Fig. 1
Pitavastatin and atorvastatin are identified as putative treatments for metastatic CMS4 CRC. (A) PRISM screening, a high-throughput DNA-barcoding technique, is used to analyze the cell viability of 35 CRC cells treated with 4,686 compounds. PRISM drug sensitivity represents the log2-fold change in cell proliferation rate following drug treatment compared with an untreated group. Mann-Whitney U tests (p < 0.05) were used to identify specifically sensitive drugs in metastatic CRC cells and CMS-specific groups. (B-C) The numbers of compounds and on-market drugs at the intersection of drug candidates representing five groups (i.e., CMS1-4 specific drugs and metastasis-specific drugs). The horizontal bar represents the set size (i.e., the total number of drugs identified as candidates from each of the five groups). In contrast, the vertical bar represents the size of the intersection (i.e., the number of drugs included in each intersecting set). (D-E) Illustrations of the specific sensitivity of pitavastatin, atorvastatin, lovastatin, simvastatin, and mevastatin against metastatic (*Metastatic cells compared to primary cells) and CMS4 cells (* CMS4 cells compared to other CMS cells). (F) Analysis of the PRISM database used to compare the sensitivity of CRC cells to pitavastatin, atorvastatin, and 5-FU. There was no pitavastatin sensitivity data for SW837 cells found in the database. The cut-off value of drug sensitivity was smaller than 0.3. One symbol represents p < 0.05; two symbols indicate p < 0.01