{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T17:30:18Z","timestamp":1757611818532,"version":"3.44.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cholesterol plays a role in tumorigenesis. However, the association between remnant cholesterol and pancreatic neuroendocrine neoplasms (PNENs) has not been clarified. In the present study, we explored the association between the remnant cholesterol level and the World Organization Health Grade of PNENs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The clinical and histopathological characteristics of PNEN patients who underwent surgery at our institution were retrospectively analyzed. Remnant cholesterol was calculated as total cholesterol - high-density lipoprotein cholesterol+low-density lipoprotein cholesterol. The remnant cholesterol\/cholesterol ratio was also calculated. Grade 3 PNENs and pancreatic neuroendocrine carcinoma (PNEC) were defined as high-grade PNENs. The relationship between remnant cholesterol or the remnant cholesterol\/cholesterol ratio and PNENs was analyzed using multivariable logistic regression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with high-grade PNENs had higher remnant cholesterol levels and remnant cholesterol\/cholesterol ratios than did those with low- and moderate-grade PNENs (<jats:italic>P<\/jats:italic> &amp;lt; 0.01). High proportions of patients with a remnant cholesterol concentration &amp;gt; 1.2 and a remnant cholesterol\/cholesterol ratio &amp;gt; 0.26 were observed in patients with high-grade PNENs compared to those with low and moderate PNENs (27.74% vs 9.27%, <jats:italic>P<\/jats:italic> = 0.02; 19.56% vs 7.28%, <jats:italic>P<\/jats:italic> = 0.016). Multivariate logistic regression analysis revealed that remnant cholesterol was associated with high-grade PNENs (odds ratio (OR) =2.41, 95% confidence interval (CI): 1.28 - 4.56). Similar associations were observed between high-grade PNENs and a remnant cholesterol concentration greater than 1.2 (OR = 3.34, 95% CI: 1.15 - 9.68). High-grade PNENs were also associated with the remnant cholesterol\/cholesterol ratio (OR = 1.45, 95% CI: 1.06 - 2.02, for continuous data; OR = 4.00, 95% CI: 1.32 - 12.09, for cholesterol\/cholesterol ratio &amp;gt; 0.26). Similar associations were observed between the remnant cholesterol level and the remnant cholesterol\/cholesterol ratio and PNEC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A high remnant cholesterol level and a high remnant cholesterol\/cholesterol ratio were associated with high-grade PNENs or PNECs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1616523","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T04:12:25Z","timestamp":1756959145000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The relationship between remnant cholesterol and WHO grade of pancreatic neuroendocrine neoplasms"],"prefix":"10.3389","volume":"16","author":[{"given":"Hao","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongkang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuangen","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn351","article-title":"Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival","volume":"19","author":"Halfdanarson","year":"2008","journal-title":"Ann Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0589","article-title":"Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States","volume":"3","author":"Dasari","year":"2017","journal-title":"JAMA Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-042320-011248","article-title":"Progress in the management of\u2002Pancreatic\u2002Neuroendocrine\u2002Tumors","volume":"73","author":"Chang","year":"2022","journal-title":"Annu Rev Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.615082","article-title":"Diabetes in patients with pancreatic neuroendocrine neoplasms","volume":"11","author":"Zhuge","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.17.18417","article-title":"Prediction of\u2002Pancreatic\u2002Neuroendocrine\u2002Tumor\u2002Grade\u2002Based on CT features and texture analysis","volume":"210","author":"Canellas","year":"2018","journal-title":"AJR Am J Roentgenol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1016\/j.soc.2019.11.008","article-title":"Surgical management of pancreatic neuroendocrine tumors","volume":"15","author":"Sulciner","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0174-0","article-title":"Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities","volume":"2","author":"Huang","year":"2020","journal-title":"Nat Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0976-4","article-title":"Blood lipids and lipoproteins in relation to incidence and mortality risks for CVD and cancer in the prospective EPIC-Heidelberg cohort","volume":"15","author":"Katzke","year":"2017","journal-title":"BMC Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-023-06917-z","article-title":"Cholesterol and breast\u2002cancer\u2002risk: a cohort study using health insurance claims and health checkup databases","volume":"199","author":"Narii","year":"2023","journal-title":"Breast Cancer Res Treat"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e1003302","DOI":"10.1371\/journal.pmed.1003302","article-title":"The relationship between circulating lipids and breast\u2002cancer\u2002risk: A Mendelian randomization study","volume":"17","author":"Johnson","year":"2020","journal-title":"PloS Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-017-0030-9","article-title":"Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study","volume":"21","author":"Jamnagerwalla","year":"2018","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"B12","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/s40001-022-00784-y","article-title":"The association between\u2002serum\u2002lipid\u2002levels and histological type of breast\u2002cancer","volume":"27","author":"Wang","year":"2022","journal-title":"Eur J Med Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.01.039","article-title":"Phases of metabolic and soft tissue changes in months preceding a diagnosis of pancreatic ductal adenocarcinoma","volume":"156","author":"Sah","year":"2019","journal-title":"Gastroenterology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"188394","DOI":"10.1016\/j.bbcan.2020.188394","article-title":"Cholesterol\u2002metabolism: New functions and therapeutic approaches in\u2002cancer","volume":"1874","author":"Xu","year":"2020","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"B15","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/s41419-023-05987-7","article-title":"SQLE promotes\u2002pancreatic\u2002cancer\u2002growth by attenuating ER stress and activating lipid rafts-regulated Src\/PI3K\/Akt signaling pathway","volume":"14","author":"Xu","year":"2023","journal-title":"Cell Death Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.168","article-title":"Abrogating\u2002cholesterol\u2002esterification\u2002suppresses\u2002growth\u2002and