Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in oral squamous cell carcinoma

Yuancheng Li; Linnan Gong; Na Qin; Xiaoyu Wei; Limin Miao; Hua Yuan; Cheng Wang; Hongxia Ma

doi:10.1016/j.oraloncology.2021.105437

Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in oral squamous cell carcinoma

Oral Oncol. 2021 Oct:121:105437. doi: 10.1016/j.oraloncology.2021.105437. Epub 2021 Jul 13.

Authors

Yuancheng Li¹, Linnan Gong¹, Na Qin¹, Xiaoyu Wei¹, Limin Miao², Hua Yuan³, Cheng Wang⁴, Hongxia Ma⁵

Affiliations

¹ Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
² Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
³ Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
⁴ Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China. Electronic address: chengwang29@njmu.edu.cn.
⁵ Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. Electronic address: hongxiama@njmu.edu.cn.

PMID: 34265729
DOI: 10.1016/j.oraloncology.2021.105437

Abstract

Objective: CircRNAs are critical gene modulators in tumor initiation and progression. However, the expression pattern and molecular pathogenesis of circRNAs in oral squamous cell carcinoma (OSCC) are still poorly characterized.

Methods: RNA sequencing with CIRCexplorer2 pipeline was performed to identify circRNAs in 46 tumor-normal paired tissues from OSCC patients. Another set of 48 head and neck squamous cell carcinoma samples from the MiOncoCirc database were utilized as an independent validation.

Results: Of the 1276 identified high-confidence circRNAs, 154 were differentially expressed between tumor and normal tissues (log₂|Fold Change|≥1 and false discovery rate < 0.05). CircRNAs expression was globally down-regulated in tumors compared to normal tissues (P = 9.44 × 10^-14). Correlation analysis demonstrated that the global expression of circRNAs was positively related to tumor infiltrating lymphocyte (P = 1.10 × 10^-4) and stromal signature (P = 2.70 × 10^-3) whereas negatively associated with cell proliferation markers (P = 4.32 × 10^-2). CircRNAs-miRNAs-mRNAs regulatory network revealed 6574 interactions, and the target genes were enriched in extracellular matrix and immune-related pathways. Survival analysis were performed on target genes in immune-related pathways, and 20 genes were significantly associated with the prognostic status of OSCC in The Cancer Genome Atlas cohort. The risk model constructed with above 20 genes was associated with the prognosis status of OSCC (HR = 3.28, P = 5.06 × 10^-11), and the result was validated in an independent study (GSE41613) (HR = 2.06, P = 1.73 × 10^-2).

Conclusion: CircRNAs showed a global down-regulation pattern in OSCC tissues, and genes regulated by circRNAs primarily involved in immune and extracellular matrix pathways, which could also affect the OSCC prognosis, indicating that they may serve as potential prognostic biomarkers.

Keywords: Circular RNAs; Competing endogenous network; Oral squamous cell carcinoma; RNA sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gene Expression Profiling
Humans
MicroRNAs* / genetics
Mouth Neoplasms* / genetics
RNA, Circular / genetics*
RNA, Messenger / genetics
Squamous Cell Carcinoma of Head and Neck* / genetics

Substances

MicroRNAs
RNA, Circular
RNA, Messenger