Abstract 1477: TICRR is a prognosis biomarker associated with RNA epigenetic modification, DDR pathway, and RNA metabolism of lung adenocarcinoma

Abstract

Abstract Background: TOPBP1 interacting checkpoint and replication regulator (TICRR), a hub gene of the Cdk2-mediated initiation step of DNA replication, has been identified as a prognostic biomarker in papillary renal cell carcinoma (PRCC). Nevertheless, there are few studies on the comprehensive analysis between mRNA expression of TICRR and lung adenocarcinoma (LUAD). Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database of LUAD were acquired to analyze the mRNA expression between tumor and normal tissues, survival prognosis, and clinicopathology characters. The GO, KEGG, and gene set enrichment analysis (GSEA) were performed using the R package. The correlation of TICRR with immune cell infiltration, RNA epigenetic modification, DDR pathway, and RNA metabolism of LUAD were further explored using TCGA and GEO database. Results: TICRR was confirmed significantly upregulated in several cancers, like LUAD, Lung squamous cell carcinoma (LUSC), Uterine Corpus Endometrial Carcinoma (UCEC), except for Prostate adenocarcinoma (PRAD), Thyroid carcinoma (THCA), which was downregulated in tumor tissues. Cox analysis indicated the overexpression of TICRR was related to poor survival in several cancers. The KEGG enrichment showed TICRR expression positively related to cell cycle, homologous recombination, mismatch repair, DNA replication, and cysteine metabolism in LUAD. Pathway enrichment showed a close relationship with spliceosome, oxidative phosphorylation, and ubiquitin-mediated proteolysis. Immune infiltration analysis revealed TICRR expression was negatively correlated with B cell expression, immune score, stromal score, and immunostimulators like IL2 (P<0.001), and positively correlated with neutrophil cell expression, immune inhibitors like PD-L1 and CTLA4. Interestingly, high mRNA expression of TICRR correlates with DDR pathway signature (37 genes), 37 m6A/m5C regulated genes, and some metabolism-regulated genes. Single-cell analysis of six LUAD samples showed that TICRR was significantly enriched in macrophage and T cells. Conclusions: TICRR has been identified to be a prognosis biomarker in LUAD, which is involved in immune activation, pathway transportation, RNA modification, and tumor energy metabolism. TICRR can be used as a promising therapeutic target and prognosis indicator for LUAD. Citation Format: Xunbo Zheng, Jun Guan, Chenteng Chen, Li Han, Hanxing Huang. TICRR is a prognosis biomarker associated with RNA epigenetic modification, DDR pathway, and RNA metabolism of lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1477.