Abstract
The CXC chemokines belong to a family which includes 17 different CXC members. Accumulating evidence suggests that CXC chemokines regulate tumor cell proliferation, invasion, and metastasis in various types of cancers by influencing the tumor microenvironment. The different expression profiles and specific function of each CXC chemokine in head and neck squamous cell carcinoma (HNSCC) are not yet clarified. In our work, we analyzed the altered expression, interaction network, and clinical data of CXC chemokines in patients with HNSCC by using the following: the Oncomine dataset, cBioPortal, Metascape, String analysis, GEPIA, and the Kaplan–Meier plotter. The transcriptional level analysis suggested that the mRNA levels of CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CXCL9, CXCL10, CXCL11, and CXCL13 increased in HNSCC tissue samples when compared to the control tissue samples. The expression levels of CXCL9, CXCL10, CXCL11, CXCL12, and CXCL14 were associated with various tumor stages in HNSCC. Clinical data analysis showed that high transcription levels of CXCL2, CXCL3, and CXCL12, were linked with low relapse-free survival (RFS) in HNSCC patients. On the other hand, high CXCL14 levels predicted high RFS outcomes in HNSCC patients. Meanwhile, increased gene transcription levels of CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 were associated with a higher overall survival (OS) advantage in HNSCC patients, while high levels of CXCL1, and CXCL8 were associated with poor OS in all HNSCC patients. This study implied that CXCL1, CXCL2, CXCL3, CXCL8, and CXCL12 could be used as prognosis markers to identify low survival rate subgroups of patients with HNSCC as well as be potential suitable therapeutic targets for HNSCC patients. Additionally, CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 could be used as functional prognosis biomarkers to identify better survival rate subgroups of patients with HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignant tumor cancer in the world and has nearly 600,000 new patients each year [1]
The results showed that the transcription levels of CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CXCL9, CXCL10, CXCL11, and CXCL13 in head and neck squamous cell carcinoma (HNSCC) samples were significantly higher than those in normal samples
We found that the transcription levels of CXCL1, CXCL8, CXCL9, CXCL10, CXCL11, and CXCL13 were remarkably upregulated in HNSCC samples when compared to normal samples
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignant tumor cancer in the world and has nearly 600,000 new patients each year [1]. Antibody drugs for the treatment of HNSCC have been developed, such as nivolumab, cetuximab, and pembrolizumab, but the 5-year survival rate is still relatively low for advanced patients [2, 3]. Chemokines are small molecules secreted by cells that play an essential role in chemotaxis and angiogenesis and are moderators of tumor initiation and metastasis [4, 5]. Homeostatic chemokines regulate cell migration and immune surveillance systems and are continuously expressed in normal tissues [7, 8]. Inflammatory chemokines are used to recruit various inflammatory cells to deal with cell damage and infection [9]
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