CpG Methylation Signature Predicts Recurrence in Early-Stage Hepatocellular Carcinoma: Results From a Multicenter Study

2017 ◽  
Vol 35 (7) ◽  
pp. 734-742 ◽  
Author(s):  
Jiliang Qiu ◽  
Baogang Peng ◽  
Yunqiang Tang ◽  
Yeben Qian ◽  
Pi Guo ◽  
...  

Purpose Early-stage hepatocellular carcinoma (E-HCC) is being diagnosed increasingly, and in one half of diagnosed patients, recurrence will develop. Thus, it is urgent to identify recurrence-related markers. We investigated the effectiveness of CpG methylation in predicting recurrence for patients with E-HCCs. Patients and Methods In total, 576 patients with E-HCC from four independent centers were sorted by three phases. In the discovery phase, 66 tumor samples were analyzed using the Illumina Methylation 450k Beadchip. Two algorithms, Least Absolute Shrinkage and Selector Operation and Support Vector Machine-Recursive Feature Elimination, were used to select significant CpGs. In the training phase, penalized Cox regression was used to further narrow CpGs into 140 samples. In the validation phase, candidate CpGs were validated using an internal cohort (n = 141) and two external cohorts (n = 191 and n =104). Results After combining the 46 CpGs selected by the Least Absolute Shrinkage and Selector Operation and the Support Vector Machine-Recursive Feature Elimination algorithms, three CpGs corresponding to SCAN domain containing 3, Src homology 3-domain growth factor receptor-bound 2-like interacting protein 1, and peptidase inhibitor 3 were highlighted as candidate predictors in the training phase. On the basis of the three CpGs, a methylation signature for E-HCC (MSEH) was developed to classify patients into high- and low-risk recurrence groups in the training cohort ( P < .001). The performance of MSEH was validated in the internal cohort ( P < .001) and in the two external cohorts ( P < .001; P = .002). Furthermore, a nomogram comprising MSEH, tumor differentiation, cirrhosis, hepatitis B virus surface antigen, and antivirus therapy was generated to predict the 5-year recurrence-free survival in the training cohort, and it performed well in the three validation cohorts (concordance index: 0.725, 0.697, and 0.693, respectively). Conclusion MSEH, a three-CpG–based signature, is useful in predicting recurrence for patients with E-HCC.

2021 ◽  
Author(s):  
Rongrong Bian ◽  
Guorong Zhu ◽  
Feng Zhao ◽  
Rui Chen ◽  
Wengji Xia ◽  
...  

Abstract Background: Early-stage non-small cell lung cancer (NSCLC) is being diagnosed increasingly, and in 30% of diagnosed patients, recurrence will develop within 5 years. Thus, it is urgent to identify recurrence-related markers in order to optimize the management of patient-tailored therapeutics. The aim of the study was to develop a feasible tool to optimize the recurrence prediction of stage I NSCLC. Methods: The eligible datasets were downloaded from TCGA and GEO. In discovery phase, two algorithms, Least Absolute Shrinkage and Selector Operation and Support Vector Machine-Recursive Feature Elimination, were used to identify candidate genes. Recurrence associated signature was developed by penalized cox regression. The nomogram was constructed and further tested via two independent cohorts. Results: In this retrospective study, 14 eligible datasets and 7 published signatures were included. In discovery phase, 42 significant genes were highlighted as candidate predictors by two algorithms. A 13-gene based signature was generated by penalized cox regression categorized training cohort into high-risk and low-risk subgroups (HR = 8.873, 95% CI:4.228–18.480 P < 0.001). Furthermore, a nomogram integrating the recurrence related signature, age, and histology was developed to predict the recurrence-free survival in the training cohort, which performed well in the two external validation cohorts (concordance index: 0.737, 95%CI:0.732–0.742, P < 0.001; 0.666, 95%CI: 0.650–0.682, P < 0.001; 0.651, 95%CI:0.637–0.665, P < 0.001 respectively). Conclusions: The proposed nomogram is a promising tool for estimating recurrence free survival in stage I NSCLC, which might have tremendous value in guiding adjuvant therapy. Prospective studies are needed to test the clinical utility of the nomogram in individualized management of stage I NSCLC.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21044-e21044
Author(s):  
Luyu Huang ◽  
Haiyu Zhou ◽  
Herui Yao ◽  
Yunfang Yu ◽  
Hongyuan Zhu ◽  
...  

