AUTHOR=Xia Shuang , Lin Yan , Lin Jiaqiong , Li Xiaoyong , Tan Xuexian , Huang Zena 

TITLE=Increased Expression of TICRR Predicts Poor Clinical Outcomes: A Potential Therapeutic Target for Papillary Renal Cell Carcinoma

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.605378

DOI=10.3389/fgene.2020.605378

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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 (<italic>TICRR</italic>) is a DNA replication initiation regulator upregulated in various cancers. We aimed to evaluate the role of <italic>TICRR</italic> in PRCC tumorigenesis and prognosis.</p><p><bold>Methods:</bold> Based on the Kidney Renal Papillary cell carcinoma Project (KIRP) on The Cancer Genome Atlas (TCGA) database, we determined the expression of <italic>TICRR</italic> using the Wilcoxon rank sum test. The biological functions of <italic>TICRR</italic> were evaluated using the Metascape database and Gene Set Enrichment Analysis (GSEA). The association between <italic>TICRR</italic> and immune cell infiltration was investigated by single sample GSEA. Logistic analysis was applied to study the correlation between <italic>TICRR</italic> expression and clinicopathological characteristics. Finally, Cox regression analysis, Kaplan–Meier analysis, and nomograms were used to determine the predictive value of <italic>TICRR</italic> on clinical outcomes in PRCC patients.</p><p><bold>Results:</bold><italic>TICRR</italic> expression was significantly elevated in PRCC tumors (<italic>P</italic> &lt; 0.001). Functional annotation indicated enrichment with negative regulation of cell division, cell cycle, and corresponding pathways in the high <italic>TICRR</italic> expression phenotype. High <italic>TICRR</italic> expression in PRCC was associated with female sex, younger age, and worse clinical stages. Cox regression analysis revealed that <italic>TICRR</italic> was a risk factor for overall survival [hazard ratio (HR): 2.80, <italic>P</italic> = 0.002], progression-free interval (HR: 2.86, <italic>P</italic> &lt; 0.001), and disease-specific survival (HR: 7.03, <italic>P</italic> &lt; 0.001), especially in patients with male sex, age below 60 years, clinical stages II–IV and clinical T stage T1–T2.</p><p><bold>Conclusion:</bold> Increased <italic>TICRR</italic> expression in PRCC might play a role in tumorigenesis by regulating the cell cycle and has prognostic value for clinical outcomes.</p>