Wu Qiong-Yuan, Yang Cheng-Kun, Rong Liang-Jun, Li Jun-Chan, Lei Long-Ming
Department of Tuina, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi 530023, P.R.China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530023, P.R.China.
Oncol Lett. 2020 Oct;20(4):16. doi: 10.3892/ol.2020.11877. Epub 2020 Jul 16.
Pancreatic ductal adenocarcinoma (PDAC) is one of the malignancies with the highest morality rate due to postoperative local invasion and distant metastasis. Although C-X-C motif chemokine receptor (CXCR) subunits have been reported as prognostic indicators in gastric cancer, the prognostic value of CXCR subunits in PDAC remains poorly understood. In the present study, the expression levels and biological functions of CXCR subunits were investigated using multiple publicly accessible bioinformatic platforms and databases. Survival analysis was used to evaluate the prognostic value of CXCR subunits in 112 early-stage PDAC cases by setting the median expression levels as the cut-off values. A nomogram was constructed to combine CXCR subunit expression levels and clinical data for prognosis prediction. Moreover, the association between CXCR subunit expression levels and tumor infiltration levels were detected in PDAC. The expression levels of CXCR subunits were elevated in PDAC tumor tissues. In the multivariate Cox proportional risk regression model, high CXCR2, CXCR4 and CXCR6 expression levels in early-stage PDAC were associated with a more favorable prognosis. Further, it was demonstrated that the differential expression levels of CXCR subunits in PDAC for combined survival analysis could contribute to risk stratification. The nomogram model demonstrated the contribution of CXCR subunits and clinical features in the prognosis of PDAC. Gene Set Enrichment Analysis suggested that CXCR subunits serve a role in immunomodulatory functions. The expression levels and somatic copy number alterations of CXCR subunits were associated with tumor infiltration levels in PDAC. CXCR subunits were associated with prognosis in patients with early-stage PDAC and may be potential drug targets for the treatment of pancreatic cancer.
胰腺导管腺癌（PDAC）是因术后局部侵袭和远处转移导致死亡率最高的恶性肿瘤之一。尽管C-X-C基序趋化因子受体（CXCR）亚基已被报道为胃癌的预后指标，但CXCR亚基在PDAC中的预后价值仍知之甚少。在本研究中，利用多个公开可用的生物信息学平台和数据库对CXCR亚基的表达水平和生物学功能进行了研究。通过将中位表达水平设定为临界值，采用生存分析评估CXCR亚基在112例早期PDAC病例中的预后价值。构建了一个列线图，将CXCR亚基表达水平与临床数据相结合以进行预后预测。此外，还检测了PDAC中CXCR亚基表达水平与肿瘤浸润水平之间的关联。PDAC肿瘤组织中CXCR亚基的表达水平升高。在多变量Cox比例风险回归模型中，早期PDAC中CXCR2、CXCR4和CXCR6的高表达水平与更有利的预后相关。此外，还证明了PDAC中CXCR亚基的差异表达水平用于联合生存分析有助于风险分层。列线图模型显示了CXCR亚基和临床特征在PDAC预后中的作用。基因集富集分析表明，CXCR亚基在免疫调节功能中发挥作用。CXCR亚基的表达水平和体细胞拷贝数改变与PDAC中的肿瘤浸润水平相关。CXCR亚基与早期PDAC患者的预后相关，可能是治疗胰腺癌的潜在药物靶点。
