Key Molecules in Bladder Cancer Affect Patient Prognosis and Immunotherapy Efficacy: Further Exploration for <i>CNTN1</i> and <i>EMP1</i>.

Abstract

Immunotherapy has been widely used in bladder cancer (BCa) in recent years and has significantly improved the prognosis of patients with BCa. However, further identification of immunotherapy-sensitive individuals to improve the efficacy of immunotherapy remains an important unmet need. The key genes were screened and identified from Gene Expression Omnibus database and The Cancer Genome Atlas database to construct the risk prediction function (risk scores). Real-time polymerase chain reaction, immunohistochemistry, and IMvigor210 data sets were used to verify the roles of key molecules and efficacy of risk scores. The biologic function of <i>CNTN1</i> and <i>EMP1</i> was further explored through cell proliferation experiments. Five key genes, <i>CNTN1</i>, <i>MAP1A</i>, <i>EMP1</i>, <i>MFAP5</i>, and <i>PTGIS</i>, which were significantly related to the prognosis and immune checkpoint molecules of patients, were screened out. <i>CNTN1</i> and <i>EMP1</i> were further experimentally confirmed for their significant tumor-promoting effects. Besides, the constructed risk scores on the basis of these five key genes can accurately predict the prognosis and immunotherapy efficacy of patients with BCa. Interestingly, the high-risk patients identified by the risk scores have significantly worse prognosis and immunotherapy effects than low-risk patients. The key genes we screened can affect the prognosis of BCa, tumor microenvironment immune infiltration, and the efficacy of immunotherapy. The risk scores tool we constructed will contribute to the development of individualized treatment for BCa.