Journal: Molecular cancer therapeutics

Article Title: A four-gene decision tree signature classification of triple-negative breast cancer: Implications for targeted therapeutics

doi: 10.1158/1535-7163.MCT-18-0243

Figure Lengend Snippet: Identification of concurrent cancer gene sets with CONEXIC. (A) Research design and workflow. After selecting a decision tree, a molecular characterisation of the subtypes was performed in two discovery and five validation sets. Treatment response to DNA damaging agents was assessed in three clinical trials. (B) The number of gene sets, decision trees and modulators identified by the CONEXIC algorithm in Guy’s TNBC and METABRIC TNBC. Overlap in gene set composition between the two cohorts was assessed using a one-sided Fisher’s exact test. (C) Level plot of concurrent gene sets between Guy’s TNBC and METABRIC TNBC. Dark grey boxes indicate gene sets with significantly overlapping genes. Black boxes, as dark grey boxes, in addition to overlapping modulators. Gene sets are ordered by size, as indicated by the scales. (D) Venn diagram depicting the number of common genes between Guy’s-set 27, Guy’s-set 33, and METABRIC-set 15.

Article Snippet: In the metastatic TNBC Sanofi Phase II trial, neither the BL1 nor the MC6 subtype was predictive of the overall response rate (ORR) ( and Supplementary Table S18 ).

Techniques: Biomarker Discovery, Clinical Proteomics

Journal: Molecular cancer therapeutics

Article Title: A four-gene decision tree signature classification of triple-negative breast cancer: Implications for targeted therapeutics

doi: 10.1158/1535-7163.MCT-18-0243

Figure Lengend Snippet: TNBC cohorts classified using the METABRIC-set 15 four-gene decision tree signature. Pie charts illustrating the proportion of the MC subtypes in four primary invasive TNBC cohorts, namely METABRIC TNBC, Guy’s TNBC, TNBC616 and TCGA TNBC, as well as three clinical TNBC studies, including Sanofi Phase II, Sanofi Phase III and PrECOG 0105. The total number of tumours in each cohort is listed in brackets. The percentage for each subgroup is shown next to the respective pies.

Article Snippet: In the metastatic TNBC Sanofi Phase II trial, neither the BL1 nor the MC6 subtype was predictive of the overall response rate (ORR) ( and Supplementary Table S18 ).

Techniques:

Journal: Molecular cancer therapeutics

Article Title: A four-gene decision tree signature classification of triple-negative breast cancer: Implications for targeted therapeutics

doi: 10.1158/1535-7163.MCT-18-0243

Figure Lengend Snippet: Molecular characterisation of the MC subtypes in METABRIC TNBC. (A) The four-gene decision tree underlying the MC subtypes is shown, followed by a heat map representing the expression levels of the four modulatory genes. The coloured bars represent sample-specific characteristics, including PAM50, IntClust, TNBCtype-4, CIN70 signature and the immunomodulatory status. The heatmap at the bottom illustrates the enrichment of immune gene signatures. (B) (left) MAPK inactivation scores, calculated by summarising the expression levels of DUSP4, DUSP5, DUSP6, DUSP10 and SPRED2, in MC6-TNBCs (magenta) and the remaining TNBCs (grey). Significance was assessed using Wilcoxon rank-sum tests. (right) Z-scores for the DUSP6 gene set were obtained using ssGSEA. Significance was assessed using a Wilcoxon rank-sum test. (C) Boxplots displaying the CIN70 signature (left) and NtAI (right) in MC6-TNBCs (magenta) and the remaining TNBCs (grey). Significance was assessed using Wilcoxon rank-sum tests.

Article Snippet: In the metastatic TNBC Sanofi Phase II trial, neither the BL1 nor the MC6 subtype was predictive of the overall response rate (ORR) ( and Supplementary Table S18 ).

Techniques: Expressing