CXCL10是胰腺腺癌中一种与肿瘤微环境和免疫浸润相关的预后生物标志物。

CXCL10 is a Tumor Microenvironment and Immune Infiltration Related Prognostic Biomarker in Pancreatic Adenocarcinoma.

作者信息

Huang Huimin, Zhou Wangxiao, Chen Renpin, Xiang Bingfeng, Zhou Shipeng, Lan Linhua

机构信息

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Front Mol Biosci. 2021 Feb 18;8:611508. doi: 10.3389/fmolb.2021.611508. eCollection 2021.

Abstract

Pancreatic adenocarcinoma (PAAD) is the 10th most common cancer worldwide and the outcomes for patients with the disease remain extremely poor. Precision biomarkers are urgently needed to increase the efficiency of early diagnosis and to improve the prognosis of patients. The tumor microenvironment (TME) and tumor immune infiltration are thought to impact the occurrence, progression, and prognosis of PAAD. Novel biomarkers excavated originating from the TME and immune infiltration may be effective in predicting the prognosis of PAAD patients. In the current study, the ESTIMATE and CIBERSORT algorithms were applied to estimate the division of immune and stromal components and the proportion of tumor-infiltrating immune cells in 182 PAAD cases downloaded from The Cancer Genome Atlas database. Intersection analyses of the Protein-Protein Interaction networks and Cox regression analysis identified the chemokine (CXC-motif) ligand 10 (CXCL10) as a predictive biomarker. We verified that CXCL10 in the TME negatively correlates with prognosis in PAAD and positively correlates with tumor cell differentiation. GSE62452 from the GEO database and cumulative survival analysis were performed to validate CXCL10 expression as an independent prognostic indicator. We also found that memory B cells, regulatory T cells, and macrophages M0 and M1 were correlated with the expression of CXCL10 indicating that expression of CXCL10 influenced the immune activity of the TME. Our data suggest that CXCL10 is beneficial as a prognostic indicator in PAAD patients and highlights the potential for immune targeted therapy in the treatment of PAAD.

摘要

胰腺腺癌(PAAD)是全球第10大常见癌症,该疾病患者的预后仍然极差。迫切需要精准的生物标志物来提高早期诊断效率并改善患者预后。肿瘤微环境(TME)和肿瘤免疫浸润被认为会影响PAAD的发生、进展和预后。从TME和免疫浸润中挖掘出的新型生物标志物可能有助于预测PAAD患者的预后。在本研究中,应用ESTIMATE和CIBERSORT算法来估计从癌症基因组图谱数据库下载的182例PAAD病例中的免疫和基质成分划分以及肿瘤浸润免疫细胞的比例。通过蛋白质-蛋白质相互作用网络的交集分析和Cox回归分析,确定趋化因子(CXC基序)配体10(CXCL10)为一种预测性生物标志物。我们证实,TME中的CXCL10与PAAD的预后呈负相关,与肿瘤细胞分化呈正相关。利用来自GEO数据库的GSE62452和累积生存分析来验证CXCL10表达作为独立预后指标的作用。我们还发现,记忆B细胞、调节性T细胞以及巨噬细胞M0和M1与CXCL10的表达相关,这表明CXCL10的表达影响了TME的免疫活性。我们的数据表明,CXCL10作为PAAD患者的预后指标具有重要意义,并凸显了免疫靶向治疗在PAAD治疗中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7779/7930611/9ce048ba6d9e/fmolb-08-611508-g001.jpg

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