Identification of a cancer-associated fibroblast signature for predicting prognosis and immunotherapeutic responses in bladder urothelial carcinoma

Figures & data

Figure 1. WGCNA results. Relationship between R² and different soft thresholds (a). TCGA-BLCA (D). GSE32894. Mean value of adjacency coefficients of genes corresponding to soft thresholds (B). TCGA-BLCA (E). GSE32894. The genes with similar expression patterns were clustered into co-expression modules using a cluster dendrogram (C). TCGA-BLCA (F). GSE32894. Heat map of association between gene modules and CAF traits (G). TCGA-BLCA (I). GSE32894. Scatter plot of the correlation between MM and GS in blue (H) and brown (J) modules.

Figure 2. (A). Venn plot showing the intersection of TCGA-STAD blue module and GSE32894 brown module genes. GO (B) and KEGG (C) results of the hub genes. (D-E). LASSO regression analysis with adjustment parameters (λ) calculated according to partial likelihood bias and cross-validation.

Figure 3. Kaplan–meier analyses of patients having high and low CAF scores (a). TCGA-BLCA, (D). GSE32894, (G) IMvigor210. Univariate Cox regression analysis (B). TCGA-BLCA, (E). GSE32894, (H) IMvigor210. Multivariate Cox regression analysis (C). TCGA-BLCA, (F). GSE32894, (I) IMvigor210. (J). nomogram of the TCGA-BLCA cohort. (K). time-dependent ROC curve of the nomogram. (L). calibration curve.

Figure 4. GSEA of KEGG Pathway in high (A) and low (B) CAF score groups (C). Comparison of some immunotherapy-related genes between patients with high and low CAF scores. Waterfall plot of somatic mutations in patients with high (D) and low (E) CAF scores. (F). correlation analysis of TMB and CAF scores. (G). Comparison of TMB between high- and low-CAF score groups.

Table 1. Association of CAF scores with somatic variants.

Gene	H-wild	H-mutation	L-wild	L-mutation	P value
FBN2	195(97.5%)	5(2.5%)	177(89.39%)	21(10.61%)	0.002
NAV3	195(97.5%)	5(2.5%)	178(89.9%)	20(10.1%)	0.004
ADGRV1	188(94%)	12(6%)	168(84.85%)	30(15.15%)	0.005
NFE2L2	181(90.5%)	19(9.5%)	193(97.47%)	5(2.53%)	0.007
LRP1B	188(94%)	12(6%)	169(85.35%)	29(14.65%)	0.008
DYNC1H1	193(96.5%)	7(3.5%)	177(89.39%)	21(10.61%)	0.010
HUWE1	195(97.5%)	5(2.5%)	181(91.41%)	17(8.59%)	0.015
USH2A	191(95.5%)	9(4.5%)	175(88.38%)	23(11.62%)	0.015
AHNAK	188(94%)	12(6%)	171(86.36%)	27(13.64%)	0.017
SZT2	196(98%)	4(2%)	183(92.42%)	15(7.58%)	0.018
TP53	92(46%)	108(54%)	115(58.08%)	83(41.92%)	0.021
CCDC88A	193(96.5%)	7(3.5%)	179(90.4%)	19(9.6%)	0.024
MED13	190(95%)	10(5%)	175(88.38%)	23(11.62%)	0.027
SPTAN1	187(93.5%)	13(6.5%)	171(86.36%)	27(13.64%)	0.028
PRKDC	193(96.5%)	7(3.5%)	180(90.91%)	18(9.09%)	0.036
CHD4	195(97.5%)	5(2.5%)	183(92.42%)	15(7.58%)	0.037
RELN	190(95%)	10(5%)	176(88.89%)	22(11.11%)	0.040
DNAH3	190(95%)	10(5%)	176(88.89%)	22(11.11%)	0.040
DIDO1	190(95%)	10(5%)	176(88.89%)	22(11.11%)	0.040
ELF3	183(91.5%)	17(8.5%)	167(84.34%)	31(15.66%)	0.042
AHR	194(97%)	6(3%)	182(91.92%)	16(8.08%)	0.046

Figure 5. Comparison of CAF scores between immunotherapy responders and nonresponders (A). TCGA-BLCA, (C). GSE32894, (F) IMvigor210. Distribution of responders and nonresponders in the high- and low-CAF score groups (B). TCGA-BLCA, (D). GSE32894, (G) IMvigor210. AUC of ROC curve (C). TCGA-BLCA, (E). GSE32894, (H) IMvigor210.

Data availability statement

The datasets generated and analyzed in this study can be found in the Gene Expression Omnibus repository (accession number: GSE32894 and GSE13507), The Cancer Genome Atlas-bladder urothelial carcinoma (TCGA-BLCA), and IMvigor210 databases.