Ubiquitin-specific protease 35 (USP35) has gained attention as a regulator in cancer progression. However, its specific role in kidney clear cell carcinoma (KIRC) remains unclear. USP35 expression in KIRC tumor and normal tissues was evaluated using TCGA data. Correlations between USP35 expression, clinical parameters, and survival outcomes were examined. Functional enrichment analyses were performed to explore the pathways associated with USP35 expression. Immune-related analyses were conducted to assess the effect of USP35 on immune cell recruitment and neoantigen presentation. Drug sensitivity analyses were used to identify potential therapeutic agents targeting USP35. USP35 was significantly overexpressed in KIRC tumor tissues compared to normal tissues, and its high expression correlated with advanced disease stages and poor survival outcomes. Gene set enrichment analysis revealed that high USP35 expression was associated with oncogenic pathways, including glycerophospholipid and linoleic acid metabolism, while low expression linked to nitrogen and purine metabolism. USP35 also modulated immune responses, affecting immune cell recruitment and neoantigen presentation, suggesting a role in immune evasion. Drug sensitivity analysis showed that high USP35 expression correlated with increased sensitivity to paclitaxel, bosutinib, and lapatinib. In vitro knockdown of USP35 significantly reduced KIRC cell proliferation, migration, and epithelial-mesenchymal transition (EMT), further supporting its role in tumor progression. USP35 is overexpressed in KIRC and associated with poor prognosis, likely promoting tumor progression through oncogenic pathways and immune modulation. Its correlation with drug sensitivity positions USP35 as a potential therapeutic target, warranting further investigation into its mechanistic functions and therapeutic applications.

Background: In non-metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC), traditional prognostic factors, such as pN staging, often fail to distinguish patient outcomes effectively. Methods: This retrospective study included a cohort of 792 dMMR CRC patients who underwent surgical treatment without neoadjuvant chemoradiotherapy or immunotherapy. Traditional prognostic factors were compared with lymph node-based models (NLN, LNR, LOODS) for their ability to predict overall survival (OS) and disease-free survival (DFS). Results: The study demonstrated that traditional factors, such as histologic type, differentiation, and vascular invasion, had limited predictive value in dMMR CRC. Furthermore, the pN stage failed to effectively distinguish between pN1 and pN2 for both OS (p = 0.219) and DFS (p = 0.095). Conversely, LOODS demonstrated superior performance over traditional pN staging in predicting both OS and DFS (p < 0.001). A prognostic model combining LOODS with age exhibited superior predictive performance compared with the traditional TN staging system. Conclusions: LOODS was identified as a more effective independent prognostic factor compared with traditional pN staging, enabling more precise stratification of pN+ patients in non-metastatic dMMR CRC, highlighting its potential utility in guiding postoperative treatment and optimizing therapeutic strategies.