Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer Med. 2020 Mar;9(6):2153-2159. doi: 10.1002/cam4.2895. Epub 2020 Feb 3.
Kras mutation and abnormal immune status are associated with pancreatic cancer development and progression. In this study, we evaluated the Kras mutation status in circulating tumor DNA and circulating T cell subsets in a cohort of advanced pancreatic cancer patients.
Samples were retrospectively obtained from a series of 210 pathological advanced pancreatic cancer patients between 2012 and 2014. The Kras mutation status was detected in cell-free circulating tumor DNA (ctDNA) by ddPCR and circulating T cell subsets were analyzed by flow cytometry.
Univariate analysis found that tumor node metastasis (TNM) stage, chemotherapy, circulating regulatory T cells, CA19-9 levels, CA125 levels, and Kras and Kras mutations were significantly related to overall survival in advanced pancreatic cancer patients. Multivariate analysis identified that TNM stage (P = .03, HR:1.422), Tregs (P = .004, HR:1.522), CA19-9 levels (P = .009, HR:1.488), Kras mutation (P = .044, HR:1.353), and Kras mutation (P = .001, HR:1.667) were independent prognostic markers. Furthermore, we found that Kras mutation in ctDNA was correlated with high circulating proportion of Tregs, and patients with both Kras mutation and high levels of Tregs were associated with extremely poor survival in advanced pancreatic cancer.
Kras mutation was associated with high circulating regulatory T cell levels, and both of them predicted worse prognosis in advanced pancreatic cancer patients.
Kras 突变和异常免疫状态与胰腺癌的发生和发展有关。在本研究中，我们评估了循环肿瘤 DNA 中 Kras 突变状态和循环 T 细胞亚群在一组晚期胰腺癌患者中的情况。
本研究回顾性分析了 2012 年至 2014 年间 210 例经病理证实的晚期胰腺癌患者的样本。通过 ddPCR 检测无细胞循环肿瘤 DNA（ctDNA）中的 Kras 突变状态，通过流式细胞术分析循环 T 细胞亚群。
单因素分析发现，肿瘤淋巴结转移（TNM）分期、化疗、循环调节性 T 细胞、CA19-9 水平、CA125 水平以及 Kras 和 Kras 突变与晚期胰腺癌患者的总生存期显著相关。多因素分析确定 TNM 分期（P=0.03，HR：1.422）、Tregs（P=0.004，HR：1.522）、CA19-9 水平（P=0.009，HR：1.488）、Kras 突变（P=0.044，HR：1.353）和 Kras 突变（P=0.001，HR：1.667）是独立的预后标志物。此外，我们发现 ctDNA 中的 Kras 突变与循环 Tregs 比例升高相关，且同时存在 Kras 突变和高水平 Tregs 的患者在晚期胰腺癌中预后极差。
Kras 突变与循环调节性 T 细胞水平升高有关，两者均预示晚期胰腺癌患者预后不良。
