Figure 8. FOXA1 confers immunotherapy resistance in bladder cancer.

(A) Comparison of FOXA1 mRNA level among 31 cancer types in TCGA database, including PRAD (prostate adenocarcinoma), BRCA (breast invasive carcinoma), BLCA (bladder urothelial carcinoma), LUAD (lung adenocarcinoma), LIHC (liver hepatocellular carcinoma), CESC (cervical squamous cell carcinoma and endocervical adenocarcinoma), CHOL (cholangiocarcinoma), LUSC (lung squamous cell carcinoma), COAD (colon adenocarcinoma), READ (rectum adenocarcinoma), PAAD (pancreatic adenocarcinoma), UCEC (uterine corpus endometrial carcinoma), UCS (uterine carcinosarcoma), HNSC (head and neck squamous cell carcinoma), MESO (mesothelioma), TGCT (testicular germ cell tumors), OV (ovarian serous cystadenocarcinoma), THCA (thyroid carcinoma), SARC (sarcoma), SKCM (skin cutaneous melanoma), ACC (adrenocortical carcinoma), KIRC (kidney renal clear cell carcinoma), PCPG (pheochromocytoma and paraganglioma), KIRP (kidney renal papillary cell carcinoma), DLBC (lymphoid neoplasm diffuse large B-cell lymphoma), THYM (thymoma), LGG (brain lower grade glioma), KICH (kidney chromophobe), GBM (glioblastoma multiforme), LAML (acute myeloid leukemia), and UVM (uveal melanoma). (B) Heatmaps show the negative correlation of FOXA1 expression with the expression levels of IFN response signature genes and APM genes in TCGA cohort of bladder cancers. Samples are ranked based on FOXA1 transcript levels. Statistical significance was determined by Pearson’s correlation test. (C) The correlation between FOXA1 level and TMB in TCGA cohort of bladder cancers. Statistical significance was determined by Pearson’s correlation test. (D) Progression-free survival of patients with FOXA1-low or -high urothelial carcinomas treated with anti–PD-1 immunotherapy. Statistical significance was determined by log-rank (Mantel-Cox) test. See also Supplemental Figure 18 and Supplemental Table 3 for FOXA1 IHC staining and patient clinical information, respectively.