高级别浆液性卵巢癌（HGSOC）是卵巢癌中最常见的亚型，5年生存率低于40％。 对于无法接受原发性减灭手术（PDS）的晚期HGSOC患者，建议采用新辅助化疗（NACT）后进行间隔性减灭手术（IDS）。 然而，接受此治疗的患者中约有40％的人表现出未知分子机制和可预测性的趋化耐药性。 在这里，我们建立了一个包含130,735个肽和10,696个蛋白质的高质量卵巢组织特异性光谱库，该库使用Orbitrap仪器进行分析。 与已发表的DIA泛人类光谱库（DPHL）相比，该光谱库提供了10％以上的卵巢特异性和3％以上的卵巢富集蛋白质。 然后，将该库应用于采用NACT治疗的HGSOC队列的组织样本的数据无关采集（DIA）数据分析，导致10,070个定量蛋白质，比使用DPHL多9.73％。 我们进一步通过并行反应监测（PRM）建立了一种六蛋白分类器，以有效预测IDS后进一步化疗的抗药性（对数秩和检验，p = 0.002）。该分类器通过来自独立临床中心的57名患者进行验证（p = 0.014）。因此，我们开发了一种针对蛋白组学分析的卵巢特异性光谱库，并提出了一种六蛋白分类器，该分类器可能能够预测HGSOC患者在NACT-IDS治疗后的趋化耐药性。本文受版权保护，保留所有权利。

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 ovarian-tissue-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 predicts chemoresistance in HGSOC patients after NACT-IDS treatment.This article is protected by copyright. All rights reserved.