Nina Schraps, Jacob Constantin Port, Anne Menz, Florian Viehweger, Seyma Büyücek, David Dum, Ria Schlichter, Andrea Hinsch, Christoph Fraune, Christian Bernreuther, Martina Kluth, Claudia Hube-Magg, Katharina Möller, Viktor Reiswich, Andreas M. Luebke, Patrick Lebok, Sören Weidemann, Guido Sauter, Maximilian Lennartz, Frank Jacobsen, Till S. Clauditz, Andreas H. Marx, Ronald Simon, Stefan Steurer, Baris Mercanoglu, Nathaniel Melling, Thilo Hackert, Eike Burandt, Natalia Gorbokon, Sarah Minner, Till Krech, Florian Lutz
{"title":"人类癌症中 AGR2 表达的普遍性和重要性。","authors":"Nina Schraps, Jacob Constantin Port, Anne Menz, Florian Viehweger, Seyma Büyücek, David Dum, Ria Schlichter, Andrea Hinsch, Christoph Fraune, Christian Bernreuther, Martina Kluth, Claudia Hube-Magg, Katharina Möller, Viktor Reiswich, Andreas M. Luebke, Patrick Lebok, Sören Weidemann, Guido Sauter, Maximilian Lennartz, Frank Jacobsen, Till S. Clauditz, Andreas H. Marx, Ronald Simon, Stefan Steurer, Baris Mercanoglu, Nathaniel Melling, Thilo Hackert, Eike Burandt, Natalia Gorbokon, Sarah Minner, Till Krech, Florian Lutz","doi":"10.1002/cam4.70407","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Backround</h3>\n \n <p>Anterior gradient 2 (AGR2) is a resident endoplasmic reticulum (ER) protein with a vital role in embryonal development, mucus maturation, tissue regeneration, and wound healing.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>To determine the prevalence and clinical significance of AGR2 expression in cancer, a tissue microarray containing 14,966 tumors from 134 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>AGR2 positivity was found in 103 of 134 tumor categories, and 83 tumor categories contained at least one strongly positive case. AGR2 expression was most frequently seen in tumors of the female genital tract, particularly adenocarcinomas (up to 100%), various breast cancer subtypes (57.1%–100%), urothelial carcinoma (74.6%–100%), adenocarcinomas of the upper and lower gastrointestinal tract (93.6%–99.6%), and pancreaticobiliary cancers (65.2%–98.2%). AGR2 positivity was slightly less common in squamous cell carcinomas (46.4%–77.3%) and mainly absent in mesenchymal and lymphoid tumors. While AGR2 expression was only weak or absent in the normal thyroid, it was moderate to strong in 46.0% of adenomas, 52.8% of follicular carcinomas, and 81.8% of papillary carcinomas of the thyroid. High AGR2 expression was strongly linked to poor ISUP (<i>p</i> < 0.0001), Fuhrman (<i>p</i> < 0.0001), and Thoenes (<i>p</i> < 0.0001) grades as well as advanced pT stage (<i>p</i> = 0.0035) in clear cell renal cell carcinoma (ccRCC). Low AGR2 expression was associated with high BRE grade in breast cancer (<i>p</i> = 0.0049), nodal metastasis (<i>p</i> = 0.0275) and RAS mutation (<i>p</i> = 0.0136) in colorectal cancer, nodal metastasis (<i>p</i> = 0.0482) in endometrioid endometrial carcinoma, high grade in noninvasive urothelial carcinoma (<i>p</i> = 0.0003), and invasive tumor growth in urothelial carcinoma (<i>p</i> < 0.0001).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>It is concluded that AGR2 expression occurs in a broad range of different tumor entities and that AGR2 assessment may serve as a diagnostic aid for the distinction of thyroidal neoplasms and as a prognostic marker in various cancer types.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557986/pdf/","citationCount":"0","resultStr":"{\"title\":\"Prevalence and Significance of AGR2 Expression in Human Cancer\",\"authors\":\"Nina Schraps, Jacob Constantin Port, Anne Menz, Florian Viehweger, Seyma Büyücek, David Dum, Ria Schlichter, Andrea Hinsch, Christoph Fraune, Christian Bernreuther, Martina Kluth, Claudia Hube-Magg, Katharina Möller, Viktor Reiswich, Andreas M. Luebke, Patrick Lebok, Sören Weidemann, Guido Sauter, Maximilian Lennartz, Frank Jacobsen, Till S. Clauditz, Andreas H. Marx, Ronald Simon, Stefan Steurer, Baris Mercanoglu, Nathaniel Melling, Thilo Hackert, Eike Burandt, Natalia Gorbokon, Sarah Minner, Till Krech, Florian Lutz\",\"doi\":\"10.1002/cam4.70407\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Backround</h3>\\n \\n <p>Anterior gradient 2 (AGR2) is a resident endoplasmic reticulum (ER) protein with a vital role in embryonal development, mucus maturation, tissue regeneration, and wound healing.