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Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

Low Expression of GRIM-19 Correlates with Poor Prognosis in Patients with Upper Urinary Tract Urothelial Carcinoma

In Press, (this is not the final "Version of Record"). Available online 05 June, 2024
Author(s): Feng Tian, Long Lv, Zonglin Liu, Sheng Guan, Fengze Jiang, Qi Wang, Dhan V Kalvakolanu, Sixiong Jiang and Weibing Sun*
Published on: 05 June, 2024

DOI: 10.2174/0115680096299093240516163839

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Purpose: 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.

Materials and Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Biomarker, gene associated with retinoid-interferon induced mortality-19, immunohistochemistry, prognosis, upper urinary tract urothelial carcinoma.

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