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Updated: Jul 9, 2025

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
Published on: April 11, 2025
Pancreatic Cancer: An Exocrine Tumor With Endocrine Characteristics
Xinzhe Zhu1,2,3,4, Zhiwen Xiao1,2,3,4, He Liu1,2,3,4
1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China.
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.
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