e21044 Background: The purpose of this study was to investigate whether the combined radiomic model based on tumor-associated and margin-related (5mm) radiomic features can effectively improve prediction performance of distinguishing precancerous lesions from early stage lung adenocarcinoma. Methods: 264 patients underwent preoperative chest CT in Guangdong Provincial People’s hospital from March 1, 2015 to December 31,2019 were sorted by three cohorts. All lesions were pathologically confirmed as precancerous lesions or Stage I lung adenocarcinoma and a total of 861 analyzable radiomic features were extracted from two segmented lesions including pulmonary lesions and margins, using PyRadiomics by two senior radiologists. In training cohort, 145 patients (70%) are selected randomly from the single-nodular patients (N = 207). As for the validation cohorts, the models were validated using the resting 62 patients from single-nodular cohort and multi-nodular cohort (n = 57) respectively. Least Absolute Shrinkage and Selector Operation and Support Vector Machine-Recursive Feature Elimination were used for feature selection. ROC analysis and AUC were used to evaluate the performance of three models which were developed by multiple logistic regression on distinguishing the precancerous lesions from early stage lung adenocarcinoma. Results: Selected features from pulmonary lesions and pericarcinous tissue were developed into two independent radiomic models and a combined model. Margin-related radiomic model performs well in three validation cohorts. The AUC Brock of single-nodular cohort in training cohort was 0.912 (95% CI: 0.876-0.948), while in single-nodular validation cohort was 0.93 (95% CI: 0.862-0.966). Multi-nodular validation cohort in this model shows an AUC of 0.891 (95% CI = 0.824–0.943). Comparing combined model and tumor-associated radiomic model, it is found that the AUC of combined model was improved from 0.865 (95% CI: 0.767-0.963) to 0.94 (95% CI: 0.767-0.963) for single-nodular validation cohort. Respectively, this combined model also performs well in multi-nodular validation cohort. Conclusions: This study demonstrated the potential of margin-related radiomic features based on preoperative CT scans to distinguish precancerous lesions from early stage lung adenocarcinoma. The constructed radiomic model provided an easy-to-use, preoperative tool for surgeons to develop accurate therapeutic strategies for multi-nodular patients.


2021 ◽  
pp. 1-10
Author(s):  
Shuai He ◽  
Jin-Feng Li ◽  
Hao Tian ◽  
Ye Sang ◽  
Xiao-Jing Yang ◽  
...  

BACKGROUND: Early recurrence is the main obstacle for long-term survival of hepatocellular carcinoma (HCC) patients after curative resection. OBJECTIVE: We aimed to develop a long non-coding RNA (lncRNA) based signature to predict early recurrence. METHODS: Using bioinformatics analysis and quantitative reverse transcription PCR (RT-qPCR), we screened for lncRNA candidates that were abnormally expressed in HCC. The expression levels of candidate lncRNAs were analyzed in HCC tissues from 160 patients who underwent curative resection, and a risk model for the prediction of recurrence within 1 year (early recurrence) of HCCs was constructed with linear support vector machine (SVM). RESULTS: A lncRNA-based classifier (Clnc), which contained nine differentially expressed lncRNAs including AF339810, AK026286, BC020899, HEIH, HULC, MALAT1, PVT1, uc003fpg, and ZFAS1 was constructed. In the test set, this classifier reliably predicted early recurrence (AUC, 0.675; sensitivity, 72.0%; specificity, 63.1%) with an odds ratio of 4.390 (95% CI, 2.120–9.090). Clnc showed higher accuracy than traditional clinical features, including tumor size, portal vein tumor thrombus (PVTT) in predicting early recurrence (AUC, 0.675 vs 0.523 vs 0.541), and had much higher sensitivity than Barcelona Clinical Liver Cancer (BCLC; 72.0% vs 50.0%), albeit their AUCs were comparable (0.675 vs 0.678). Moreover, combining Clnc with BCLC significantly increased the AUC, compared with Clnc or BCLC alone in predicting early recurrence (all P< 0.05). Finally, logistic and Cox regression analysis suggested that Clnc was an independent prognostic factor and associated with the early recurrence and recurrence-free survival of HCC patients after resection, respectively (all P= 0.001). CONCLUSIONS: Our lncRNA-based classifier Clnc can predict early recurrence of patients undergoing surgical resection of HCC.


In agriculture the major problem is leaf disease identifying these disease in early stage increases the yield. To reduce the loss identifying the various disease is very important. In this work , an efficient technique for identifying unhealthy tomato leaves using a machine learning algorithm is proposed. Support Vector Machines (SVM) is the methodology of machine learning , and have been successfully applied to a number of applications to identify region of interest, classify the region. The proposed algorithm has three main staggers, namely preprocessing, feature extraction and classification. In preprocessing, the images are converted to RGB and the average filter is used to eliminate the noise in the input image. After the pre-processing stage, features such as texture, color and shape are extracted from each image. Then, the extracted features are presented to the classifier to classify an input tomato leaf as a healthy or unhealthy image. For classification, in this paper, a multi-kernel support vector machine (MKSVM) is used. The performance of the proposed method is analysed on the basis of different metrics, such as accuracy, sensitivity and specificity. The images used in the test are collected from the plant village. The proposed method implemented in MATLAB.


