Mathematical Biosciences and Engineering (Sep 2021)

Exploration of potential therapeutic and prognostic value of CXC chemokines in cervical squamous cell carcinoma and endocervical adenocarcinoma based on bioinformatics analysis

  • Caiyun Wu,
  • Cong Ma,
  • Jing Yuan,
  • Pei Zhou

DOI
https://doi.org/10.3934/mbe.2021407
Journal volume & issue
Vol. 18, no. 6
pp. 8201 – 8222

Abstract

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Cervical cancer, as the second most common female malignancy, brings a great health burden to women worldwide. Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are the most common histological subtypes of cervical cancer. CXC chemokines (CXCLs) within the tumor microenvironment can modulate carcinogenesis and progression. The present study aimed to explore the therapeutic and prognostic value of different CXCLs in CESC. ONCOMINE, GEPIA, cBioPortal, TRRUST, GeneMANIA, STRING and TIMER were utilized to explore the expression, mutation and function of CXCLs in CESC, as well as their correlation with pathological and survival features of CESC patients. We found that the mRNA expression levels of CXCL1/8/9/10/11/13/16/17 in CESC were upregulated compared with normal cervical tissues, whereas CXCL12 was downregulated. No significant correlation was found between the expression levels and pathological stage of CESC patients. CESC patients with high expression of CXCL1/2/3/4/5/8 were significantly associated with poor overall survival, additionally, low mRNA level of CXCL3 was associated with better disease-free survival. Besides, a high mutation rate (43%) of CXCLs in CESC was observed. Depicted by co-expression analysis, the expression of CXCL1/2/3/6/8 showed a modest to strong correlation, while that of CXCL9/10/11/13 showed a very strong correlation. Differentially expressed CXCLs primarily functioned in chemokine signaling pathway and inflammation response, such as cell chemotaxis, chemokine activity and chemokine receptor binding. We also found the association of CXCLs with the tumor-infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells) in CESC patients. The present study elucidated that CXCLs may have the potential to be novel therapeutic targets and prognosis predictors of CESC patients.

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