By analyse the tissue/blood variant spectrum model using NGS, the present clinical trial aims to elucidate the genetic basis of CRC in Chinese; to establish of CRC genetic map in Chinese patients; to identification new genetic biomarkers, drug and pathways; and to subtyping for precision treatment and management for Chinese CRC patients.

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.

Inclusion Criteria:

Retrospective cohort:

1. The patient had no previous history of tumor prior to the diagnosis of colorectal cancer.
2. The tissue samples of patients were obtained from the radical(stage I-III) or palliative (stage IV) resection of colorectal cancer.
3. The clinical data of patients are complete.
4. The treatment record of the patients after surgery are complete, and the fellow-up data are available.

Prospective cohort:

1. Patients who were diagnosed as stage IV colorectal cancer and planed to received palliative systematic chemotherapy.
2. Paired 10 ml blood and tissue samples should be available
3. The clinical informations of patients and definite pathological diagnosis of colorectal cancer should be obtained
4. Patients agree with the group to follow-up them and provide follow-up informations
5. Performance status ECOG（Eastern Cooperative Oncology Group） score ≤2
6. Informed consent must be obtained from the patient

Exclusion Criteria:

Retrospective cohort:

1. The patient had previous history of tumor prior to colorectal cancer surgery
2. The clinical data of patients are not available

4. The date of treatment after surgery are not integrity, outcome data are not available

Prospective cohort:

1. The patient received a blood transfusion within three months;
2. The patient has active HIV, hepatitis B or hepatitis C infection;
3. pregnant patients;
4. Alcohol or drug users;
5. Other situation that researchers considered might affect the results of the experiment or violate the ethics.

Patients must have baseline evaluations performed prior to the study and must meet all inclusion and exclusion criteria. In addition, the patient of the prospective cohort should be thoroughly informed about the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent. The written informed consent of the prospective cohort should be obtained from the patient prior to enrollment. The following criteria apply to all patients enrolled onto the study unless otherwise specified.