Landscape Analysis of CLDN18 Expression and Isoform Distribution in Solid Tumors: Insights From MONSTAR-SCREEN-2 Study.
Hashimoto T., Iida N., Nakamura Y., Nonomura N., Morizane C., Iwata H., Okano S., Yamagami W., Yamazaki N., Kadowaki S., Ueno M., Boku S., Oki E., Komatsu Y., Yuki S., Makiyama A., Ogata T., Takahashi N., Okano N., Nishina T., Sakamoto N., Kuwata T., Yamashita R., Shibuki T., Imai M., Fujisawa T., Bando H., Shitara K., Yoshino T.
Claudin 18.2 (CLDN18.2), a tight junction protein isoform, is an emerging therapeutic target in oncology. CLDN18 is well-characterized in gastric cancer, but its pan-cancer expression profiles and isoform distributions are poorly documented. In the present study, we analyzed CLDN18 expression in patients with solid tumors enrolled in the MONSTAR-SCREEN-2 study using immunohistochemistry (IHC, n = 349) and whole-transcriptome sequencing (WTS, n = 2191). A splice junction analysis algorithm characterized isoform distribution patterns in WTS data and evaluated temporal changes using paired pre- and postchemotherapy specimens. IHC detected CLDN18.2 (≥ 40% of tumor cells showing any staining intensity) in 16.3% of patients, with highest prevalence in gastric (54.5%), biliary tract (21.7%), pancreatic (20.7%), and small intestinal (18.2%) cancers. WTS and IHC findings were significantly correlated (p