Abstract 3293: CADM1 is a serum marker for small-cell lung cancer associated with poor prognosis and metastasis

Abstract

Small-cell lung cancer (SCLC) is aggressive neuroendocrine cancer that accounts for approximately 15% of lung cancer. Although chemotherapy is effective for SCLC, resistant tumors develop rapidly; therefore, early detection in the initial screening and after chemotherapy is one of the critical issues in controlling SCLC progression. For this purpose, neuron-specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP) are used as tumor markers for SCLC but are not sensitive enough, especially in the early stages. Previously we found that Cell adhesion molecule 1 (CADM1) is highly expressed in SCLC, and an SCLC-specific splicing variant, CADM1v8/9, is selectively cleaved by ADAM17 protease to release the extracellular fragments. Here, we report that soluble CADM1v8/9 fragments (sCADM1v8/9) can be a serum marker of SCLC associated with poor prognosis and metastasis. Immunohistochemical analysis showed that the expression of CADM1 was observed in 83% of the resected SCLC cases and strongly correlated with that of INSM1, a marker of neuroendocrine differentiation. The high expression of CADM1 was associated with poor prognosis and nodal involvement, which was supported by experimental data showing that CADM1 promoted subcutaneous tumor growth and lymph node metastasis of SCLC cells in nude mice. Moreover, sCADM1v8/9 distinguished 47% of SCLC, including a significant portion of patients with limited disease SCLC, independent of and partly overlapped with the cases detected by ProGRP or NSE. Notably, a high amount of sCADM1v8/9 was observed in SCLC cases with liver metastasis or pleural effusion. Furthermore, serum levels of sCADM1v8/9 well reflected the change in tumor burden before and after chemotherapy. These findings indicate that detecting sCADM1v8/9 in sera would provide clinical benefits in diagnosis, follow-up, and metastasis prediction of SCLC cases. Citation Format: Takeshi Ito, Toko Funaki, Hiroko Iwanari, Goh Tanaka, Takahide Nagase, Takao Hamakubo, Yoshinori Murakami. CADM1 is a serum marker for small-cell lung cancer associated with poor prognosis and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3293.