-codeleted, IDH-mutated 1p/19q-noncodeleted, and IDH-wild type 1p/19q-noncodeleted entities. This work proposes a model prediction of LGG molecular subtypes using magnetic resonance imaging (MRI). MR images were segmented and converted into radiomics features, thereby providing predictive information about the brain tumor classification. With 726 raw features obtained from the feature extraction procedure, we developed a hybrid machine learning-based radiomics by incorporating a genetic algorithm and eXtreme Gradient Boosting (XGBoost) classifier, to ascertain 12 optimal features for tumor classification. To resolve imbalanced data, the synthetic minority oversampling technique (SMOTE) was applied in our study. The XGBoost algorithm outperformed the other algorithms on the training dataset by an accuracy value of 0.885. We continued evaluating the XGBoost model, then achieved an overall accuracy of 0.6905 for the three-subtype classification of LGGs on an external validation dataset. Our model is among just a few to have resolved the three-subtype LGG classification challenge with high accuracy compared with previous studies performing similar work.
Sujet(s)
Tumeurs du cerveau , Gliome , Tumeurs du cerveau/imagerie diagnostique , Tumeurs du cerveau/anatomopathologie , Gliome/anatomopathologie , Humains , Isocitrate dehydrogenases/génétique , Apprentissage machine , Imagerie par résonance magnétique/méthodes , Mutation/génétique , Études rétrospectivesRÉSUMÉ
PURPOSE: Cranial magnetic resonance imaging (MRI) is recommended to identify intracranial lesions in girls with central precocious puberty (CPP). Yet, the use of routine MRI scans in girls with CPP is still debatable, as pathological findings in girls 6 years of age or older with CPP are limited. Therefore, we aimed to identify the prevalence of brain lessons in CPP patients stratified by age group (0-2, 2-6, and 6-8 years). METHODS: This retrospective cross-sectional study recruited 257 girls diagnosed with CPP for 6 years (2010-2016). MRI was used to detect brain abnormalities. Levels of luteinizing hormone, follicle-stimulating hormone, and sex hormones in blood samples were measured. RESULTS: Most girls had no brain lesions (82.9%, n=213), and of the minor proportion of girls with CPP that exhibited brain lesions (17.1%, n=44), 32 girls had organic CPP. Pathological findings were detected in 33.3% (2 of 6) of girls aged 0-2 years, 15.6% (5 of 32) of girls aged 2-6 years, and 3.6% (8 of 219) of girls aged 6-8 years. Hypothalamic hamartoma and tumors in the pituitary stalk were the most common pathological findings. The likelihood of brain lesions decreased with age. Girls with organic CPP were more likely to be younger (6.1±2.4 vs. 7.3±1.3 years, p<0.01) than girls with idiopathic CPP. CONCLUSION: Older girls appeared to have a lower prevalence of organic CPP. Clinicians should cautiously use cranial MRI for girls aged 6-8 years with CPP.
RÉSUMÉ
BACKGROUND: In the field of glioma, transcriptome subtypes have been considered as an important diagnostic and prognostic biomarker that may help improve the treatment efficacy. However, existing identification methods of transcriptome subtypes are limited due to the relatively long detection period, the unattainability of tumor specimens via biopsy or surgery, and the fleeting nature of intralesional heterogeneity. In search of a superior model over previous ones, this study evaluated the efficiency of eXtreme Gradient Boosting (XGBoost)-based radiomics model to classify transcriptome subtypes in glioblastoma patients. METHODS: This retrospective study retrieved patients from TCGA-GBM and IvyGAP cohorts with pathologically diagnosed glioblastoma, and separated them into different transcriptome subtypes groups. GBM patients were then segmented into three different regions of MRI: enhancement of the tumor core (ET), non-enhancing portion of the tumor core (NET), and peritumoral edema (ED). We subsequently used handcrafted radiomics features (n = 704) from multimodality MRI and two-level feature selection techniques (Spearman correlation and F-score tests) in order to find the features that could be relevant. RESULTS: After the feature selection approach, we identified 13 radiomics features that were the most meaningful ones that can be used to reach the optimal results. With these features, our XGBoost model reached the predictive accuracies of 70.9%, 73.3%, 88.4%, and 88.4% for classical, mesenchymal, neural, and proneural subtypes, respectively. Our model performance has been improved in comparison with the other models as well as previous works on the same dataset. CONCLUSION: The use of XGBoost and two-level feature selection analysis (Spearman correlation and F-score) could be expected as a potential combination for classifying transcriptome subtypes with high performance and might raise public attention for further research on radiomics-based GBM models.
Sujet(s)
Tumeurs du cerveau , Glioblastome , Humains , Apprentissage machine , Imagerie par résonance magnétique , Études rétrospectives , TranscriptomeRÉSUMÉ
Essential genes contain key information of genomes that could be the key to a comprehensive understanding of life and evolution. Because of their importance, studies of essential genes have been considered a crucial problem in computational biology. Computational methods for identifying essential genes have become increasingly popular to reduce the cost and time-consumption of traditional experiments. A few models have addressed this problem, but performance is still not satisfactory because of high dimensional features and the use of traditional machine learning algorithms. Thus, there is a need to create a novel model to improve the predictive performance of this problem from DNA sequence features. This study took advantage of a natural language processing (NLP) model in learning biological sequences by treating them as natural language words. To learn the NLP features, a supervised learning model was consequentially employed by an ensemble deep neural network. Our proposed method could identify essential genes with sensitivity, specificity, accuracy, Matthews correlation coefficient (MCC), and area under the receiver operating characteristic curve (AUC) values of 60.2%, 84.6%, 76.3%, 0.449, and 0.814, respectively. The overall performance outperformed the single models without ensemble, as well as the state-of-the-art predictors on the same benchmark dataset. This indicated the effectiveness of the proposed method in determining essential genes, in particular, and other sequencing problems, in general.