NXPH4 Used as a New Prognostic and Immunotherapeutic Marker for Muscle-Invasive Bladder Cancer

Abstract

Background. One of the most common malignant tumors of the urinary system is muscle-invasive bladder cancer (MIBC). With the increased use of immunotherapy, its importance in the field of cancer is becoming abundantly evident. This study classifies MIBC according to GSVA score from the perspective of the GSEA immune gene set. Methods. This study integrated the sequencing and clinical data of MIBC patients in TCGA and GEO databases, then scored the data using the GSVA algorithm, the CNMF algorithm was implemented to divide the subtypes of GEO and TCGA datasets, respectively, and finally screened and determined the key pathways in combination with clinical data. Simultaneously, LASSO Cox regression model was constructed based on key pathway genes to assess the model’s predictive ability (ROC) and describe the immune landscape differences between high- and low-risk groups; key genes were further analyzed and verified in patient tissues. Results. 404 TCGA and 297 GEO datasets were divided into C1-3 groups (TCGA-C1:120/C2:152/C3:132; GEO- C1:112/C2:101/C3:84), of which TCGA-C2 ( $n=152$ ) subtype and GEO-C1 ( $n=112$ ) subtype had the worst prognosis. LASSO Cox regression model with ROC ( $\text{train}\text{set}=0.718$ , $\text{test}\text{set}=0.667$ ) could be constructed. When combined with the Cancer Immunome Atlas database, it was found that patients with high-risk scores were more sensitive to PD-1 inhibitor and PD-1 inhibitor combined with CTLA-4. NXPH4, as a key gene, plays a role in MIBC with tissue validation results show that nxph4 is highly expressed in tumor. Conclusion. The immune gene score of MIBC data in TCGA and GEO databases was successfully evaluated using GSVA in this research. The lasso Cox expression model was successfully constructed by screening immune genes, the high-risk group had a worse prognosis and higher sensitivity to immunotherapy, PD-1 inhibitors or PD-1 combined with CTLA-4 inhibitors can be preferentially used in high-risk patients who are sensitive to immunotherapy, and NXPH4 may be a molecular target to adjust the effect of immunotherapy.