Abstract
Background: Papillary renal cell carcinoma (PRCC), although the second-most common type of renal cell carcinoma, still lacks specific biomarkers for diagnosis, treatment, and prognosis. TopBP1-interacting checkpoint and replication regulator (TICRR) is a DNA replication initiation regulator upregulated in various cancers. We aimed to evaluate the role of TICRR in PRCC tumorigenesis and prognosis.Methods: Based on the Kidney Renal Papillary cell carcinoma Project (KIRP) on The Cancer Genome Atlas (TCGA) database, we determined the expression of TICRR using the Wilcoxon rank sum test. The biological functions of TICRR were evaluated using the Metascape database and Gene Set Enrichment Analysis (GSEA). The association between TICRR and immune cell infiltration was investigated by single sample GSEA. Logistic analysis was applied to study the correlation between TICRR expression and clinicopathological characteristics. Finally, Cox regression analysis, Kaplan–Meier analysis, and nomograms were used to determine the predictive value of TICRR on clinical outcomes in PRCC patients.Results: TICRR expression was significantly elevated in PRCC tumors (P < 0.001). Functional annotation indicated enrichment with negative regulation of cell division, cell cycle, and corresponding pathways in the high TICRR expression phenotype. High TICRR expression in PRCC was associated with female sex, younger age, and worse clinical stages. Cox regression analysis revealed that TICRR was a risk factor for overall survival [hazard ratio (HR): 2.80, P = 0.002], progression-free interval (HR: 2.86, P < 0.001), and disease-specific survival (HR: 7.03, P < 0.001), especially in patients with male sex, age below 60 years, clinical stages II–IV and clinical T stage T1–T2.Conclusion: Increased TICRR expression in PRCC might play a role in tumorigenesis by regulating the cell cycle and has prognostic value for clinical outcomes.
Highlights
Renal cell carcinoma (RCC) is a life-threatening cancer worldwide, ranking sixth among the most commonly diagnosed cancers in men and 10th in women (Siegel et al, 2018)
High TopBP1-interacting checkpoint and replication regulator (TICRR) expression in Papillary RCC (PRCC) was associated with female sex, younger age, and worse clinical stages
Increased TICRR expression in PRCC might play a role in tumorigenesis by regulating the cell cycle and has prognostic value for clinical outcomes
Summary
Renal cell carcinoma (RCC) is a life-threatening cancer worldwide, ranking sixth among the most commonly diagnosed cancers in men and 10th in women (Siegel et al, 2018). Papillary RCC (PRCC) is the second most common type of RCC, accounting for nearly 18% of RCC (Srigley et al, 2013). Recent studies have introduced several novel biomarkers for RCC diagnosis and prognosis, such as urine aquaporin-1 and perilipin-2 (Farber et al, 2017; Cao et al, 2018; Song et al, 2019) These studies were mostly carried out in patients with rough RCC or clear cell RCC, lacking specific result for PRCC. Several mutated genes were proved to be associated with PRCC diagnosis and treatment, including MET, NF2, SETD2, and Nrf pathway genes. Papillary renal cell carcinoma (PRCC), the second-most common type of renal cell carcinoma, still lacks specific biomarkers for diagnosis, treatment, and prognosis. We aimed to evaluate the role of TICRR in PRCC tumorigenesis and prognosis
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