AbstractThis study aimed to confirm urinary protein fragments in relation to the presence of pancreatic ductal adenocarcinoma (PDAC) via a C-terminal proteomics strategy using exploratory and validation cohorts. Urinary fragments were examined by iTRAQ-labelling of tryptic peptides and concentrations of C-terminal fragments were evaluated.

摘要本研究旨在通过使用探索性和验证队列的C端蛋白质组学策略来确认与胰腺导管腺癌（PDAC）存在相关的尿蛋白片段。通过胰蛋白酶肽的iTRAQ标记检查尿片段，并评估C端片段的浓度。

Only the urinary CD276 fragment showed a fold change (FC) of > 1.5 with a significant difference of P < 0.01 between healthy (H) and PDAC participants in both the exploratory (H, n = 42; PDAC, n = 39) and validation cohorts (H, n = 36; resectable PDAC, n = 28). The sensitivity and specificity of the CD276 fragment for diagnosing resectable PDAC were 75% and 89%, respectively, in the validation cohort.

只有尿CD276片段显示倍数变化（FC）为1.5，健康（H）和PDAC参与者在探索性（H，n=42；PDAC，n＝39）和验证队列（H，n＝36）；可切除的PDAC，n=28）。在验证队列中，CD276片段诊断可切除PDAC的敏感性和特异性分别为75%和89%。

Postoperative urinary levels of the CD276 fragment were low as compared to those before surgery (n = 18, P < 0.01). Comprehensive C-terminus proteomics identified an increase in the urinary CD276 fragment level as a feature of patients with PDAC. The urinary CD276 fragment is a potential biomarker for detecting resectable PDAC..

与手术前相比，术后尿中CD276片段的水平较低（n=18，P<0.01）。全面的C末端蛋白质组学鉴定出尿CD276片段水平升高是PDAC患者的特征。尿CD276片段是检测可切除PDAC的潜在生物标志物。。

IntroductionWorldwide, pancreatic cancer is a leading cause of cancer-related death. In Japan, pancreatic cancer mortality and morbidity were reported as 37,677 patients in 2020 and 43,865 patients in 2019, respectively, and were associated with a poor prognosis, with a low 5-year survival rate of only 8.5% 1.

引言在世界范围内，胰腺癌是癌症相关死亡的主要原因。在日本，2020年胰腺癌死亡率和发病率分别为37677例和2019年的43865例，与预后不良有关，5年生存率仅为8.5%1。

The small minority of pancreatic cancer patients initially presenting with resectable disease (15–20%) 2,3 is one of the reasons for the poor survival rate, since surgical resection is the only curative treatment for pancreatic cancer. Serum carbohydrate antigen 19-9 (CA19-9) is a validated tumor marker in the management of pancreatic cancer, including for the detection of resectable disease.

。血清碳水化合物抗原19-9（CA19-9）是胰腺癌治疗中经过验证的肿瘤标志物，包括用于检测可切除疾病。

However, the sensitivity of CA19-9 for diagnosing resectable pancreatic cancer is unsatisfactory, at approximately 50–72% 4,5, indicating the urgent need for the development of specific and noninvasive biomarkers.Disease-associated protein alterations, including protein synthesis, maturation and degradation, are reflected at the proteome level and might be detectable in relevant body fluids.

然而，CA19-9诊断可切除胰腺癌的敏感性并不令人满意，约为50-72%4,5，这表明迫切需要开发特异性和非侵入性生物标志物。疾病相关的蛋白质改变，包括蛋白质合成，成熟和降解，反映在蛋白质组水平上，可能在相关体液中检测到。

Urine is an easily accessible bodily fluid that is used for clinical testing. A previous proteomics analysis reported that S100A9 protein was detected in 44% of urine samples, but not in plasma, of pancreatic cancer patients 6, which indicates that urine proteomics might provide tumor-specific biomarkers for pancreatic cancer.

尿液是一种易于获得的体液，用于临床测试。先前的蛋白质组学分析报道，在胰腺癌患者6的44%尿液样本中检测到S100A9蛋白，但在血浆中未检测到，这表明尿液蛋白质组学可能为胰腺癌提供肿瘤特异性生物标志物。

Urine contains C-terminally truncated proteins generated by proteolytic cleavage, such as by shedding of membrane proteins and degradation of protein C-termini. These protein fragments might reflect physiological proteolytic events, as well as disorders induced under disease conditions. Proteomic approaches intended for quantitation of protein C-termini are, thu.

尿液含有由蛋白水解切割产生的C末端截短的蛋白质，例如通过膜蛋白的脱落和蛋白质C末端的降解产生的蛋白质。这些蛋白质片段可能反映了生理蛋白水解事件，以及在疾病条件下引起的疾病。用于定量蛋白质C末端的蛋白质组学方法是，thu。

Data availability

数据可用性

The authors declare that the data supporting the findings of this study are available in the Supplementary Information. Source Data are also provided with this paper. MS proteomics data have been deposited with the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the jPOST partner repository with the dataset identifier PXD041122 and JPST002103..

