Abstract 4582: Molecular and clinical characterization of claudin-18 expression in pancreatic cancer

Abstract Background: Claudin-18 (CLDN18) is a major component of tight junctions located on the cell membrane surface. CLDN18.1 and CLDN18.2 are specifically expressed in normal lung tissues and gastric mucosa, respectively. However, CNDN18.2 is known to be frequently expressed in gastric cancer, and also overexpressed in pancreatic cancer (PC) in 30-60% of cases. Clinical features of PC due to CLDN18 expression have been reported in a limited number of cases, and molecular features remain unknown. Here, we evaluated molecular and clinical characterization of CLDN18expression in advanced PC. Methods: This study used data from the MONSTAR-SCREEN-2 study, a nationwide molecular profiling project targeting solid tumors. Patients with advanced PC who received first-line systemic therapy and underwent tissue whole exome/transcriptome sequencing by Caris Life Sciences (Phoenix, AZ, USA) were included. Transcripts per million (TPM) for CLDN18 expression were categorized into high and low groups based on the median value. The clinical and molecular characteristics of these groups were compared. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment studies were carried out in R language using the programs clusterProfiler, enrichplot, and ggplot2. Differentially expressed genes identified based on log2 fold change greater than 1 and p-values less than 0.05 were used for pathway analysis. Only results with p-values and q-values no more than 0.05 were deemed significantly enriched. Results: A total of 104 patients were enrolled in the study. In the CLDN18-high and -low groups, the median age was 69 years/67.5 years; female was 57.7%/34.6%; tumor stage was recurrence 51.9%/30.8%, locally advanced 7.7%/9.6%, and metastatic 40.4%/59.6%; metastatic site was liver 48.1%/61.5%, lymph node 9.6%/11.5%, lung 17.3%/11.5%, and peritoneum 19.2%/9.6%; treatment regimens were FOLFIRINOX 21.2%/36.5% and gemcitabine + nab-paclitaxel 63.5%/51.9%, respectively. Objective response rate was 17.3%/19.2%, and disease control rate was 75.0%/63.5% (P = 0.29). The median overall survival was 16.5 and 18.7 months; hazard ratio (HR) 0.9 (95% confidence interval [CI] 0.5-1.7); P = 0.81. The median progression free survival was 7.3 and 5.3 months; HR 1.3 (95%CI 0.8-2.1); P = 0.28. The frequent gene alterations were KRAS, TP53, SMAD4, and CDKN2A, regardless of CLDN18 high and low groups. Gene expression such as GATA6 and CTSE, known as the characteristics of the classical type of Moffitt's classification, was significantly higher in CLDN18-high group, and gene expression such as S100A2 and KRT6A, known as the characteristics of the basal-like type, was significantly higher in CLDN18-low group. Conclusion: There was no significant difference in treatment efficacy and prognosis of systemic therapy between the CLDN18-high and -low groups. CLDN-high and -low were associated with known classical and basal-like molecular profiles. Citation Format: Tomoyuki Satake, Taro Shibuki, Chigusa Morizane, Makoto Ueno, Shogen Boku, Rie Sugimoto, Satoshi Shimizu, Yasuyuki Kawamoto, Yosuke Horita, Nobuhisa Matsuhashi, Shinji Itoh, Naohiro Okano, Takashi Ohta, Koushiro Ohtsubo, Tadayoshi Hashimoto, Takao Fujisawa, Mitsuho Imai, Yoshiaki Nakamura, Hideaki Bando, Takayuki Yoshino, Masafumi Ikeda. Molecular and clinical characterization of claudin-18 expression in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4582.