A Multi-omics Study of BRAF V600E Mutant Colorectal Cancer

As an oncogenic gene, BRAF V600E subverts the need for continuous upstream activation and overcomes negative feedback signals that terminate pathway activation. In colorectal cancer, BRAF V600E mutations are associated with older age, right colon primary tumors and female gender, as well as reduced chemotherapy sensitivity and poor prognosis. In addition to a poor prognosis, BRAF V600E-mutant colorectal cancer is associated with a higher incidence of peritoneal metastasis, resulting in tumor-related symptoms such as pain, ascites, gastrointestinal and urinary obstruction, which severely compromise patients' quality of life. Although there is a trend that BRAF V600E mutant patients who receive high-intensity chemotherapy have longer progression-free survival (PFS), the prognosis of the BRAF V600E mutant population remains dismal and approximately 40% of patients do not respond to first-line high-intensity chemotherapy. In addition, the response rate of combined targeted therapy is limited to around 25% and the duration of anti-epidermal growth factor receptor (EGFR) and anti-BRAF is around 4 months due to the presence of bypass activation. What's more, patients with BRAF V600E mutation and mismatch repair-proficient (pMMR) also had a poor response to anti-programmed death-1 (PD-1) therapy. The tumor heterogeneity and tumour immune microenvironment of BRAF V600E mutant colorectal cancer need to be investigated. The study seeks to identify novel immune biomarkers, therapeutic targets, and signaling pathways, and to enable molecular subtyping for precision treatment and personalized management of BRAF-mutant CRC patients.

Inclusion criteria

• Written informed consent to study procedures;
• Men and women aged ≧18 years;
• Diagnosis of histologically or cytologically confirmed colorectal cancer;
• First-generation sequencing or next-generation sequencing at any time prior to screening confirms the presence of BRAF V600E mutation in tumor tissue.

Exclusion criteria

• Patients with serious heart disease, hypertension, cerebral hemorrhage or uncontrollable systemic diseases (such as: diabetes, hypertension, pulmonary fibrosis and acute pneumonia);
• Women who are pregnant or nursing;
• Unable to co-operate in sampling;
• Received more than two prior regimens of systemic cancer therapy for colorectal cancer.