Pancreatic Cancer
Pancreatic Cancer
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DOI：
10.1097/sla.0000000000006168
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发表时间：
2024-12-01
影响因子：
9
通讯作者：
Yu，Xianjun
中科院分区：
文献类型：
--
作者：
Zhu，Xinzhe;Xiao，Zhiwen;Yu，Xianjun
目的：探讨胰腺癌患者长期生存的特点。背景：虽然胰腺癌是一种高致命性的恶性肿瘤，但少数患者有长期生存的经历。这些患者的特征在很大程度上仍不清楚。方法：利用糖类抗原19-9(CA19-9)建立了一个惰性亚群，CA19-9是最有效的胰腺癌生物标志物。结果：CA19-9水平正常是影响患者总生存期的一个独立变量(中位生存期18.1月对9.7月，风险比=0.53P&0.001)。第IV期CA19-9-正常癌患者的5年生存率高于第I-IV期CA19-9-高癌组(22.4%vs6.8%，P=0.034)。与CA19-9高表达亚组相比，CA19-9正常亚组的循环血糖水平降低(P<；0.001)，胰岛素表达增加(P<；0.001)。葡萄糖是通过己糖胺生物合成途径合成CA19-9的底物。此外，在糖尿病的胰腺癌动物模型中，血糖控制降低了CA19-9水平，提高了总体存活率。在一项对接受主要抗癌治疗的患者进行的临床试验(NCT05306028)中，90.9%的患者在接受主要抗癌治疗之前，血糖控制降低了CA19-9水平。结论：CA19-9-正常的胰腺癌是一个显著的惰性亚群，具有低血糖和高胰岛素的特点。控制血糖是治疗胰腺癌的一种很有前途的治疗策略。
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.