From the Department of General Surgery, Guangdong Provincial People's Hospital, GuangdongAcademy of Medical Sciences, Guangzhou, China.
Pancreas. 2022 Oct 1;51(9):1235-1247. doi: 10.1097/MPA.0000000000002178.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by occult onset, rapid progression, and poor prognosis. CXC chemokines play an important role in tumor microenvironment and development. However, the potential mechanistic values of CXC chemokines as clinical biomarkers and therapeutic targets in PDAC have not been fully clarified.
The altered expression, interaction network, and clinical data of CXC chemokines in patients with PDAC were analyzed by the data from the Gene Expression Omnibus and the Tumor Cancer Genome Atlas.
CXCL5 transcriptional level was significantly elevated in PDAC tissues. A significant correlation was found between the expression of CXC1/3/5/8 and the pathological stage of PDAC patients. The PDAC patients with low transcriptional levels of CXCL5/9/10/11/17 were associated with a significantly better prognosis. The functions of differentially expressed CXC chemokines are primarily related to the chemokine signaling pathway, cytokine-cytokine receptor interaction, and viral protein interaction with cytokine and cytokine receptor. RELA, NFKB1, and SP1 are key transcription factors for CXC chemokines, and the SRC family of tyrosine kinases, mitogen-activated protein kinases, CDK5, PRKCQ, ROCK1, ITK, IKBKE, JAK3, and NTRK2 are CXC chemokine targets.
The results indicated that CXC chemokines might serve as therapeutic targets and prognostic biomarkers in PDAC.
胰腺导管腺癌 (PDAC) 的特点是隐匿发病、进展迅速、预后不良。CXC 趋化因子在肿瘤微环境和发展中发挥着重要作用。然而，CXC 趋化因子作为 PDAC 的临床生物标志物和治疗靶点的潜在机制价值尚未得到充分阐明。
通过基因表达综合数据库和肿瘤基因组图谱中的数据，分析 PDAC 患者中 CXC 趋化因子的改变表达、相互作用网络和临床数据。
CXCL5 的转录水平在 PDAC 组织中显著升高。CXC1/3/5/8 的表达与 PDAC 患者的病理分期之间存在显著相关性。CXCL5/9/10/11/17 转录水平较低的 PDAC 患者预后明显更好。差异表达的 CXC 趋化因子的功能主要与趋化因子信号通路、细胞因子-细胞因子受体相互作用以及病毒蛋白与细胞因子和细胞因子受体的相互作用有关。RELA、NFKB1 和 SP1 是 CXC 趋化因子的关键转录因子，而 SRC 家族酪氨酸激酶、丝裂原活化蛋白激酶、CDK5、PRKCQ、ROCK1、ITK、IKBKE、JAK3 和 NTRK2 是 CXC 趋化因子的靶点。
结果表明，CXC 趋化因子可能作为 PDAC 的治疗靶点和预后生物标志物。
