Identifying ribonucleotide reductase subunit genes as potential lung adenocarcinomas biomarkers using integrated bioinformatics analysis

Jin Shang¹, Blessed Kondowe², Hui Zhang¹, and Xinming Xie³*

1. Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, PR China
2. Radiology Department, Mzuzu Central Hospital, Mzuzu, Malawi
3. Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, PR China

*Corresponding Author: Xinming Xie; E-mail: xiexinming1986@163.com

Abstract
Introduction
Dysregulation of ribonucleotide reductase (RR) subunit genes (RRM1, RRM2 and RRM2B) expression is reported to be involved in the occurrence of various human malignancies. However, the prognostic value of RR subunit genes expression in lung adenocarcinoma (LUAD) patients remains controversial.
Objective
This study aims to analyze the expression profiles, prognostic values, and immune infiltrating associations of RR subunit genes in LUAD to explore whether RR subunit gene expression has value in the prognosis of patients with lung adenocarcinoma (LUAD).
Methodology
We used multiple search engines to access multiple online bioinformatics databases, including Oncomine, TIMER, GEPIA, Kaplan–Meier Plotter, PrognoScan, the Human Protein Atlas, MD Anderson Cancer Center, UCSC Xena, cBioProtal, TCGA, GEO, DAVID, and STRING databases.
Results
The study found that RRM1 and RRM2 might be an attractive target for treating LUAD, while RRM2B were down-expressed in LUAD (P < 0.05). The study also found that high RRM1 or RRM2 expression, or low RRM2B expression suggested poor prognosis of LUAD patients in both TCGA and GEO databases (P < 0.05). Additionally, our results indicated that RR subunit genes expressions have different characteristics with immune infiltrating, RRM2B had a slight but significant positive correlation with almost every infiltrating immune cells except CD4+ T cells (all P < 0.05). Furthermore, by co-expression gene network analysis of RR subunit genes, we found that five new hub genes (PLK1, AURKA, CDCA8, TTK and CDC45) were significantly positively correlated with RRM1 and RRM2 expression whereas were negatively correlated with RRM2B expression, and these five hub genes were identified to be related with a poor prognosis in LUAD patients (P < 0.05).
Conclusion
The study findings demonstrate that RR subunit genes may be a prognostic marker and therapeutic target for LUAD patients.