metastasis of pancreatic cancer","volume":"35","author":"Li","year":"2016","journal-title":"Oncogene"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-024-03767-7","article-title":"Dyslipidemia, lipid-lowering agents and neuroendocrine neoplasms: new horizons","volume":"85","author":"Modica","year":"2024","journal-title":"Endocrine"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.3390\/metabo12111057","article-title":"Lipid metabolism and homeostasis in patients with neuroendocrine neoplasms: from risk factor to potential therapeutic target","volume":"12","author":"Modica","year":"2022","journal-title":"Metabolites"},{"key":"B19","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12944-022-01669-z","article-title":"The associations between serum high-density lipoprotein\u2002cholesterol\u2002levels and Malignant behavior in\u2002pancreatic\u2002neuroendocrine neoplasms","volume":"21","author":"Quan","year":"2022","journal-title":"Lipids Health Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.10.029","article-title":"Remnant\u2002Cholesterol\u2002and atherosclerotic cardiovascular disease risk","volume":"76","author":"Burnett","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab432","article-title":"Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study","volume":"42","author":"Quispe","year":"2021","journal-title":"Eur Heart J"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab705","article-title":"Elevated remnant cholesterol increases the risk of peripheral artery disease, myocardial infarction, and ischemic stroke: a cohort-based study","volume":"43","author":"Wadstr\u00f6m","year":"2022","journal-title":"Eur Heart J"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-024-03910-4","article-title":"The association between non-HDL\u2002cholesterol\u2002and high-grade pancreatic neuroendocrine neoplasms","volume":"86","author":"Zhou","year":"2024","journal-title":"Endocrine"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01079-w","article-title":"Functional significance of\u2002cholesterol\u2002metabolism in\u2002cancer: from threat to treatment","volume":"55","author":"Xiao","year":"2023","journal-title":"Exp Mol Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-2613","article-title":"The\u2002Role\u2002of\u2002Cholesterol\u2002in\u2002Cancer","volume":"76","author":"Kuzu","year":"2016","journal-title":"Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac822","article-title":"Elevated remnant cholesterol, plasma triglycerides, and cardiovascular and noncardiovascular mortality","volume":"44","author":"Wadstr\u00f6m","year":"2023","journal-title":"Eur Heart J"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2023.12.035","article-title":"Associations of\u2002remnant\u2002cholesterol\u2002with cardiovascular and\u2002cancer\u2002mortality in a nationwide cohort","volume":"69","author":"Tian","year":"2024","journal-title":"Sci Bull (Beijing)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac283","article-title":"Remnant\u2002Cholesterol\u2002Predicts long-term mortality of patients with metabolic dysfunction-associated fatty liver disease","volume":"107","author":"Huang","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2007.00589.x","article-title":"Discrimination of metabolic profiles of pancreatic cancer from chronic pancreatitis by high-resolution magic angle spinning 1H nuclear magnetic resonance and principal components analysis","volume":"98","author":"Fang","year":"2007","journal-title":"Cancer Sci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-016-4539-4","article-title":"Prediction of pancreatic neuroendocrine tumour grade with MR imaging features: added value of diffusion-weighted imaging","volume":"27","author":"Lotfalizadeh","year":"2017","journal-title":"Eur Radiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.hbpd.2021.12.006","article-title":"Radiomics in pancreatic cancer for oncologist: Present and future","volume":"21","author":"de la Pinta","year":"2022","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1177\/0284185117725367","article-title":"Pancreatic neuroendocrine tumor: prediction of the tumor grade using CT findings and computerized texture analysis","volume":"9","author":"Choi","year":"2018","journal-title":"Acta Radiol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.cmet.2014.01.019","article-title":"Cholesteryl ester accumulation induced by PTEN loss and PI3K\/AKT activation underlies human prostate cancer aggressiveness","volume":"19","author":"Yue","year":"2014","journal-title":"Cell Metab"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.08.011","article-title":"Anticancer activity of the cholesterol exporter ABCA1 gene","volume":"2","author":"Smith","year":"2012","journal-title":"Cell Rep"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-1756","article-title":"Obesity, cholesterol metabolism, and breast cancer pathogenesis","volume":"74","author":"McDonnell","year":"2014","journal-title":"Cancer Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5177","DOI":"10.3390\/cancers15215177","article-title":"Cholesterol\u2002Metabolism in pancreatic\u2002Cancer","volume":"15","author":"Rebelo","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0567","article-title":"Acetyl-coA metabolism supports multistep pancreatic tumorigenesis","volume":"9","author":"Carrer","year":"2019","journal-title":"Cancer Discov"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17347","article-title":"SQLE facilitates the pancreatic cancer progression via the lncRNA-TTN-AS1\/miR-133b\/SQLE axis","volume":"26","author":"Wang","year":"2022","journal-title":"J Cell Mol Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwaf037","article-title":"The role of systemic inflammation in remnant cholesterol associated cardiovascular risk: insights from the EPIC-Norfolk study","volume":"6","author":"Kraaijenhof","year":"2025","journal-title":"Eur J Prev Cardiol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-021-00752-6","article-title":"Systemic inflammation markers and cancer incidence in the UK Biobank","volume":"36","author":"N\u00f8st","year":"2021","journal-title":"Eur J Epidemiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3611","article-title":"Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms","volume":"13","author":"Elinav","year":"2013","journal-title":"Nat Rev Cancer"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1616523\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T04:12:26Z","timestamp":1756959146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1616523\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,4]]},"references-count":41,"alternative-id":["10.3389\/fendo.2025.1616523"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1616523","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2025,9,4]]},"article-number":"1616523"}}