ARID1A Mutation from Targeted Next-Generation Sequencing Predicts Primary Resistance to Gemcitabine and Cisplatin Chemotherapy in Advanced Biliary Tract Cancer (original) (raw)

Fig. 1Genomic alteration associated with anatomic locations of biliary tract cancer. Oncoplot showing non-silent mutation counts for individual tumors (top), frequently mutated top 40 genes (middle), and other clinical factors including center, sex, age, sequencing panel, and MMR status (bottom). CCA, cholangiocarcinoma; dMMR, deficient mismatch repair; EHC, extrahepatic cholangiocarcinomar; GB, gallbladder cancer; MMR, mismatch repair; MSI, microsatellite instability; MSS, microsatellite stable; NGS, next generation sequencing.

Fig. 2Alteration pattern associated with anatomic locations of biliary tract cancer. (A) Bar plot showing the relative fraction of alterations for ERBB2 amplification and IDH1. p-value was calculated using the chi-square test. (B) Stacked bap plot for single nucleotide changes for KRAS according to the anatomic location. (C) Circos plot representing fusion events. Red color indicates extrahepatic while green color indicates intrahepatic location. (D) Diagram for pathway alteration presenting the percentage of samples for each anatomic location with respect to DNA damage response, ErbB/HER signaling, Wnt/β-catenin, TGF-β signaling, fibroblast growth factor and AMPK pathways, as well as the SWI/SNF complex, respectively. CCA, cholangiocarcinoma; GB, gallbladder cancer.

Fig. 3Prediction of clinical outcomes according to prognostic genes. (A) Forest plot showing significant genes, for predicting disease progression (ARID1A, BRCA2, and STK11) after first-line chemotherapy from multivariate logistic regression. (B) Kaplan-Meier plot demonstrating survival difference for progression-free survival according to ARID1A in total biliary tract cancer patients. (C) Stacked bar plot indicating optimal response after first-line chemotherapy according to ARID1A mutation in EHC. (D) Kaplan-Meier plot presenting survival difference for progression-free survival according to ARID1A in EHC. p-value was estimated using the log-rank test. CCA, cholangiocarcinoma; CI, confidence interval; EHC, extrahepatic cholangiocarcinomar; OR, odds ratio; PD, progressive disease; PR, partial response; SD, stable disease.

Fig. 4Drug sensitivity of cancer cells according to ARID1A mutation. (A) Volcano plot presenting sensitive or resistant drugs according to ARID1A mutation. p-value was estimated using the student’s t test. (B) Grouped bar plot showing ARID1A-specific drug sensitivity for cisplatin according to cancer types. p-value was calculated using the Wilcoxon signed-rank test. DMSO, dimethyl sulfoxide; NA, not available.