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An ERS-related risk signature was built via Lasso regression and evaluated across prognosis, immune effects, metabolic impact, mutational features, and therapy correlations using bioinformatic analyses. Functional work assessed KDELR3 and YWHAZ in pancreatic cancer cells and xenografts. ERS risk score serves as an independent prognostic factor linked to metabolic reprogramming and anti-tumour immune response, and may predict immune checkpoint blockade efficacy.",{"@graph":69,"@context":123},[70,84,106],{"@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/endoplasmic-reticulum-stress-regulators-exhibit-different-prognostic-therapeutic-and-immune-landscapes-in-pancreatic-adenocarcinoma/333222/",{"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/endoplasmic-reticulum-stress-regulators-exhibit-different-prognostic-therapeutic-and-immune-landscapes-in-pancreatic-adenocarcinoma/333222.png","ImageObject",300,407,{"name":92,"@type":93},"Anda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What was the main objective of the study in pancreatic adenocarcinoma?","Question",{"text":113,"@type":114},"To clarify how ERS regulatory genes shape prognostic, therapeutic, and immune landscapes in PAAD and to identify ERS-related biomarkers or targets.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was the ERS-related risk signature constructed and evaluated?",{"text":118,"@type":114},"An ERS-related risk signature was constructed using Lasso regression, then assessed for prognostic value, immune effects, metabolic influence, mutational features, and therapeutic correlations using multiple bioinformatic approaches.",{"name":120,"@type":111,"acceptedAnswer":121},"What roles do KDELR3 and YWHAZ play according to functional experiments?",{"text":122,"@type":114},"Overexpression of KDELR3 and YWHAZ promoted proliferation, migration, and invasion in pancreatic cancer cell models, while silencing KDELR3 suppressed tumour growth in a xenograft model.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},333222,1790193959,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","DOI: 10. 1111/jcmm.18092  \nOR I G I NAL ART I C L E  \nEndoplasmic reticulum stress regulators exhibit different prognostic, therapeutic and immune landscapes in pancreatic adenocarcinoma  \nShanshan Liu1 | Kaini He2 | Longbao Yang2 | Fangshi Xu3 | Xiaoguang Cui1 | Li Qu1 | Xueyi Li1 | Bin-cheng Ren1   \n1Department of Rheumatology and Immunology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China 2Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China  \n3 Department of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China  \nCorrespondence  \nBin-cheng Ren, Department of Rheumatology and Immunology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, West Five Road, Xi'an, Shaanxi 710004, China.  \nEmail: [renbincheng7@163.com](renbincheng7@163.com)  \nAbstract  \nEndoplasmic reticulum stress (ERS) and unfolded protein response are the critical processes of tumour biology. However, the roles of ERS regulatory genes in pancreatic adenocarcinoma (PAAD) remain elusive. A novel ERS-related risk signature was constructed using the Lasso regression analysis. Its prognostic value, immune effect, metabolic influence, mutational feature and therapeutic correlation were comprehensively analysed through multiple bioinformatic approaches. The biofunctions of KDELR3 and YWHAZ in pancreatic cancer (PC) cells were also investigated through colony formation, Transwell assays, flow cytometric detection and a xenograft model. The upstream miRNA regulatory mechanism of KDELR3 was predicted and validated. ERS risk score was identified as an independent prognostic factor and could improve traditional prognostic model. Meanwhile, it was closely associated with metabolic reprogramming and tumour immune. High ERS risk enhanced glycolysis process and nucleotide metabolism, but was unfavourable for anti-tumour immune response. Moreover, ERS risk score could act as a potential biomarker for predicting the efficacy of ICBs. Overexpression of KDELR3 and YWHAZ stimulated the proliferation, migration and invasion of SW1990 and BxPC-3 cells. Silencing KDELR3 suppressed tumour growth in a xenograft model. miR-137 could weaken the malignant potentials of PC cells through inhibiting KDELR3 (5′-AGCAAUAA-3 ′) . ERS risk score greatly contributed to PAAD clinical assessment. KDELR3 and YWHAZ possessed cancer-promoting capacities, showing promise as a novel treatment target.  \nK E Y WO R D S  \nendoplasmic reticulum stress, immune checkpoint blockade, immune microenvironment, pancreatic adenocarcinoma, prognosis, unfolded protein response  \nShanshan Liu, Kaini He, and Longbao Yang contributed equally to this work.  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.  \n1 | INTRODUCTION  \nPancreatic adenocarcinoma (PAAD), a common abdominal cancer, is associated with high malignancy and mortality. According to the American Cancer Society, PAAD accounts for >400,000 deaths in the United States each year, contributing to 4.7% of all cancerrelated deaths.1 The 5-year overall survival rate (OSR) of patients with PAAD is \u003C35% .2 Approximately 10% of patients with PAADare diagnosed with localized carcinoma and are eligible for surgical excision.3 The incidence of pancreatic cancer (PC) has been increasing.3 Recent advances in PAAD treatment have not improved the therapeutic outcomes. FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) and gemcitabine, which are the mainstream chemotherapy regimens for PAAD, have not increased the median disease-free survival to >25 months.4 Additionally, programmed cell death protein 1/ligand 1 (P","cbCaikZQdFHJU344","https://ap.wps.com/l/cbCaikZQdFHJU344","pdf",55536990,26,"English","# Introduction\n## Endoplasmic reticulum stress and unfolded protein response in tumour biology\n## Need for improved prognosis and therapeutic strategies in PAAD\n## KDELR3 and its roles in ERS/UPR","[{\"question\":\"What was the main objective of the study in pancreatic adenocarcinoma?\",\"answer\":\"To clarify how ERS regulatory genes shape prognostic, therapeutic, and immune landscapes in PAAD and to identify ERS-related biomarkers or targets.\"},{\"question\":\"How was the ERS-related risk signature constructed and evaluated?\",\"answer\":\"An ERS-related risk signature was constructed using Lasso regression, then assessed for prognostic value, immune effects, metabolic influence, mutational features, and therapeutic correlations using multiple bioinformatic approaches.\"},{\"question\":\"What roles do KDELR3 and YWHAZ play according to functional experiments?\",\"answer\":\"Overexpression of KDELR3 and YWHAZ promoted proliferation, migration, and invasion in pancreatic cancer cell models, while silencing KDELR3 suppressed tumour growth in a xenograft model.\"}]","Endoplasmic reticulum stress regulators exhibit different prognostic, therapeutic and immune landscapes in pancreatic adenocarcinoma | PDF",1790001527,66]