Affiliations: [a] Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China | [b] Biotecan Medical Diagnostics Co., Ltd, Shanghai 201204, China | [c] Department of Gynecology and Obstetrics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China | [d] School of Public Health, Fujian Medical University, Fuzhou, Fujian 350004, China | [e] Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Public Health Research Center of Jiangnan University, Wuxi, Jiangsu 214064, China | [f] Shanghai Zhangjiang Institute of Medical Innovation, Shanghai 201204, China
Correspondence:
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Corresponding author: Zhishan Zhang, Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, No. 248 East Street, Quanzhou City, Fujian 362002, China. Tel/Fax: +86 595 22277352; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Abstract: BACKGROUND: Worldwide, cervical cancer is the fouth leading cause of deaths in gynecological oncology. Although the causes of cervical cancer have been extensively investigated, understanding of its exact pathogenesis remains incomplete. OBJECTIVE: This study aimed to identify alterations of genome and transcriptome of HPV associated cervical cancer pathogenesis using multi-omics approaches. METHODS: Cervical cancer and matched adjacent non-tumor specimens of one HPV16+ and two HPV- patients were sampled for whole-exome sequencing (WES) and RNA sequencing to characterize DNA mutations and gene expression profiles. WES and Affymetrix SNP 6.0 arrays data were analyzed from 6 HPV- and 93 HPV16+ cervical cancer patients in the cancer genome atlas (TCGA) database, as an independent validation group. RESULTS: WES identified 64 somatic mutation genes in tumors of 3 patients. HPV16+ tumor got fewer somatic mutated genes than HPV- tumors, which was validated by TCGA results. In this study, somatic mutated profile, CNV and gene expression heat map presented that HPV16+ tumors was distinct with HPV- tumors. The most significant altered pathways and GO terms were both related with cell cycle. Integrated analysis of multi-omics showed positive correlation between gene expression level and copy numbers. CONCLUSIONS: The results of this study provided novel insights into the pathogenesis of HPV associated cervical cancer.
