Claudin 18.2 is a potential therapeutic target for zolbetuximab in pancreatic ductal adenocarcinoma

Figure 1 Online analysis of gene expression of claudin 18 and its effected survival in pancreatic cancer using the database. A: Analysis of claudin18 expression in normal pancreatic tissue and pancreatic cancer using the TNMplot.com (https://tnmplot.com/analysis/) based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEX), and Gene Expression Omnibus (GEO) databases; B: Analysis of claudin18 expression in normal pancreatic tissue and pancreatic cancer using Xena (http://xena.ucsc.edu/compare-tissue/) based on TCGA and GTEX databases; C: Assessment of the claudin18 effect on survival in pancreatic cancer using KM plotter (https://kmplot.com/analysis/) based on GEO, European Genome-phenome Archive, and TCGA databases. HR: Hazard ratio.

Figure 2 Expression of claudin 18. 2 in primary pancreatic ductal adenocarcinoma. A: Examples of claudin 18.2 (CLDN18.2)-positive pancreatic ductal adenocarcinoma tissues with 0/none, 1+/weak, 2+/intermediate, and 3+/ strong staining intensity. Scale bar 100 μm; B: Overall expression intensity of claudin 18.2. Eighty-eight (94.6%) primary pancreatic ductal adenocarcinoma tissues showed positivity for CLDN18.2 expression. In the positive cases, most showed compositive immunohistochemistry (IHC)-intensity. Fifty (56.8%) cases were scored up to IHC 3+, 86 (97.7%) cases were scored up to but no higher than IHC 2+, and 77 (87.5%) cases were no higher than IHC 1+; C: Histoscore (H-Score) distribution in the study. Minimum H-Score was 0; Maximum H-score was 292. Median H-score of positive tumors was 150.

Figure 3 Claudin 18. 2 and survival. A: There was no significant correlation between tumor-specific survival and claudin 18.2 expression in tumor cells (41 vs 39 patients; median survival 13 mo vs 11 mo; P = 0.176); B: 20 vs 15 patients in stage I disease with median survival 24 mo vs 14 mo (P = 0.666); C: 12 vs 8 patients in stage II disease with median survival 9 mo vs 16 mo (P = 0.480); D: 4 vs 8 patients in stage III disease with median survival 15 mo vs 8 mo (P = 0.012); E: 5 vs 8 patients in stage IV disease with median survival 7 mo vs 3 mo (P = 0.009); F: 36 vs 31 patients in M0 disease with median survival 15 mo vs 13 mo (P = 0.351); G: 5 vs 8 patients in M1 disease with median survival 7 mo vs 4 mo (P = 0.024); H: 32 vs 18 patients in N0 disease with median survival 14 mo vs 13 mo (P = 0.825); I: 9 vs 21 patients in N1/N2 disease with median survival 11 mo vs 9 mo (P = 0.920). P values were obtained via log-rank-test. AJCC: American Joint Committee on Cancer; H-score: Histoscore.