Journal Article

Fragment length profiles of cancer mutations enhance detection of circulating tumor DNA in patients with early-stage hepatocellular carcinoma

Duong, Minh-Long, Kim, Van-Vu, Tran, Thuy Thi Thu, Tran, Vu Uyen, Phan, Boi Hoan Huu, Tran, Le Son, Nguyen, Van-Chu, Nguyen, Quynh-Tho Thi, Nguyen, Hue Hanh Thi, Nguyen, Hoai-Nghia, Tran, Thanh-Huong Thi, Nguyen, Cao Minh, Pham, The-Anh, Ho, Tan Dat, Nguyen, Trong Hieu, Giang, Hoa, Pham, Thu Thuy Thi, Truong, Dinh-Kiet, Phu, Dung Thai Bieu, Nguyen, Que-Tran Bui, Phan, Minh-Duy, Phan, Thanh Hai, Do, Thanh-Thuy Thi, Nguyen, Bao Toan, Nguyen, Thanh Nhan Vo, Bach, Hoai-Phuong Thi, Huynh, Le Anh Khoa, Nguyen, Thanh Dang

2023

Overview

Background Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity. Methods Here, we employed concurrent analysis of cancer-related mutations, and their fragment length profiles to differentiate mutations from different sources. To distinguish persons with HCC (PwHCC) from healthy participants, we built a classification model using three fragmentomic features of ctDNA through deep sequencing of thirteen genes associated with HCC. Results Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%. Conclusions Our study provides a rationale for subsequent clinical evaluation of our assay performance in a large-scale prospective study.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Biomarkers, Tumor - genetics / Biomedical and Life Sciences / Biomedicine / Biopsy / Blood / Cancer Research / Cancer specific mutation / Carcinoma, Hepatocellular - diagnosis / Carcinoma, Hepatocellular - genetics / Care and treatment / Cell free DNA / Circulating Tumor DNA / Data analysis / Diagnosis / Fragmentomics / Gene mutations / Genetic aspects / Health aspects / Health Promotion and Disease Prevention / Hepatocellular carcinoma / Hepatoma / Hospitals / Humans / Liquid biopsy / Liver / Liver cancer / Liver cirrhosis / Liver Neoplasms - diagnosis / Liver Neoplasms - genetics / Medical prognosis / Medicine/Public Health / Metastasis / Mutation / Oncology / Plasma / Prospective Studies / Surgical Oncology / Tumors