Treatment monitoring of colorectal cancer by integrated analysis of plasma concentration and sequencing of circulating t
- PDF / 2,678,385 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 89 Downloads / 156 Views
LETTER TO THE EDITOR
Open Access
Treatment monitoring of colorectal cancer by integrated analysis of plasma concentration and sequencing of circulating tumor DNA Yu-Min Yeh1, Peng-Chan Lin1, Chung-Ta Lee2, Shang-Hung Chen1, Bo-Wen Lin3, Shao-Chieh Lin3, Po-Chuan Chen3, Ren-Hao Chan3 and Meng-Ru Shen4,5*
Abstract Circulating cell-free DNA (cfDNA) analysis is an important tool for cancer monitoring. The patient-specific mutations identified in colorectal cancer (CRC) tissues are usually used to design the cfDNA analysis. Despite high specificity in predicting relapse, the sensitivity in most studies is around 40–50%. To improve this weakness, we designed a cfDNA panel according to the CRC genomic landscape and recurrent-specific mutations. The pathological variants in cfDNA samples from 60 CRC patients were studied by a next-generation sequencing (NGS) method incorporating the dual molecular barcode. Interestingly, patients in the disease positive group had a significantly higher cfDNA concentration than those in the disease negative group. Based on receiver operating characteristic analysis, the cfDNA concentration of 7 ng/mL was selected into the analytical workflow. The sensitivity in determining the disease status was 72.4%, which represented a considerable improvement on prior studies, and the specificity remained high at 80.6%. Compared to standard imaging and laboratory studies, earlier detection of residual disease and clinical benefits were shown on two cases by this cfDNA assay. We conclude this integrative framework of cfDNA analytical pipeline with a satisfactory sensitivity and specificity could be used in postoperative CRC surveillance. Keywords: Colorectal cancer, Circulating cell-free DNA, Cell-free DNA concentration, Molecular barcode, Nextgeneration sequencing
Main text The standard care for CRC patients without distant metastasis is surgical resection of the primary tumor with en bloc removal of the regional lymph nodes. Despite the aggressive use of adjuvant FOLFOX chemotherapy, recurrence develops in a third of patients with stage III * Correspondence: [email protected] 4 Department of Pharmacology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 5 Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138 Sheng-Li Road, Tainan 704, Taiwan Full list of author information is available at the end of the article
or high-risk stage II disease. Moreover, FOLFOX chemotherapy causes a long-lasting neurotoxicity, negatively impacting the quality of life of survivors [1, 2]. The development of biomarkers to identify CRC patients who truly have residual disease will allow patients to be treated with appropriate adjuvant chemotherapy and avoid unnecessary treatment-related toxicity in the adjuvant setting. Circulating cfDNA are short fragmented DNAs which are detectable in plasma [3]. Several studies selected the patient-specific mutations identified in
Data Loading...
