{"title":"kr<s:1> ppel样因子4突变对胰腺导管内乳头状黏液瘤临床病理特征及相关蛋白表达的影响","authors":"Yoshitaka Nagamine, Miyo Tomita, Munekazu Yamakuchi, Yuto Hozaka, Takashi Okumura, Hideyuki Oi, Kosuke Fukuda, Tetsuya Idichi, Yoichi Yamasaki, Yuko Mataki, Yota Kawasaki, Toshiaki Akahane, Michiyo Higashi, Teruto Hashiguchi, Akihide Tanimoto, Takao Ohtsuka","doi":"10.1016/j.pan.2025.09.028","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/objectives: </strong>Krüppel-like factor 4 (KLF4) hotspot mutations are linked to non-invasive intraductal papillary mucinous neoplasms (IPMNs); however, the molecular mechanisms driving their progression remain unclear. Therefore, in this study, we aimed to identify the signaling pathways associated with KLF4 mutations and their roles in IPMNs.</p><p><strong>Methods: </strong>Thirty-three resected specimens of IPMNs were collected. Associations between genetic alterations in KLF4 and the expression levels of KLF4 protein as well as its related signaling proteins, including p21, p27, and cyclin D, were assessed.</p><p><strong>Results: </strong>KLF4 mutations were found in eight specimens of IPMNs (24 %), all of which were non-invasive lesions and non-intestinal type; of them, seven (87.5 %) showed GNAS mutations. p21 expression was significantly elevated in KLF4-mutated IPMNs (p < 0.01), whereas p27 and cyclin D1 levels were not significantly altered compared with KLF4 wild-type IPMNs. KLF4 and p21 expression levels were significantly elevated in non-invasive lesions compared with invasive lesions (p < 0.05). Higher KLF4 expression was observed in GNAS-mutated IPMNs than in GNAS wild-type IPMNs (p < 0.05).</p><p><strong>Conclusions: </strong>KLF4 mutations might enhance p21 expression, possibly influencing the indolent characteristics of non-invasive IPMNs and providing a new biomarker strategy for risk stratification in patients with IPMNs.</p>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of Krüppel-like factor 4 mutation on the clinicopathological characteristics and its related protein expressions in intraductal papillary mucinous neoplasm of the pancreas.\",\"authors\":\"Yoshitaka Nagamine, Miyo Tomita, Munekazu Yamakuchi, Yuto Hozaka, Takashi Okumura, Hideyuki Oi, Kosuke Fukuda, Tetsuya Idichi, Yoichi Yamasaki, Yuko Mataki, Yota Kawasaki, Toshiaki Akahane, Michiyo Higashi, Teruto Hashiguchi, Akihide Tanimoto, Takao Ohtsuka\",\"doi\":\"10.1016/j.pan.2025.09.028\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/objectives: </strong>Krüppel-like factor 4 (KLF4) hotspot mutations are linked to non-invasive intraductal papillary mucinous neoplasms (IPMNs); however, the molecular mechanisms driving their progression remain unclear. Therefore, in this study, we aimed to identify the signaling pathways associated with KLF4 mutations and their roles in IPMNs.</p><p><strong>Methods: </strong>Thirty-three resected specimens of IPMNs were collected. Associations between genetic alterations in KLF4 and the expression levels of KLF4 protein as well as its related signaling proteins, including p21, p27, and cyclin D, were assessed.</p><p><strong>Results: </strong>KLF4 mutations were found in eight specimens of IPMNs (24 %), all of which were non-invasive lesions and non-intestinal type; of them, seven (87.5 %) showed GNAS mutations. p21 expression was significantly elevated in KLF4-mutated IPMNs (p < 0.01), whereas p27 and cyclin D1 levels were not significantly altered compared with KLF4 wild-type IPMNs. KLF4 and p21 expression levels were significantly elevated in non-invasive lesions compared with invasive lesions (p < 0.05). Higher KLF4 expression was observed in GNAS-mutated IPMNs than in GNAS wild-type IPMNs (p < 0.05).</p><p><strong>Conclusions: </strong>KLF4 mutations might enhance p21 expression, possibly influencing the indolent characteristics of non-invasive IPMNs and providing a new biomarker strategy for risk stratification in patients with IPMNs.</p>\",\"PeriodicalId\":19976,\"journal\":{\"name\":\"Pancreatology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pancreatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.pan.2025.09.028\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pancreatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.pan.2025.09.028","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Effects of Krüppel-like factor 4 mutation on the clinicopathological characteristics and its related protein expressions in intraductal papillary mucinous neoplasm of the pancreas.
Background/objectives: Krüppel-like factor 4 (KLF4) hotspot mutations are linked to non-invasive intraductal papillary mucinous neoplasms (IPMNs); however, the molecular mechanisms driving their progression remain unclear. Therefore, in this study, we aimed to identify the signaling pathways associated with KLF4 mutations and their roles in IPMNs.
Methods: Thirty-three resected specimens of IPMNs were collected. Associations between genetic alterations in KLF4 and the expression levels of KLF4 protein as well as its related signaling proteins, including p21, p27, and cyclin D, were assessed.
Results: KLF4 mutations were found in eight specimens of IPMNs (24 %), all of which were non-invasive lesions and non-intestinal type; of them, seven (87.5 %) showed GNAS mutations. p21 expression was significantly elevated in KLF4-mutated IPMNs (p < 0.01), whereas p27 and cyclin D1 levels were not significantly altered compared with KLF4 wild-type IPMNs. KLF4 and p21 expression levels were significantly elevated in non-invasive lesions compared with invasive lesions (p < 0.05). Higher KLF4 expression was observed in GNAS-mutated IPMNs than in GNAS wild-type IPMNs (p < 0.05).
Conclusions: KLF4 mutations might enhance p21 expression, possibly influencing the indolent characteristics of non-invasive IPMNs and providing a new biomarker strategy for risk stratification in patients with IPMNs.
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.
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