Electronics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 647
Author(s):  
Kathiravan Srinivasan ◽  
Nivedhitha Mahendran ◽  
Durai Raj Vincent ◽  
Chuan-Yu Chang ◽  
Shabbir Syed-Abdul

Unipolar depression (UD), also referred to as clinical depression, appears to be a widespread mental disorder around the world. Further, this is a vital state related to a person’s health that influences his/her daily routine. Besides, this state also influences the person’s frame of mind, behavior, and several body functionalities like sleep, appetite, and also it can cause a scenario where a person could harm himself/herself or others. In several cases, it becomes an arduous task to detect UD, since, it is a state of comorbidity. For that reason, this research proposes a more convenient approach for the physicians to detect the state of clinical depression at an initial phase using an integrated multistage support vector machine model. Initially, the dataset is preprocessed using multiple imputation by chained equations (MICE) technique. Then, for selecting the appropriate features, the support vector machine-based recursive feature elimination (SVM RFE) is deployed. Subsequently, the integrated multistage support vector machine classifier is built by employing the bagging random sampling technique. Finally, the experimental outcomes indicate that the proposed integrated multistage support vector machine model surpasses methods such as logistic regression, multilayer perceptron, random forest, and bagging SVM (majority voting), in terms of overall performance.


2020 ◽  
Vol 14 (3) ◽  
pp. 269-279
Author(s):  
Hayet Djellali ◽  
Nacira Ghoualmi-Zine ◽  
Souad Guessoum

This paper investigates feature selection methods based on hybrid architecture using feature selection algorithm called Adapted Fast Correlation Based Feature selection and Support Vector Machine Recursive Feature Elimination (AFCBF-SVMRFE). The AFCBF-SVMRFE has three stages and composed of SVMRFE embedded method with Correlation based Features Selection. The first stage is the relevance analysis, the second one is a redundancy analysis, and the third stage is a performance evaluation and features restoration stage. Experiments show that the proposed method tested on different classifiers: Support Vector Machine SVM and K nearest neighbors KNN provide a best accuracy on various dataset. The SVM classifier outperforms KNN classifier on these data. The AFCBF-SVMRFE outperforms FCBF multivariate filter, SVMRFE, Particle swarm optimization PSO and Artificial bees colony ABC.


Author(s):  
JUANA CANUL-REICH ◽  
LAWRENCE O. HALL ◽  
DMITRY B. GOLDGOF ◽  
JOHN N. KORECKI ◽  
STEVEN ESCHRICH

Gene-expression microarray datasets often consist of a limited number of samples with a large number of gene-expression measurements, usually on the order of thousands. Therefore, dimensionality reduction is critical prior to any classification task. In this work, the iterative feature perturbation method (IFP), an embedded gene selector, is introduced and applied to four microarray cancer datasets: colon cancer, leukemia, Moffitt colon cancer, and lung cancer. We compare results obtained by IFP to those of support vector machine-recursive feature elimination (SVM-RFE) and the t-test as a feature filter using a linear support vector machine as the base classifier. Analysis of the intersection of gene sets selected by the three methods across the four datasets was done. Additional experiments included an initial pre-selection of the top 200 genes based on their p values. IFP and SVM-RFE were then applied on the reduced feature sets. These results showed up to 3.32% average performance improvement for IFP across the four datasets. A statistical analysis (using the Friedman/Holm test) for both scenarios showed the highest accuracies came from the t-test as a filter on experiments without gene pre-selection. IFP and SVM-RFE had greater classification accuracy after gene pre-selection. Analysis showed the t-test is a good gene selector for microarray data. IFP and SVM-RFE showed performance improvement on a reduced by t-test dataset. The IFP approach resulted in comparable or superior average class accuracy when compared to SVM-RFE on three of the four datasets. The same or similar accuracies can be obtained with different sets of genes.


2007 ◽  
Vol 3 ◽  
pp. 117693510700300 ◽  
Author(s):  
Changyu Shen ◽  
Timothy E Breen ◽  
Lacey E Dobrolecki ◽  
C. Max Schmidt ◽  
George W. Sledge ◽  
...  

Introduction As an alternative to DNA microarrays, mass spectrometry based analysis of proteomic patterns has shown great potential in cancer diagnosis. The ultimate application of this technique in clinical settings relies on the advancement of the technology itself and the maturity of the computational tools used to analyze the data. A number of computational algorithms constructed on different principles are available for the classification of disease status based on proteomic patterns. Nevertheless, few studies have addressed the difference in the performance of these approaches. In this report, we describe a comparative case study on the classification accuracy of hepatocellular carcinoma based on the serum proteomic pattern generated from a Surface Enhanced Laser Desorption/Ionization (SELDI) mass spectrometer. Methods Nine supervised classification algorithms are implemented in R software and compared for the classification accuracy. Results We found that the support vector machine with radial function is preferable as a tool for classification of hepatocellular carcinoma using features in SELDI mass spectra. Among the rest of the methods, random forest and prediction analysis of microarrays have better performance. A permutation-based technique reveals that the support vector machine with a radial function seems intrinsically superior in learning from the training data since it has a lower prediction error than others when there is essentially no differential signal. On the other hand, the performance of the random forest and prediction analysis of microarrays rely on their capability of capturing the signals with substantial differentiation between groups. Conclusions Our finding is similar to a previous study, where classification methods based on the Matrix Assisted Laser Desorption/Ionization (MALDI) mass spectrometry are compared for the prediction accuracy of ovarian cancer. The support vector machine, random forest and prediction analysis of microarrays provide better prediction accuracy for hepatocellular carcinoma using SELDI proteomic data than six other approaches.


Sign in / Sign up

Export Citation Format

Share Document