Tian Feng, Lv Long, Liu Zonglin, Guan Sheng, Jiang Fengze, Wang Qi, Kalvakolanu Dhan V, Jiang Sixiong, Sun Weibing
Key Laboratory of Microenvironment Regulation and Immunotherapy of Urinary Tumors of Liaoning Province, Department of Urology, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, Liaoning, China.
Department of Urology, Anshan Tumor Hospital, Anshan, 114000, Liaoning, China.
Curr Cancer Drug Targets. 2025;25(4):401-411. doi: 10.2174/0115680096299093240516163839.
This study aimed to clarify the expression of a gene associated with Retinoid- Interferon-Induced Mortality-19 (GRIM-19) in Upper Urinary Tract Urothelial Carcinoma (UUTUC) and its prognostic significance for UUTUC patients.
Immunohistochemical (IHC) staining was used to determine the GRIM-19 expression in 70 paired samples. Progression-Free Survival (PFS) and Cancer-Specific Survival (CSS) were assessed using the Kaplan-Meier method. The independent prognostic factors for PFS and CSS were analyzed by multivariable Cox regression models.
IHC staining showed that GRIM-19 expression was significantly decreased in UUTUC, and its cellular location changed from being both cytoplasmic and nuclear to only cytoplasmic. Kaplan- Meier analysis revealed that the patients with tumors expressing low GRIM-19 had a significantly higher risk for tumor progression (P = 0.002) and cancer-specific mortality (P < 0.001) compared to those with high GRIM-19 levels. The Cox regression showed that both GRIM-19 expression (P = 0.025) and lymph node metastasis (LN) (P = 0.007) were independent predictors of progression in the muscle-invasive (MIC) subgroup. GRIM-19 expressions (entire cohort: P = 0.011; MIC subgroup: P = 0.025), LN (entire cohort: P = 0.019; MIC subgroup: P = 0.007), and progression (entire cohort: P < 0.001; MIC subgroup: P < 0.001) were independent predictors of cancer-specific survival.
Low expression of GRIM-19 in patients with UUTUC had significantly shorter PFS or CSS compared to those with high GRIM-19-expressing tumors. High GRIM-19 expression was also strongly associated with longer PFS in MIC patients. It indicates that GRIM-19 might serve as a promising prognostic biomarker for UUTUC patients.
本研究旨在阐明类视黄醇-干扰素诱导死亡率-19（GRIM-19）相关基因在上尿路尿路上皮癌（UUTUC）中的表达及其对UUTUC患者的预后意义。
采用免疫组织化学（IHC）染色法检测70对样本中的GRIM-19表达。采用Kaplan-Meier法评估无进展生存期（PFS）和癌症特异性生存期（CSS）。通过多变量Cox回归模型分析PFS和CSS的独立预后因素。
IHC染色显示，UUTUC中GRIM-19表达显著降低，其细胞定位从细胞质和细胞核均有变为仅在细胞质中。Kaplan-Meier分析显示，与GRIM-19高表达患者相比，GRIM-19低表达肿瘤患者的肿瘤进展风险显著更高（P = 0.002），癌症特异性死亡率也更高（P < 0.001）。Cox回归显示，GRIM-19表达（P = 0.025）和淋巴结转移（LN）（P = 0.007）均为肌层浸润性（MIC）亚组进展的独立预测因素。GRIM-19表达（整个队列：P = 0.011；MIC亚组：P = 0.025）、LN（整个队列：P = 0.019；MIC亚组：P = 0.007）和进展情况（整个队列：P < 0.001；MIC亚组：P < 0.001）是癌症特异性生存的独立预测因素。
与GRIM-19高表达肿瘤患者相比，UUTUC患者中GRIM-19低表达的患者PFS或CSS显著缩短。GRIM-19高表达也与MIC患者更长的PFS密切相关。这表明GRIM-19可能是UUTUC患者有前景的预后生物标志物。