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>To determine the prevalence and clinical significance of AGR2 expression in cancer, a tissue microarray containing 14,966 tumors from 134 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>AGR2 positivity was found in 103 of 134 tumor categories, and 83 tumor categories contained at least one strongly positive case. AGR2 expression was most frequently seen in tumors of the female genital tract, particularly adenocarcinomas (up to 100%), various breast cancer subtypes (57.1%–100%), urothelial carcinoma (74.6%–100%), adenocarcinomas of the upper and lower gastrointestinal tract (93.6%–99.6%), and pancreaticobiliary cancers (65.2%–98.2%). AGR2 positivity was slightly less common in squamous cell carcinomas (46.4%–77.3%) and mainly absent in mesenchymal and lymphoid tumors. While AGR2 expression was only weak or absent in the normal thyroid, it was moderate to strong in 46.0% of adenomas, 52.8% of follicular carcinomas, and 81.8% of papillary carcinomas of the thyroid. High AGR2 expression was strongly linked to poor ISUP (<i>p</i> < 0.0001), Fuhrman (<i>p</i> < 0.0001), and Thoenes (<i>p</i> < 0.0001) grades as well as advanced pT stage (<i>p</i> = 0.0035) in clear cell renal cell carcinoma (ccRCC). Low AGR2 expression was associated with high BRE grade in breast cancer (<i>p</i> = 0.0049), nodal metastasis (<i>p</i> = 0.0275) and RAS mutation (<i>p</i> = 0.0136) in colorectal cancer, nodal metastasis (<i>p</i> = 0.0482) in endometrioid endometrial carcinoma, high grade in noninvasive urothelial carcinoma (<i>p</i> = 0.0003), and invasive tumor growth in urothelial carcinoma (<i>p</i> < 0.0001).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>It is concluded that AGR2 expression occurs in a broad range of different tumor entities and that AGR2 assessment may serve as a diagnostic aid for the distinction of thyroidal neoplasms and as a prognostic marker in various cancer types.</p>\\n </section>\\n </div>\",\"PeriodicalId\":139,\"journal\":{\"name\":\"Cancer Medicine\",\"volume\":\"13 21\",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-11-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557986/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70407\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70407","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Prevalence and Significance of AGR2 Expression in Human Cancer
Backround
Anterior gradient 2 (AGR2) is a resident endoplasmic reticulum (ER) protein with a vital role in embryonal development, mucus maturation, tissue regeneration, and wound healing.
Methods
To determine the prevalence and clinical significance of AGR2 expression in cancer, a tissue microarray containing 14,966 tumors from 134 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC).
Results
AGR2 positivity was found in 103 of 134 tumor categories, and 83 tumor categories contained at least one strongly positive case. AGR2 expression was most frequently seen in tumors of the female genital tract, particularly adenocarcinomas (up to 100%), various breast cancer subtypes (57.1%–100%), urothelial carcinoma (74.6%–100%), adenocarcinomas of the upper and lower gastrointestinal tract (93.6%–99.6%), and pancreaticobiliary cancers (65.2%–98.2%). AGR2 positivity was slightly less common in squamous cell carcinomas (46.4%–77.3%) and mainly absent in mesenchymal and lymphoid tumors. While AGR2 expression was only weak or absent in the normal thyroid, it was moderate to strong in 46.0% of adenomas, 52.8% of follicular carcinomas, and 81.8% of papillary carcinomas of the thyroid. High AGR2 expression was strongly linked to poor ISUP (p < 0.0001), Fuhrman (p < 0.0001), and Thoenes (p < 0.0001) grades as well as advanced pT stage (p = 0.0035) in clear cell renal cell carcinoma (ccRCC). Low AGR2 expression was associated with high BRE grade in breast cancer (p = 0.0049), nodal metastasis (p = 0.0275) and RAS mutation (p = 0.0136) in colorectal cancer, nodal metastasis (p = 0.0482) in endometrioid endometrial carcinoma, high grade in noninvasive urothelial carcinoma (p = 0.0003), and invasive tumor growth in urothelial carcinoma (p < 0.0001).
Conclusions
It is concluded that AGR2 expression occurs in a broad range of different tumor entities and that AGR2 assessment may serve as a diagnostic aid for the distinction of thyroidal neoplasms and as a prognostic marker in various cancer types.
期刊介绍：
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
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