CAFs in chemoresistant tumors are associated with myofibroblastic phenotype
(A) UMAP plot of CAFs, color-coded as chemoresistant (OCC-R1-5) or chemosensitive (OCC-S1-5) cases.
(B) Bar chart showing enrichment of specific biological pathways in CAFs from resistant tumors. Enrichment of a pathway is calculated by comparing the average ssGSEA values of Hallmark gene sets in CAFs from five chemoresistant and five chemosensitive tumors. p values for the top 15 Hallmark terms enriched in CAFs from chemoresistant cases were determined by Student’s t test. ∗∗p < 0.01.
(C) Dot plot of biological GO terms upregulated in CAFs from chemoresistant (OCC-R) and chemosensitive (OCC-S) cases.
(D) Violin plots of the signature scores for the indicated CAFs from chemoresistant and chemosensitive cases.
(E) Volcano plots showing preferential induction of myCAF signature genes in CAFs from chemoresistant cases. Average expression values for the indicated CAF signature genes22 expressed by CAFs from chemoresistant and chemosensitive cases were calculated, and the relative ratios are shown. The horizontal and vertical axes represent the log10 values of fold changes and p values, respectively. Red dots, myCAF signature genes; yellow dots, iCAF signature genes; green dots: apCAF signature genes; black dots, panCAF signature genes. A list of the signature genes is presented in Table S3.
(F) Kaplan-Meier plots of OCCC (stages I–IV, n = 86). The patients were stratified into 4 groups: HIF-1αlow/FAP-αlow (n = 49), HIF-1αhigh/FAP-αlow (n = 11), HIF-1αlow/FAP-αhigh (n = 18), and HIF-1αhigh/FAP-αhigh (n = 8). Kaplan-Meier curves of progression-free survival and overall survival in each group are shown.
(G and H) Association of HIF-1α and FAP-α expression with poor prognosis. Association of the indicated parameters with progression-free survival or overall survival was evaluated by univariate (G) and multivariate (H) analyses (86 cases of OCCC). Hazard ratios (HRs), 95% confidence intervals, and p values were calculated with Cox’s proportional hazards regression model. ∗∗∗p < 0.001.