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Multi-omics characterization of silent and productive HPV integration in cervical cancer

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机构： [1]Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China [2]Department of Gynecology & Obstetrics, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China [3]Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China [4]Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610000, China [5]Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250000, China [6]Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Jinan 250000, China [7]Division of Gynecology Oncology, Qilu Hospital of Shandong University, Jinan 250000, China [8]Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510000, China [9]Department of Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, China [10]Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 404100, China [11]Department of Cell, Developmental, and Cancer Biology, Oregon Health and Sciences University, Portland, OR 97201, USA [12]Knight Cancer Institute, Portland, OR 97201, USA

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Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV integration sites were nonrandomly distributed across both viral and host genomes, suggesting that productive integration sites are under selection and likely to contribute to CC pathophysiology. Furthermore, using large-scale, multi-omics (clinical, genomic, transcriptional, proteomic, phosphoproteomic, and single-cell) data, we demonstrate that tumors with productive HPV integration are associated with higher E6/E7 proteins and enhanced tumor aggressiveness and immunoevasion. Importantly, productive HPV integration increases from carcinoma in situ to advanced disease. This study improves our understanding of the functional consequences of HPV fusion transcripts on the biology and pathophysiology of HPV-driven CCs, suggesting that productive HPV integration should be evaluated as an indicator of high risk for progression to aggressive cancers.© 2022 The Authors.

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出版当年[2023]版：

Q1 CELL BIOLOGY Q1 GENETICS & HEREDITY

最新[2023]版：

Q1 CELL BIOLOGY Q1 GENETICS & HEREDITY

影响因子： 11.1 最新[2023版] 0 最新五年平均 11.1 出版当年[2023版] 0 出版当年五年平均 0 出版前一年[2022版]

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第一作者机构： [1]Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China

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通讯机构： [5]Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250000, China [6]Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Jinan 250000, China [7]Division of Gynecology Oncology, Qilu Hospital of Shandong University, Jinan 250000, China

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