Enhancing Lung Cancer Classification through Integration of Liquid Biopsy Multi-Omics Data with Machine Learning Techniques

Early detection of lung cancer is crucial for patient survival and treatment. Recent advancements in next-generation sequencing (NGS) analysis enable cell-free DNA (cfDNA) liquid biopsy to detect changes, like chromosomal rearrangements, somatic mutations, and copy number variations (CNVs), in cancer. Machine learning (ML) analysis using cancer markers is a highly promising tool for identifying patterns and anomalies in cancers, making the development of ML-based analysis methods essential. We collected blood samples from 92 lung cancer patients and 80 healthy individuals to analyze the distinction between them. The detection of lung cancer markers Cyfra21 and carcinoembryonic antigen (CEA) in blood revealed significant differences between patients and controls. We performed machine learning analysis to obtain AUC values via Adaptive Boosting (AdaBoost), Multi-Layer Perceptron (MLP), and Logistic Regression (LR) using cancer markers, cfDNA concentrations, and CNV screening. Furthermore, combining the analysis of all multi-omics data for ML showed higher AUC values compared with analyzing each element separately, suggesting the potential for a highly accurate diagnosis of cancer. Overall, our results from ML analysis using multi-omics data obtained from blood demonstrate a remarkable ability of the model to distinguish between lung cancer and healthy individuals, highlighting the potential for a diagnostic model against lung cancer

Advances in methylation analysis of liquid biopsy in early cancer detection of colorectal and lung cancer

Abstract Methylation patterns in cell-free DNA (cfDNA) have emerged as a promising genomic feature for detecting the presence of cancer and determining its origin. The purpose of this study was to evaluate the diagnostic performance of methylation-sensitive restriction enzyme digestion followed by sequencing (MRE-Seq) using cfDNA, and to investigate the cancer signal origin (CSO) of the cancer using a deep neural network (DNN) analyses for liquid biopsy of colorectal and lung cancer. We developed a selective MRE-Seq method with DNN learning-based prediction model using demethylated-sequence-depth patterns from 63,266 CpG sites using SacII enzyme digestion. A total of 191 patients with stage I–IV cancers (95 lung cancers and 96 colorectal cancers) and 126 noncancer participants were enrolled in this study. Our study showed an area under the receiver operating characteristic curve (AUC) of 0.978 with a sensitivity of 78.1% for colorectal cancer, and an AUC of 0.956 with a sensitivity of 66.3% for lung cancer, both at a specificity of 99.2%. For colorectal cancer, sensitivities for stages I–IV ranged from 76.2 to 83.3% while for lung cancer, sensitivities for stages I–IV ranged from 44.4 to 78.9%, both again at a specificity of 99.2%. The CSO model's true-positive rates were 94.4% and 89.9% for colorectal and lung cancers, respectively. The MRE-Seq was found to be a useful method for detecting global hypomethylation patterns in liquid biopsy samples and accurately diagnosing colorectal and lung cancers, as well as determining CSO of the cancer using DNN analysis. Trial registration: This trial was registered at ClinicalTrials.gov (registration number: NCT 04253509) for lung cancer on 5 February 2020, https://clinicaltrials.gov/ct2/show/NCT04253509 . Colorectal cancer samples were retrospectively registered at CRIS (Clinical Research Information Service, registration number: KCT0008037) on 23 December 2022, https://cris.nih.go.kr , https://who.init/ictrp . Healthy control samples were retrospectively registered