Liu Bo, Huang Rongfei, Fu Tingting, He Ping, Du Chengyou, Zhou Wei, Xu Ke, Ren Tao
Department of Hepatobiliary Surgery, Pidu District People's Hospital of Chengdu, Chengdu, China.
Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Chengdu Medical College, Chengdu, China.
PeerJ. 2021 May 11;9:e11423. doi: 10.7717/peerj.11423. eCollection 2021.
Pancreatic adenocarcinoma (PAAD) is a disease with atypical symptoms, an unfavorable response to therapy, and a poor outcome. Abnormal guanylate-binding proteins (GBPs) play an important role in the host's defense against viral infection and may be related to carcinogenesis. In this study, we sought to determine the relationship between GBP2 expression and phenotype in patients with PAAD and explored the possible underlying biological mechanism.
We analyzed the expression of GBP2 in PAAD tissues using a multiple gene expression database and a cohort of 42 PAAD patients. We evaluated GBP2's prognostic value using Kaplan-Meier analysis and the Cox regression model. GO and KEGG enrichment analysis, co-expression analysis, and GSEA were performed to illustrate the possible underlying biological mechanism. CIBERSORT and the relative expression of immune checkpoints were used to estimate the relationship between GBP2 expression and tumor immunology.
GBP2 was remarkably overexpressed in PAAD tissue. The overexpression of GBP2 was correlated with an advanced T stage and poor overall survival (OS) and GBP2 expression was an independent risk factor for OS in PAAD patients. Functional analysis demonstrated that positively co-expressed genes of GBP2 were closely associated with pathways in cancer and the NOD-like receptor signaling pathway. Most of the characteristic immune checkpoints, including PDCD1, PDCDL1, CTLA4, CD80, TIGIT, LAG3, IDO2, and VISTA, were significantly expressed in the high-GBP2 expression group compared with the low-GBP2 expression group.
GBP2 acted as a potential prognostic biomarker and was associated with immune infiltration and the expression of immune checkpoints in PAAD.
胰腺腺癌（PAAD）是一种症状不典型、治疗反应不佳且预后不良的疾病。异常的鸟苷酸结合蛋白（GBP）在宿主抵御病毒感染中起重要作用，可能与肿瘤发生有关。在本研究中，我们试图确定PAAD患者中GBP2表达与表型之间的关系，并探索可能的潜在生物学机制。
我们使用多基因表达数据库和42例PAAD患者队列分析了PAAD组织中GBP2的表达。我们使用Kaplan-Meier分析和Cox回归模型评估GBP2的预后价值。进行GO和KEGG富集分析、共表达分析和GSEA以阐明可能的潜在生物学机制。使用CIBERSORT和免疫检查点的相对表达来估计GBP2表达与肿瘤免疫学之间的关系。
GBP2在PAAD组织中显著过表达。GBP2的过表达与晚期T分期和较差的总生存期（OS）相关，并且GBP2表达是PAAD患者OS的独立危险因素。功能分析表明，GBP2的正共表达基因与癌症通路和NOD样受体信号通路密切相关。与低GBP2表达组相比，包括PDCD1、PDCDL1、CTLA4、CD80、TIGIT、LAG3、IDO2和VISTA在内的大多数特征性免疫检查点在高GBP2表达组中显著表达。
GBP2作为一种潜在的预后生物标志物，与PAAD中的免疫浸润和免疫检查点表达相关。
