[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-345525-105":59,"doc-detail-345525-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","kallikrein-related-peptidases-7-and-10-and-their-substrate-desmoglein-3-are-upregulated-in-early-stage-pancreatic-cancerous-lesions","Kallikrein related peptidases 7 and 10 and their substrate desmoglein 3 are upregulated in early stage pancreatic cancerous lesions","","Differential expression of Kallikreins (KLKs) has been characterized in metastatic pancreatic ductal adenocarcinoma (PDAC), but their value for early detection remained unclear. Comprehensive in silico and in situ analyses show that KLK7 and KLK10 RNA and protein are upregulated early, marking carcinoma in-situ lesions (stage 0, PanIN3) and stage 1 PDAC. Non-cancerous low-grade lesions stain negative. KLK7 and KLK10 are co-expressed with desmoglein-3 (DSG3), generating a 30 kDa extracellular fragment. Expression analysis of KLK7, KLK10, and cleaved DSG3 may distinguish earliest cancerous from non-cancerous lesions in the pancreas.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/kallikrein-related-peptidases-7-and-10-and-their-substrate-desmoglein-3-are-upregulated-in-early-stage-pancreatic-cancerous-lesions/345525/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/kallikrein-related-peptidases-7-and-10-and-their-substrate-desmoglein-3-are-upregulated-in-early-stage-pancreatic-cancerous-lesions/345525.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What did the study find about KLK7 and KLK10 during early PDAC development?","Question",{"text":112,"@type":113},"KLK7 and KLK10 RNA and protein are upregulated early, marking carcinoma in-situ lesions (stage 0, PanIN3) and stage 1 PDAC, while non-cancerous low-grade lesions stain negative.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How are KLK7 and KLK10 related to desmoglein-3 (DSG3) in PDAC?",{"text":117,"@type":113},"Both KLKs are co-expressed with DSG3 in PDAC cell lines and in samples from treatment-naïve patients. DSG3 is cleaved by KLK7 and KLK10 to produce a 30 kDa extracellular fragment.",{"name":119,"@type":110,"acceptedAnswer":120},"Why might KLK7, KLK10, and cleaved DSG3 be useful as diagnostic biomarkers?",{"text":121,"@type":113},"The data suggest these markers could help distinguish non-cancerous low-grade lesions from the earliest cancerous lesions in the pancreas by reflecting early-stage upregulation and substrate cleavage.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},345525,1790188917,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nKallikrein related peptidases 7 and  \n10 and their substrate desmoglein  \n3 are upregulated in early stage pancreatic cancerous lesions  \nJillian Eisenhauer1,5, Ryan Argo1,5, Alicia K. Fleming Martinez1,5, Emir Maldosevic1, Ligia I. Bastea1, Cody J. Wehrkamp1, Heike R. Döppler1, Brandy H. Edenfield1, Jason T. Lewis2, Michael B. Wallace3 & Peter Storz1,3,4􀀍  \nDifferential expression of Kallikreins (KLKs) was described for established metastatic pancreatic ductaladenocarcinoma (PDAC), but their potential as markers for early detection is not known. We have performed comprehensive in silico and in situ analyses of KLK expression in PDAC at different stages of tumor development. We found that upregulation of KLK7 and KLK10 RNA and protein occurs early in tumor development and marks carcinoma in-situ lesions (stage 0, PanIN3) and early-stage (stage 1) PDAC, while non-cancerous low grade lesions stain negative for these proteases. Moreover, both KLKs are co-expressed with desmoglein-3 (DSG3) in PDAC cell lines as well as PDAC samples from treatment naïve patients. DSG3 serves as a substrate for both KLK7 and KLK10 resulting in a 30 kDa extracellular fragment. Overall, our data suggest that analyses for expression of KLK7 and KLK10 as well as their substrates could have potential as diagnostic biomarkers to distinguish non-cancerous low-grade lesions from earliest cancerous lesions in the pancreas.  \nKeywords Pancreatic cancer, PDAC, PanIN lesions, KLK7, KLK10, Desmoglein 3  \nPancreatic cancer is a devastating disease ranking as the third leading cause of cancer death in the US1. The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which has a 5-year survival rate of 13%1. Many PDAC patients are diagnosed after metastasis has occurred, greatly limiting the effectiveness of available treatments. Therefore, to improve patient outcomes, there is a need for detecting pancreatic cancer early in its progression.  \nDifferential expression or activity of proteases can be utilized for PDAC detection. For example, a promising new test (PAC-MANN) is based on a single MMP-sensitive probe that distinguishes PDAC from controls with 79% ± 6% accuracy2. Kallikreins (KLKs) are serine proteases that serve regulatory functions throughout the body, including skin desquamation, wound healing, and inflammation, through their ability to break down adherens junction proteins and activate inflammatory cytokines3–7. However, overactivation of KLKs has been linked to conditions like Netherton syndrome and psoriasis, as well as a variety of cancers3–5,7–9.  \nKLKs contribute to multiple aspects of tumor development and progression including cell proliferation and survival and pro-angiogenic effects8. Through the excessive breakdown of cell adhesion proteins and extracellular matrix (ECM) components, KLKs mediate cancer cell detachment from the tumor and invasion3–6. Additionally, KLK activity has been shown to promote epidermal growth factor receptor (EGFR) pathway signaling, which can induce epithelial to mesenchymal transition (EMT) in cancer cells4,9–11 but also was linked to earliest events driving the initiation of pancreatic cancer12.  \nKLK substrates include the ECM proteins fibronectin and laminin13, 14, but also desmogleins, which are involved in maintaining desmosomes to anchor neighboring cells. For example, desmoglein 1 (DSG1) is a substrate for KLK5 in oral squamous carcinoma3, and desmoglein 2 (DSG2) is a substrate for KLK7 in pancreatic  \n1Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA.  \n2Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL 32224, USA. 3Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL 32224, USA. 4Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. 5These authors contributed equally to this work: ","cbCaitKE320uo5yI","https://ap.wps.com/l/cbCaitKE320uo5yI","pdf",1930042,"English","# Differential expression of KLKs\n## Early upregulation in PDAC stages\n## Co-expression with desmoglein-3\n# Biological rationale for protease-based detection\n## KLK functions in tumor progression\n## Substrates and desmosome disruption\n# Study approach and findings\n## Early detection marker candidates","[{\"question\":\"What did the study find about KLK7 and KLK10 during early PDAC development?\",\"answer\":\"KLK7 and KLK10 RNA and protein are upregulated early, marking carcinoma in-situ lesions (stage 0, PanIN3) and stage 1 PDAC, while non-cancerous low-grade lesions stain negative.\"},{\"question\":\"How are KLK7 and KLK10 related to desmoglein-3 (DSG3) in PDAC?\",\"answer\":\"Both KLKs are co-expressed with DSG3 in PDAC cell lines and in samples from treatment-naïve patients. DSG3 is cleaved by KLK7 and KLK10 to produce a 30 kDa extracellular fragment.\"},{\"question\":\"Why might KLK7, KLK10, and cleaved DSG3 be useful as diagnostic biomarkers?\",\"answer\":\"The data suggest these markers could help distinguish non-cancerous low-grade lesions from the earliest cancerous lesions in the pancreas by reflecting early-stage upregulation and substrate cleavage.\"}]","Kallikrein related peptidases 7 and 10 and their substrate desmoglein 3 are upregulated in early stage pancreatic cancerous lesions | PDF",1790057972,25]