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. 2024 Apr 25;5(5):101532. doi: 10.1016/j.xcrm.2024.101532

Figure 3.

Figure 3

HIF-1α-positive chemoresistant cells reside near CAFs in chemoresistant OCCC

(A) Far left: H&E staining of OCC-R2 tissue sections. Right: Visium spatial transcriptomics (ST) spots on H&E-stained sections were overlaid with spatial feature plots of ovarian cancer cell markers (EPCAM, PAX8, and KRT7), CAF markers (COL1A1, COL1A2, DCN, and VIM), endothelial cell (TEC) markers (VWF, CDH5, and PECAM1), or an immune cell marker (PTPRC).

(B) UMAP plots of the Visium ST spots shown in (A). ST spots were classified into three clusters by unsupervised clustering and are denoted by different colors.

(C) Dot plots showing average expression of CAF markers and ovarian cancer cell markers by the indicated clusters. Three clusters shown in (B) were designated as cancer-dominated spots, CAF-dominated spots, and mixed spots, based upon expression of these markers.

(D) Spatial presentation of the three cluster in OCC-R2 tissue sections. Tissue localization of the clustered ST spots was visualized and is denoted by the indicated colors.

(E) Spatial feature plots of the prediction scores for the indicated cancer subpopulations (Cancer #1–5) in OCC-R2 tissue sections.

(F) Top: UMAP feature plots of ST spots of OCC-R2. Prediction scores for the indicated cancer subpopulations are shown in red. Bottom: violin plots of the prediction scores for the cancer subpopulations shown in the top columns. ST spots were classified into three groups as shown in (D), and the prediction scores for each group are presented.

(G) Violin plots showing the average expression values for the signature genes expressed by the indicated cancer subpopulations (Cancer #1–5) in ST spots of OCC-R2 and OCC-S3. In the boxplots inside the violin plots, the top and bottom bars of the boxes represent the 25th and 75th percentile, respectively, and the horizontal bars within the box indicate the median value.

(H) Representative magnified images of HIF-1α(+) cancer cells near α-SMA(+) CAFs in a chemoresistant tumor (OCC-R3). Scale bar, 100 μm.

(I) Nearest-neighbor analysis of the image shown in (H).

(J) Boxplot showing the average distance from PAX8(+)/HIF-1α(+) cells or PAX8(+)/HIF-1α(−) cells to the closest α-SMA(+) cell, calculated using the image shown in (H). ∗∗∗p < 0.001. p values were determined by Student’s t test.