RESUMO
Timely accurate and cost-efficient detection of colorectal cancer (CRC) is of great clinical importance. This study aims to establish prediction models for detecting CRC using plasma cell-free DNA (cfDNA) fragmentomic features. Whole-genome sequencing (WGS) was performed on cfDNA from 620 participants, including healthy individuals, patients with benign colorectal diseases and CRC patients. Using WGS data, three machine learning methods were compared to build prediction models for the stratification of CRC patients. The optimal model to discriminate CRC patients of all stages from healthy individuals achieved a sensitivity of 92.31% and a specificity of 91.14%, while the model to separate early-stage CRC patients (stage 0-II) from healthy individuals achieved a sensitivity of 88.8% and a specificity of 96.2%. Additionally, the cfDNA fragmentation profiles reflected disease-specific genomic alterations in CRC. Overall, this study suggests that cfDNA fragmentation profiles may potentially become a noninvasive approach for the detection and stratification of CRC.
Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Detecção Precoce de Câncer/métodos , Idoso , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Aprendizado de Máquina , Adulto , Sequenciamento Completo do Genoma/métodos , Fragmentação do DNARESUMO
Most hepatocellular carcinomas (HCCs) are associated with hepatitis B virus infection (HBV) in China. Early detection of HCC can significantly improve prognosis but is not yet fully clinically feasible. This study aims to develop methods for detecting HCC and studying the carcinogenesis of HBV using plasma cell-free DNA (cfDNA) whole-genome sequencing (WGS) data. Low coverage WGS was performed for 452 participants, including healthy individuals, hepatitis B patients, cirrhosis patients, and HCC patients. Then the sequencing data were processed using various machine learning models based on cfDNA fragmentation profiles for cancer detection. Our best model achieved a sensitivity of 87.10% and a specificity of 88.37%, and it showed an increased sensitivity with higher BCLC stages of HCC. Overall, this study proves the potential of a non-invasive assay based on cfDNA fragmentation profiles for the detection and prognosis of HCC and provides preliminary data on the carcinogenic mechanism of HBV.