Fig. 1
BRAF mutation is associated with radioresistance in colorectal cancer. (A) Flowchart for analyzing the relationship between radiation sensitivity and gene mutations based on organoid models. A biobank containing 116 patient-derived organoids was constructed. From these, 29 samples with both radiation therapy sensitivity data and WES data were selected for correlation analysis. (B) The tumor stage and histological type distribution of the 29 selected PDOs. (C) Overview of somatic mutations in known driver genes found in 29 PDOs. Organoids were grouped based on the size ratio at 24 days after 8 Gy radiation to the area on day 0. Those with a ratio greater than the median (135.03%) were classified as the radiation-resistant group (n = 14), while those with a ratio less than or equal to the median were classified as the sensitive group (n = 15). D-H) The size ratios at 24 days post 8 Gy radiation for organoids with the wild-type (WT) and mutated forms (MT) of the top 5 most frequently mutated genes (TP53, APC, FBXW7, KRAS and BRAF) were analyzed by student’s t-test to compare their radiation sensitivity (BRAF mutated vs. wild-type: 355.3% vs. 132.8%, p = 0.0004). I) Inclusion flowchart of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy. J) Kaplan–Meier analysis of the probability of survival in patients with BRAFV600E mutation and BRAF wild type (Log-rank test, HR: 8.19, 95% CI: 1.24–54.06, p<0.0001). K) The distribution of TRG after neoadjuvant chemoradiotherapy was compared between patients with BRAF wild-type (WT) and those with BRAFV600E mutation (MT). See also Table S1(Supporting Information)