Additional file 3 of An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy

Additional file3. Fig S1-S11.pdf. Fig. S1.The 5-gene dasatinib sensitivity (Dasa-S) signature score predicted the trendof dasatinib sensitivity in multiple CRC cell lines (n=50). Fig.S2. The EMT genes were strongly associated with regionalmetastasis and disease recurrence in 2202 CRC tumors. Fig. S3.The CMS4 subtype was strongly correlated with the 13-gene MEKi“bypass”-resistance (13-gene BP), PC1, EMT, SRC activation and 5-gene Dasa-Ssignature scores in 1485 primary CRC tumors. Fig.S4. The CMS4 subtype was strongly correlated with the 13-geneMEKi “bypass”-resistance (13-gene BP), PC1, EMT, SRC activation and 5-geneDasa-S signature scores in 764 metastatic CRC tumors. Fig. S5.Scatter plots of Hu-Lgr5-ISC, Hu-EphB2-ISC, Hu-Late TA, and Hu-Proliferation vsEMT signature scores, respectively in Marisa 585 CRCs. Fig. S6.Scatter plots of Hu-Lgr5-ISC, Hu-EphB2-ISC, Hu-Late TA, and Hu-Proliferation vsEMT signature scores in TCGA 677 CRCs. Fig. S7.Spearman correlation heatmap of CMS1-4* scores, signature scores andEMT-associated genes in Marisa 585 CRC tumors. Fig.S8. Spearman correlation heatmap of CMS1-4* scores, signaturescores and EMT-associated genes in TCGA 677 CRC tumors. Fig. S9. Nodistinct association of MUT vs WT APC/TP53 tumors with the CMS subtypes. Fig. S10. Correlationanalysis of 154 CRC cell lines and in vitro drug treatment of HCT116 cells withMEKi + SRCi in CSC vs. non-CSC media. Fig.S11. In vitro drug treatment of LIM2405and HT29 cells with MEKi + SRCi in CSC vs. non-CSC media.

附加文件3：图S1~S11.pdf。
图S1：5基因达沙替尼敏感性（Dasa-S）特征评分可预测50株结直肠癌（CRC）细胞系的达沙替尼敏感性变化趋势。
图S2：上皮间质转化（Epithelial-Mesenchymal Transition, EMT）相关基因在2202例结直肠癌肿瘤中与区域转移及疾病复发显著相关。
图S3：在1485例原发性结直肠癌肿瘤中，CMS4亚型与13基因丝裂原活化蛋白激酶激酶抑制剂（MEK inhibitor, MEKi）“旁路”耐药（13-gene BP）特征评分、PC1、EMT、SRC激活及5基因Dasa-S特征评分均显著相关。
图S4：在764例转移性结直肠癌肿瘤中，CMS4亚型与13基因MEKi“旁路”耐药（13-gene BP）特征评分、PC1、EMT、SRC激活及5基因Dasa-S特征评分均显著相关。
图S5：在Marisa队列585例结直肠癌样本中，分别绘制Hu-Lgr5-ISC、Hu-EphB2-ISC、Hu-Late TA及Hu-Proliferation特征评分与EMT特征评分的散点图。
图S6：在TCGA队列677例结直肠癌样本中，分别绘制Hu-Lgr5-ISC、Hu-EphB2-ISC、Hu-Late TA及Hu-Proliferation特征评分与EMT特征评分的散点图。
图S7：在Marisa队列585例结直肠癌肿瘤中，绘制CMS1-4*评分、各特征评分及EMT相关基因的Spearman相关热图。
图S8：在TCGA队列677例结直肠癌肿瘤中，绘制CMS1-4*评分、各特征评分及EMT相关基因的Spearman相关热图。
图S9：APC/TP53突变型（mutant, MUT）与野生型（wild type, WT）肿瘤与CMS亚型无显著关联。
图S10：针对154株结直肠癌细胞系，以及在癌症干细胞（Cancer Stem Cell, CSC）培养基与非癌症干细胞（non-CSC）培养基中对HCT116细胞进行MEKi联合SRC抑制剂（SRC inhibitor, SRCi）体外药物处理的相关性分析。
图S11：在CSC培养基与non-CSC培养基中，分别对LIM2405及HT29细胞进行MEKi联合SRCi的体外药物处理。