Evaluation of Somatic Mutation Spectrum as Biomarker for Survival Outcome in Chinese CRC

Colorectal cancer (CRC), as one of the common malignant tumors with high morbidity and mortality, is a major health threat in China. Surgical resection is the conventional treatment for early and intermediate stage CRC, chemotherapy is the main treatment for late stage CRC. Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 170bp, mixed with cell free DNA (cfDNA) of other sources in blood circulation. Although the mechanisms of its release have not been fully addressed, apoptosis and/or necrosis of tumor cells and serum exosome are considered as its main source, which makes it a genomic reservoir of different tumor clones. Also, as its half-life is up to hours, ctDNA is reflecting the most up-to-date status of tumor genome. Hence, it allows for noninvasive molecular characterization of tumors,which can be qualitative, quantitative and used for disease monitoring. The possibility of that ctDNA could be used to detect micrometastatic disease in patients received surgical resection was suggested in several studies. Using Next Generation Sequencing (NGS), Newman et al. have shown that the serum level of ctDNA was correlated with tumor progress and prognosis in NSCLC. Isaac et al. demonstrated the postoperative ctDNA level was associated with breast cancer progression, and it was more sensitive compared to CT scan for predicting the early relapse. Tie et al. examined the postoperative ctDNA level of 1046 plasma samples from a prospective cohort of 230 patients with resected stage II CRC by NGS, and their results demonstrated that recurrence happened in 79% of the patients with positive postoperative ctDNA at median follow-up of 27 months, versus 9.8% in the negative postoperative ctDNA group.