{"title":"Altered centriolar cohesion by CEP250 and appendages impact outcome of patients with pancreatic cancer","authors":"","doi":"10.1016/j.pan.2024.06.010","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Pancreatic ductal adenocarcinoma<span><span> (PDAC) is one of the leading cause of cancer death worldwide. PDACs are characterized by </span>centrosome aberrations, but whether centrosome-related genes influence patient outcomes has not been tested.</span></p></div><div><h3>Methods</h3><p><span>Publicly available RNA-sequencing data of patients diagnosed with PDAC were interrogated with unsupervised approaches to identify centrosome protein-encoding genes with prognostic relevance. Candidate genes were validated by </span>immunohistochemistry<span> and multiplex immunofluorescence in a set of clinical PDAC and normal pancreatic tissues.</span></p></div><div><h3>Results</h3><p>Results showed that two genes <em>CEP250</em> and <em>CEP170,</em> involved in centrosome linker and centriolar subdistal appendages, were expressed at high levels in PDAC tissues and were correlated with prognosis of PDAC patients in independent databases.</p><p>Large clustered γ-tubulin-labelled centrosomes were linked together by aberrant circular and planar-shaped CEP250 arrangements in CEP250-high expressing PDACs. Furthermore, PDACs displayed prominent centrosome separation and reduced CEP164-centrosomal labelling associated with acetylated-tubulin staining compared to normal pancreatic tissues. Interestingly, in a small validation cohort, CEP250-high expressing patients had shorter disease free- and overall-survival and almost none of those who received gemcitabine plus nab-paclitaxel first-line therapy achieved a clinical response. In contrast, weak CEP250 expression was associated with long-term survivors or responses to medical treatments.</p></div><div><h3>Conclusions</h3><p>Alteration of the centriolar cohesion and appendages has effect on the survival of patients with PDAC.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pancreatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1424390324006653","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading cause of cancer death worldwide. PDACs are characterized by centrosome aberrations, but whether centrosome-related genes influence patient outcomes has not been tested.
Methods
Publicly available RNA-sequencing data of patients diagnosed with PDAC were interrogated with unsupervised approaches to identify centrosome protein-encoding genes with prognostic relevance. Candidate genes were validated by immunohistochemistry and multiplex immunofluorescence in a set of clinical PDAC and normal pancreatic tissues.
Results
Results showed that two genes CEP250 and CEP170, involved in centrosome linker and centriolar subdistal appendages, were expressed at high levels in PDAC tissues and were correlated with prognosis of PDAC patients in independent databases.
Large clustered γ-tubulin-labelled centrosomes were linked together by aberrant circular and planar-shaped CEP250 arrangements in CEP250-high expressing PDACs. Furthermore, PDACs displayed prominent centrosome separation and reduced CEP164-centrosomal labelling associated with acetylated-tubulin staining compared to normal pancreatic tissues. Interestingly, in a small validation cohort, CEP250-high expressing patients had shorter disease free- and overall-survival and almost none of those who received gemcitabine plus nab-paclitaxel first-line therapy achieved a clinical response. In contrast, weak CEP250 expression was associated with long-term survivors or responses to medical treatments.
Conclusions
Alteration of the centriolar cohesion and appendages has effect on the survival of patients with PDAC.
期刊介绍:
Pancreatology is the official journal of the International Association of Pancreatology (IAP), the European Pancreatic Club (EPC) and several national societies and study groups around the world. Dedicated to the understanding and treatment of exocrine as well as endocrine pancreatic disease, this multidisciplinary periodical publishes original basic, translational and clinical pancreatic research from a range of fields including gastroenterology, oncology, surgery, pharmacology, cellular and molecular biology as well as endocrinology, immunology and epidemiology. Readers can expect to gain new insights into pancreatic physiology and into the pathogenesis, diagnosis, therapeutic approaches and prognosis of pancreatic diseases. The journal features original articles, case reports, consensus guidelines and topical, cutting edge reviews, thus representing a source of valuable, novel information for clinical and basic researchers alike.