PTGER4 Governs Immune Evasion and Therapy Resistance in Kidney Cancer via Ribosome Biogenesis Dysregulation.

Kidney renal clear cell carcinoma (KIRC) is associated with abnormal ribosome production (RiboSis), but how this affects tumour growth and response to immunotherapy is still unclear. In this study, we analysed large-scale multi-omics data using machine learning. Using single-cell RNA sequencing and gene network analysis (hdWGCNA), we found a key RiboSis-related gene group. We then classified KIRC tumours into two subtypes based on RiboSis activity. Patients with subtype 1 lived significantly longer, and this group showed activation of tumour-promoting pathways. Using machine learning, we identified PTGER4 as a potential tumour suppressor. Higher PTGER4 levels were linked to better survival in multiple patient groups. Tumours with high PTGER4 also had stronger immune cell activity and higher levels of immunotherapy-related markers, suggesting they may respond better to immune-based treatments. PTGER4 also predicted better outcomes with certain chemotherapy drugs. Further analysis confirmed that PTGER4 is involved in immune-related pathways and is often reduced in tumours, supporting its role in slowing cancer progression. Lab experiments confirmed that PTGER4 helps block tumour growth. These findings suggest PTGER4 plays a central role in KIRC progression and treatment response. Targeting RiboSis-related mechanisms and PTGER4-related pathways could lead to better therapies for KIRC patients.