Cell Genomics (Jan 2023)
Multi-omics characterization of silent and productive HPV integration in cervical cancer
- Junpeng Fan,
- Yu Fu,
- Wenju Peng,
- Xiong Li,
- Yuanming Shen,
- Ensong Guo,
- Funian Lu,
- Shengtao Zhou,
- Si Liu,
- Bin Yang,
- Xu Qin,
- Dianxing Hu,
- Rourou Xiao,
- Xi Li,
- Siqi Yang,
- Cunzhong Yuan,
- Yao Shu,
- He Huang,
- Ting Wan,
- Yanan Pi,
- Shuxiang Wang,
- Wenjuan Chen,
- Haixia Wang,
- Lin Zhong,
- Li Yuan,
- Baogang Wen,
- Beihua Kong,
- Gordon B. Mills,
- Dongling Zou,
- Bairong Xia,
- Kun Song,
- Gang Chen,
- Ding Ma,
- Chaoyang Sun
Affiliations
- Junpeng Fan
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Yu Fu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Wenju Peng
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Xiong Li
- Department of Gynecology & Obstetrics, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Yuanming Shen
- Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
- Ensong Guo
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Funian Lu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Shengtao Zhou
- 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
- Si Liu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Bin Yang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Xu Qin
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Dianxing Hu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Rourou Xiao
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Xi Li
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Siqi Yang
- Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
- Cunzhong Yuan
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250000, China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Jinan 250000, China; Division of Gynecology Oncology, Qilu Hospital of Shandong University, Jinan 250000, China
- Yao Shu
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250000, China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Jinan 250000, China; Division of Gynecology Oncology, Qilu Hospital of Shandong University, Jinan 250000, China
- He Huang
- Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510000, China
- Ting Wan
- Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510000, China
- Yanan Pi
- 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
- Shuxiang Wang
- 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
- Wenjuan Chen
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 404100, China
- Haixia Wang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 404100, China
- Lin Zhong
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 404100, China
- Li Yuan
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 404100, China
- Baogang Wen
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 404100, China
- Beihua Kong
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250000, China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Jinan 250000, China; Division of Gynecology Oncology, Qilu Hospital of Shandong University, Jinan 250000, China
- Gordon B. Mills
- Department of Cell, Developmental, and Cancer Biology, Oregon Health and Sciences University, Portland, OR 97201, USA; Knight Cancer Institute, Portland, OR 97201, USA
- Dongling Zou
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 404100, China; Corresponding author
- Bairong Xia
- 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; Corresponding author
- Kun Song
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250000, China; Gynecology Oncology Key Laboratory, Qilu Hospital of Shandong University, Jinan 250000, China; Division of Gynecology Oncology, Qilu Hospital of Shandong University, Jinan 250000, China; Corresponding author
- Gang Chen
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; Corresponding author
- Ding Ma
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; Corresponding author
- Chaoyang Sun
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; Corresponding author
- Journal volume & issue
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Vol. 3,
no. 1
p. 100211
Abstract
Summary: 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.