。本文还提供了源数据。MS蛋白质组学数据已保存在ProteomeXchange Consortium(http://proteomecentral.proteomexchange.org)通过具有数据集标识符PXD041122和JPST002103的jPOST合作伙伴存储库。。

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Download referencesAcknowledgementsThe authors wish to thank Kayo Takei (National Cancer Center Hospital East) and Yuriko Sato (National Cancer Center Hospital East) for their secretarial support.FundingWork on this clinical trial was supported by Funding for the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct) (Grant Number: 16cm0106410h0001), the Practical Research for Innovative Cancer Control (Grant Number: 17ck0106273h0001), and the Project for Cancer Research and Therapeutic Evolution (P-Create) (Grant Number: 17cm0106410h0002), from the Japan Agency for Medical Research and Development (AMED).Author informationAuthor notesThese authors contributed equally: Shuichi Mitsunaga and Nobuaki Okumura.Authors and AffiliationsDivision of Biomarker Discovery, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, JapanShuichi MitsunagaDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, JapanShuichi Mitsunaga & Masafumi IkedaInstitute for Protein Research, Osaka University, Suita, Osaka, JapanNobuaki Okumura, Toshiki Takei & Toshifumi TakaoDivision of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, JapanHironobu TsubouchiDepartment of Surgery and Oncology, Kyushu University, Fukuoka, JapanKohei Nakata & Masafumi NakamuraSecond Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, JapanYuji Kitahata & Hideki MotobayashiDepartment of Bioregulatory Science, Faculty of Medicine, University of Miyazaki, Kiyotake, JapanMasamitsu NakazatoAuthorsShuichi MitsunagaView author publicationsYou can also search for this author in.

下载参考文献致谢作者要感谢Kayo Takei（国家癌症中心医院东）和Yuriko Sato（国家癌症中心医院东）的秘书支持。这项临床试验的资助工作得到了日本医学研究与发展机构（AMED）资助的癌症治疗创新研究开发项目（P-Direct）（资助号：16cm0106410h0001），创新癌症控制实践研究（资助号：17ck0106273h0001）和癌症研究与治疗进化项目（P-Create）（资助号：17cm0106410h0002）的资助。作者信息作者注意到，这些作者做出了同样的贡献：水池光谷和大村信木。作者和附属机构生物标志物发现，探索性肿瘤学研究和临床试验中心，国家癌症中心，Kashiwa，JapanShuichi Mitsunaga国家癌症中心医院肝胆和胰腺肿瘤学系，Kashiwa，JapanShuichi Mitsunaga＆Masafumi IkedaInstitute for Protein Research，Osaka，JapanNobuaki Okumura，Toshiki Takei＆Toshifumi TakaoDivision of Respirology，Rheumatology，Infectious Diseases，and Neurology，Department of Medicine，Faculty of Miyazaki，Kiyotake，JapanHironobu Tsubou九州大学外科与肿瘤学系，福冈，日本中田正平和中村正美和歌山医科大学医学院第二外科，和歌山，日本北田英二和本林秀吉宫崎大学医学院生物调节科学系，JapanMasamitsu NakazatoAuthorsShuichi MitsunagaView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsS.M., N.O.: Conceptualization, data curation, formal analysis, investigation, methodology, writing of the original draft, project management. T.Takao, T.Takei, H.T.: Investigation, resources, supervision. H.S.: Conceptualization, methodology, K.N., M.N., Y.K., H.M., M.I.: Investigation, methodology, M.N.: Funding, project management.

PubMed谷歌学术贡献。M、 ，N.O.：概念化，数据管理，形式分析，调查，方法论，原稿撰写，项目管理。T、 Takao，T.Takei，H.T.：调查，资源，监督。H、 S.：概念化，方法论，K.N.，M.N.，Y.K.，H.M.，M.I.：调查，方法论，M.N.：资金，项目管理。

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Reprints and permissionsAbout this articleCite this articleMitsunaga, S., Okumura, N., Takei, T. et al. Identification of a urinary CD276 fragment for detecting resectable pancreatic cancer using a C-terminal proteomics strategy.

转载和许可本文引用本文Mitsunaga，S.，Okumura，N.，Takei，T。等人使用C端蛋白质组学策略鉴定用于检测可切除胰腺癌的尿CD276片段。

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科学报告1414207（2024）。https://doi.org/10.1038/s41598-024-65093-2Download引文接收日期：2024年3月9日接受日期：2024年6月17日发布日期：2024年6月20日OI：https://doi.org/10.1038/s41598-024-65093-2Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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