Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library

High‐grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with 5‐year survival rates below 40%. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients with advanced‐stage HGSOC unsuitable for primary debulking surgery (...

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Main Authors: Liujia Qian, Jianqing Zhu, Zhangzhi Xue, Tingting Gong, Nan Xiang, Liang Yue, Xue Cai, Wangang Gong, Junjian Wang, Rui Sun, Wenhao Jiang, Weigang Ge, He Wang, Zhiguo Zheng, Qijun Wu, Yi Zhu, Tiannan Guo
Format: Article
Language:English
Published: Wiley 2023-08-01
Series:Molecular Oncology
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Online Access:https://doi.org/10.1002/1878-0261.13410
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author Liujia Qian
Jianqing Zhu
Zhangzhi Xue
Tingting Gong
Nan Xiang
Liang Yue
Xue Cai
Wangang Gong
Junjian Wang
Rui Sun
Wenhao Jiang
Weigang Ge
He Wang
Zhiguo Zheng
Qijun Wu
Yi Zhu
Tiannan Guo
author_facet Liujia Qian
Jianqing Zhu
Zhangzhi Xue
Tingting Gong
Nan Xiang
Liang Yue
Xue Cai
Wangang Gong
Junjian Wang
Rui Sun
Wenhao Jiang
Weigang Ge
He Wang
Zhiguo Zheng
Qijun Wu
Yi Zhu
Tiannan Guo
author_sort Liujia Qian
collection DOAJ
description High‐grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with 5‐year survival rates below 40%. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients with advanced‐stage HGSOC unsuitable for primary debulking surgery (PDS). However, about 40% of patients receiving this treatment exhibited chemoresistance of uncertain molecular mechanisms and predictability. Here, we built a high‐quality ovary‐specific spectral library containing 130 735 peptides and 10 696 proteins on Orbitrap instruments. Compared to a published DIA pan‐human spectral library (DPHL), this spectral library provides 10% more ovary‐specific and 3% more ovary‐enriched proteins. This library was then applied to analyze data‐independent acquisition (DIA) data of tissue samples from an HGSOC cohort treated with NACT, leading to 10 070 quantified proteins, which is 9.73% more than that with DPHL. We further established a six‐protein classifier by parallel reaction monitoring (PRM) to effectively predict the resistance to additional chemotherapy after IDS (Log‐rank test, P = 0.002). The classifier was validated with 57 patients from an independent clinical center (P = 0.014). Thus, we have developed an ovary‐specific spectral library for targeted proteome analysis, and propose a six‐protein classifier that could potentially predict chemoresistance in HGSOC patients after NACT‐IDS treatment.
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spelling doaj.art-8619fcefd55247989b5c3a84bdf9c3e12023-08-03T16:44:14ZengWileyMolecular Oncology1574-78911878-02612023-08-011781567158010.1002/1878-0261.13410Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral libraryLiujia Qian0Jianqing Zhu1Zhangzhi Xue2Tingting Gong3Nan Xiang4Liang Yue5Xue Cai6Wangang Gong7Junjian Wang8Rui Sun9Wenhao Jiang10Weigang Ge11He Wang12Zhiguo Zheng13Qijun Wu14Yi Zhu15Tiannan Guo16School of Medicine Zhejiang University Hangzhou ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Hangzhou ChinaKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University Hangzhou ChinaDepartment of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University Hangzhou ChinaKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University Hangzhou ChinaKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University Hangzhou ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Hangzhou ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Hangzhou ChinaKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University Hangzhou ChinaKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University Hangzhou ChinaWestlake Omics (Hangzhou) Biotechnology Co., Ltd. ChinaKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University Hangzhou ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Hangzhou ChinaDepartment of Clinical Epidemiology, Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang ChinaKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University Hangzhou ChinaSchool of Medicine Zhejiang University Hangzhou ChinaHigh‐grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with 5‐year survival rates below 40%. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients with advanced‐stage HGSOC unsuitable for primary debulking surgery (PDS). However, about 40% of patients receiving this treatment exhibited chemoresistance of uncertain molecular mechanisms and predictability. Here, we built a high‐quality ovary‐specific spectral library containing 130 735 peptides and 10 696 proteins on Orbitrap instruments. Compared to a published DIA pan‐human spectral library (DPHL), this spectral library provides 10% more ovary‐specific and 3% more ovary‐enriched proteins. This library was then applied to analyze data‐independent acquisition (DIA) data of tissue samples from an HGSOC cohort treated with NACT, leading to 10 070 quantified proteins, which is 9.73% more than that with DPHL. We further established a six‐protein classifier by parallel reaction monitoring (PRM) to effectively predict the resistance to additional chemotherapy after IDS (Log‐rank test, P = 0.002). The classifier was validated with 57 patients from an independent clinical center (P = 0.014). Thus, we have developed an ovary‐specific spectral library for targeted proteome analysis, and propose a six‐protein classifier that could potentially predict chemoresistance in HGSOC patients after NACT‐IDS treatment.https://doi.org/10.1002/1878-0261.13410chemotherapy resistancedata‐independent acquisitionmachine learningMS spectral libraryovarian cancertargeted proteomics
spellingShingle Liujia Qian
Jianqing Zhu
Zhangzhi Xue
Tingting Gong
Nan Xiang
Liang Yue
Xue Cai
Wangang Gong
Junjian Wang
Rui Sun
Wenhao Jiang
Weigang Ge
He Wang
Zhiguo Zheng
Qijun Wu
Yi Zhu
Tiannan Guo
Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library
Molecular Oncology
chemotherapy resistance
data‐independent acquisition
machine learning
MS spectral library
ovarian cancer
targeted proteomics
title Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library
title_full Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library
title_fullStr Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library
title_full_unstemmed Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library
title_short Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library
title_sort resistance prediction in high grade serous ovarian carcinoma with neoadjuvant chemotherapy using data independent acquisition proteomics and an ovary specific spectral library
topic chemotherapy resistance
data‐independent acquisition
machine learning
MS spectral library
ovarian cancer
targeted proteomics
url https://doi.org/10.1002/1878-0261.13410
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