Integrative Analysis Reveals Across-Cancer Expression Patterns and Clinical Relevance of Ribonucleotide Reductase in Human Cancers

Yongfeng Ding; Tingting Zhong; Min Wang; Xueping Xiang; Guoping Ren; Zhongjuan Jia; Qinghui Lin; Qian Liu; Jingwen Dong; Linrong Li; Xiawei Li; Haiping Jiang; Lijun Zhu; Haoran Li; Dejun Shen; Lisong Teng; Chen Li; Jimin Shao

doi:10.3389/fonc.2019.00956

Integrative Analysis Reveals Across-Cancer Expression Patterns and Clinical Relevance of Ribonucleotide Reductase in Human Cancers

Front Oncol. 2019 Oct 4:9:956. doi: 10.3389/fonc.2019.00956. eCollection 2019.

Authors

Yongfeng Ding^{1

2

3}, Tingting Zhong^{1

2

4}, Min Wang⁵, Xueping Xiang^{1

2}, Guoping Ren³, Zhongjuan Jia¹, Qinghui Lin¹, Qian Liu¹, Jingwen Dong¹, Linrong Li¹, Xiawei Li¹, Haiping Jiang³, Lijun Zhu³, Haoran Li⁶, Dejun Shen⁷, Lisong Teng³, Chen Li⁵, Jimin Shao^{1

2}

Affiliations

¹ Department of Pathology & Pathophysiology, and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Key Laboratory of Disease Proteomics of Zhejiang Province, Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Research Center for Air Pollution and Health, Zhejiang University School of Medicine, Hangzhou, China.
³ Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Department of Medical Oncology, Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁵ Department of Human Genetics, Zhejiang University School of Medicine, Hangzhou, China.
⁶ Discovery Biochemistry, Kymera Therapeutics, Cambridge, MA, United States.
⁷ Southern California Permanente Medical Group, Department of Pathology, Downey Medical Center, Downey, CA, United States.

Abstract

Mining cancer-omics databases deepens our understanding of cancer biology and can lead to potential breakthroughs in cancer treatment. Here, we propose an integrative analytical approach to reveal across-cancer expression patterns and identify potential clinical impacts for genes of interest from five representative public databases. Using ribonucleotide reductase (RR), a key enzyme in DNA synthesis and cancer-therapeutic targeting, as an example, we characterized the mRNA expression profiles and inter-component associations of three RR subunit genes and assess their differing pathological and prognostic significance across over 30-types of cancers and their related subtypes. Findings were validated by immunohistochemistry with clinical tissue samples (n = 211) collected from multiple cancer centers in China and with clinical follow-up. Underlying mechanisms were further explored and discussed using co-expression gene network analyses. This framework represents a simple, efficient, accurate, and comprehensive approach for cancer-omics resource analysis and underlines the necessity to separate the tumors by their histological or pathological subtypes during the clinical evaluation of molecular biomarkers.

Keywords: cancer-omics; clinical relevance; expression characteristics; gene networks; integrative analysis; ribonucleotide reductase.