Fig. 1 | Signal Transduction and Targeted Therapy

Fig. 1

From: The dysadherin/carbonic anhydrase 9 axis shapes an acidic tumor microenvironment to promote colorectal cancer progression

Fig. 1The alternative text for this image may have been generated using AI.

An acidic TME is positively associated with dysadherin expression and contributes to CRC progression. a A list of DEGs in tumor tissue compared with normal tissue was obtained from the GEO database (GSE106582) (p < 0.001). The gene list was analyzed via a curated gene set and the GO gene set of GSEA to determine the associated gene signatures. b A UMAP plot of the epithelial cell cluster from CRC patients (GSE144735) was generated. Trajectory analysis was performed via Monocle2, which orders cells on the basis of their malignant progression states. The expression patterns of malignancy-associated and tumor-acidosis–related genes were examined along the inferred trajectory. c Heatmap comparing the relative expression levels of malignancy and tumor-acidosis-related genes in CRC patient tissues (n = 4/group). d IF analysis of dysadherin and LAMP2 expression in CRC patient tissues, with samples grouped according to tumor stage. (S1, n = 45; S2, n = 62; S3, n = 61; total, n = 168). Graphs showing the intensity and correlation of dysadherin and LAMP2 protein expression. e Kaplan–Meier survival analysis was performed on patients with stage II and III CRC. Patients were divided into three groups on the basis of dysadherin and LAMP2 expression: high (n = 52), low (n = 45), and others (n = 26), for a total of 123 patients. Statistical significance was determined by log-rank tests. f IF analysis of dysadherin in the intestines of 24-week-old ApcMin/+ mice with or without dysadherin (Fxyd5) KO (n = 5/group). The upper violin plot shows the number of visible tumors per mouse. The lower violin plot shows the tumor load, which is calculated as a weighted sum that incorporates both tumor number and size: (small tumors × 1) + (medium tumors × 2) + (large tumors × 3). g pHrodo and HPTS staining of mouse intestinal tumors (n = 5/group). The data are shown as the means ± SEMs. *, **, and *** denote p < 0.05, p < 0.01, and p < 0.001, respectively. Statistical significance was assessed via unpaired two-tailed Student’s t-tests for two-group comparisons and one-way ANOVA with Dunnett’s multiple comparison test for analyses involving three groups. Dys dysadherin, S1 stage 1, S2 stage 2, S3 stage 3

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