KRT7过表达与胰腺腺癌患者的不良预后和免疫细胞浸润相关。
KRT7 Overexpression is Associated with Poor Prognosis and Immune Cell Infiltration in Patients with Pancreatic Adenocarcinoma.
作者信息
Li Yuexian, Su Zhou, Wei Biwei, Liang Zhihai
机构信息
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
出版信息
Int J Gen Med. 2021 Jun 21;14:2677-2694. doi: 10.2147/IJGM.S313584. eCollection 2021.
BACKGROUND
Pancreatic adenocarcinoma (PAAD) is a deadly tumor with a high recurrence rate and poor prognosis. Keratin 7 (KRT7) is a member of the keratin gene family that is involved in the regulation of cell growth, migration and apoptosis in many cancers. However, the role of KRT7 and its biological functions in PAAD remain unclear. We systemically analyzed the expression and clinical values of KRT7 in PAAD.
METHODS
The Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Human Protein Atlas (HPA) databases were used to analyze the mRNA and protein expression of KRT7 in PAAD. The prognosis and subgroup analysis of KRT7 in PAAD patients was performed using the GEPIA, PROGgeneV2 and UALCAN databases. Later, the correlation between KRT7 expression and tumor immune molecules in PAAD was evaluated using the Immune Cell Abundance Identifier (ImmuCellAI) and TISIDB databases. Finally, the functional enrichment pathway of KRT7 and its coexpressed genes were analyzed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape databases and Gene Set Enrichment Analysis (GSEA).
RESULTS
The mRNA and protein expression of KRT7 was increased in PAAD tissues compared with normal tissues. High KRT7 expression was closely associated with tumor grade, TP53 mutations and poor prognosis in PAAD patients. Cox regression analysis proved that overexpressed KRT7 was an important and independent risk factor for poor overall survival (P = 0.006, HR =1.87) and disease-free survival (P = 0.019, HR =1.793) in PAAD. Additionally, KRT7 expression was significantly associated with immune infiltration of tumor immune cells and immunomodulators. Functional enrichment analyses and GSEA indicated that KRT7 might be involved in the regulation of the p53 pathway in PAAD.
CONCLUSION
Overexpressed KRT7 could be a promising prognostic and therapeutic target biomarker for PAAD by bioinformatics analysis.
背景
胰腺腺癌（PAAD）是一种致命性肿瘤，复发率高且预后较差。角蛋白7（KRT7）是角蛋白基因家族的成员，在许多癌症中参与细胞生长、迁移和凋亡的调控。然而，KRT7在PAAD中的作用及其生物学功能仍不清楚。我们系统地分析了KRT7在PAAD中的表达及临床价值。
方法
使用基因表达谱交互式分析（GEPIA）、Oncomine和人类蛋白质图谱（HPA）数据库分析KRT7在PAAD中的mRNA和蛋白质表达。使用GEPIA、PROGgeneV2和UALCAN数据库对PAAD患者中KRT7进行预后及亚组分析。随后，使用免疫细胞丰度标识符（ImmuCellAI）和TISIDB数据库评估KRT7表达与PAAD中肿瘤免疫分子之间的相关性。最后，通过注释、可视化和综合发现数据库（DAVID）、Metascape数据库以及基因集富集分析（GSEA）分析KRT7及其共表达基因的功能富集途径。
结果
与正常组织相比，PAAD组织中KRT7的mRNA和蛋白质表达增加。KRT7高表达与PAAD患者的肿瘤分级、TP53突变及预后不良密切相关。Cox回归分析证明，KRT7过表达是PAAD患者总生存期差（P = 0.006，HR = 1.87）和无病生存期差（P = 0.019，HR = 1.793）的重要独立危险因素。此外，KRT7表达与肿瘤免疫细胞和免疫调节剂的免疫浸润显著相关。功能富集分析和GSEA表明，KRT7可能参与PAAD中p53途径的调控。
结论
通过生物信息学分析，KRT7过表达可能是PAAD有前景的预后和治疗靶点生物标志物。
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