Feng Zengyu, Li Kexian, Wu Yulian, Peng Chenghong
Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Mol Biosci. 2021 Mar 23;8:659168. doi: 10.3389/fmolb.2021.659168. eCollection 2021.
Accumulating evidence shows that the elevated expression of DCBLD2 (discoidin, CUB and LCCL domain-containing protein 2) is associated with unfavorable prognosis of various cancers. However, the correlation of DCBLD2 expression value with the diagnosis and prognosis of pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated.
Univariate Cox regression analysis was used to screen robust survival-related genes. Expression pattern of selected genes was investigated in PDAC tissues and normal tissues from multiple cohorts. Kaplan-Meier (K-M) survival curves, ROC curves and calibration curves were employed to assess prognostic performance. The relationship between DCBLD2 expression and immune cell infiltrates was conducted by CIBERSORT software. Biological processes and KEGG pathway enrichment analyses were adopted to clarify the potential function of DCBLD2 in PDAC.
Univariate analysis, K-M survival curves and calibration curves indicated that DCBLD2 was a robust prognostic factor for PDAC with cross-cohort compatibility. Upregulation of DCBLD2 was observed in dissected PDAC tissues as well as extracellular vesicles from both plasma and serum samples of PDAC patients. Both DCBLD2 expression in tissue and extracellular vesicles had significant diagnostic value. Besides, DCBLD2 expression was correlated with infiltrating level of CD8 T cells and macrophage M2 cells. Functional enrichment revealed that DCBLD2 might be involved in cell motility, angiogenesis, and cancer-associated pathways.
Our study systematically analyzed the potential diagnostic, prognostic and therapeutic value of DCBLD2 in PDAC. All the findings indicated that DCBLD2 might play a considerably oncogenic role in PDAC with diagnostic, prognostic and therapeutic potential. These preliminary results of bioinformatics analyses need to be further validated in more prospective studies.
越来越多的证据表明，DCBLD2（含盘状结构域、CUB结构域和LCCL结构域蛋白2）的表达升高与多种癌症的不良预后相关。然而，DCBLD2表达值与胰腺导管腺癌（PDAC）的诊断和预后之间的相关性尚未阐明。
采用单因素Cox回归分析筛选与生存相关的稳健基因。在多个队列的PDAC组织和正常组织中研究所选基因的表达模式。采用Kaplan-Meier（K-M）生存曲线、ROC曲线和校准曲线评估预后性能。通过CIBERSORT软件分析DCBLD2表达与免疫细胞浸润之间的关系。采用生物学过程和KEGG通路富集分析来阐明DCBLD2在PDAC中的潜在功能。
单因素分析、K-M生存曲线和校准曲线表明，DCBLD2是PDAC的一个具有跨队列一致性的稳健预后因素。在解剖的PDAC组织以及PDAC患者血浆和血清样本的细胞外囊泡中均观察到DCBLD2的上调。组织和细胞外囊泡中的DCBLD2表达均具有显著的诊断价值。此外，DCBLD2表达与CD8 T细胞和巨噬细胞M2细胞的浸润水平相关。功能富集分析显示，DCBLD2可能参与细胞运动、血管生成和癌症相关通路。
我们的研究系统分析了DCBLD2在PDAC中的潜在诊断、预后和治疗价值。所有结果表明，DCBLD2可能在PDAC中发挥相当大的致癌作用，具有诊断、预后和治疗潜力。这些生物信息学分析的初步结果需要在更多前瞻性研究中进一步验证。
