{"title":"Pancreatic Cancer: An Exocrine Tumor With Endocrine Characteristics.","authors":"Xinzhe Zhu, Zhiwen Xiao, He Liu, Pin Zhang, Shengming Deng, Lei Ding, Jingjing Feng, Jianfeng Luo, Quanxing Ni, Guopei Luo, Xianjun Yu","doi":"10.1097/SLA.0000000000006168","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To examine the characteristics of patients with pancreatic cancer with long-term survival.</p><p><strong>Background: </strong>Although pancreatic cancer is a highly lethal malignancy, a minority of patients experience long-term survival. The characteristics of these patients remain largely unidentified.</p><p><strong>Methods: </strong>An indolent subgroup was established using carbohydrate antigen 19-9 (CA19-9), which is the best-validated biomarker for pancreatic cancer. Of 1558 patients, 13.9% were included in the CA19-9-normal (≤37 U/mL) subgroup.</p><p><strong>Results: </strong>A normal CA19-9 level was an independent variable for overall survival (median survival, 18.1 vs 9.7 months, hazard ratio = 0.53, P < 0.001). The 5-year survival of patients with stage IV CA19-9-normal cancer was higher than that of patients with stage I-IV CA19-9-high cancer (22.4% vs 6.8%, P = 0.034). The CA19-9-normal subgroup exhibited reduced levels of circulating glucose ( P < 0.001) and increased expression of insulin ( P < 0.001) compared with the CA19-9-high subgroup. Glucose was a substrate for CA19-9 biosynthesis through the hexosamine biosynthesis pathway. In addition, in pancreatic cancer animal models of diabetes, glucose control decreased CA19-9 levels and improved overall survival. In a clinical trial (NCT05306028) of patients before undergoing major anticancer treatments, glucose control decreased CA19-9 levels in 90.9% of the patients.</p><p><strong>Conclusions: </strong>CA19-9-normal pancreatic cancer is a strikingly indolent subgroup with low glucose and high insulin. Glucose control is a promising therapeutic strategy for pancreatic cancer.</p>","PeriodicalId":8017,"journal":{"name":"Annals of surgery","volume":null,"pages":null},"PeriodicalIF":7.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SLA.0000000000006168","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/5 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: To examine the characteristics of patients with pancreatic cancer with long-term survival.
Background: Although pancreatic cancer is a highly lethal malignancy, a minority of patients experience long-term survival. The characteristics of these patients remain largely unidentified.
Methods: An indolent subgroup was established using carbohydrate antigen 19-9 (CA19-9), which is the best-validated biomarker for pancreatic cancer. Of 1558 patients, 13.9% were included in the CA19-9-normal (≤37 U/mL) subgroup.
Results: A normal CA19-9 level was an independent variable for overall survival (median survival, 18.1 vs 9.7 months, hazard ratio = 0.53, P < 0.001). The 5-year survival of patients with stage IV CA19-9-normal cancer was higher than that of patients with stage I-IV CA19-9-high cancer (22.4% vs 6.8%, P = 0.034). The CA19-9-normal subgroup exhibited reduced levels of circulating glucose ( P < 0.001) and increased expression of insulin ( P < 0.001) compared with the CA19-9-high subgroup. Glucose was a substrate for CA19-9 biosynthesis through the hexosamine biosynthesis pathway. In addition, in pancreatic cancer animal models of diabetes, glucose control decreased CA19-9 levels and improved overall survival. In a clinical trial (NCT05306028) of patients before undergoing major anticancer treatments, glucose control decreased CA19-9 levels in 90.9% of the patients.
Conclusions: CA19-9-normal pancreatic cancer is a strikingly indolent subgroup with low glucose and high insulin. Glucose control is a promising therapeutic strategy for pancreatic cancer.
期刊介绍:
The Annals of Surgery is a renowned surgery journal, recognized globally for its extensive scholarly references. It serves as a valuable resource for the international medical community by disseminating knowledge regarding important developments in surgical science and practice. Surgeons regularly turn to the Annals of Surgery to stay updated on innovative practices and techniques. The journal also offers special editorial features such as "Advances in Surgical Technique," offering timely coverage of ongoing clinical issues. Additionally, the journal publishes monthly review articles that address the latest concerns in surgical practice.