Reproductive Medicine Center, Department of Obstetrics and Gynecology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Math Biosci Eng. 2021 Sep 18;18(6):8201-8222. doi: 10.3934/mbe.2021407.
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.
宫颈癌是全球女性第二大常见的恶性肿瘤，给女性健康带来了巨大的负担。宫颈鳞状细胞癌和宫颈内膜腺癌（CESC）是宫颈癌最常见的组织学亚型。肿瘤微环境中的 CXC 趋化因子（CXCLs）可以调节癌症的发生和发展。本研究旨在探讨不同 CXCLs 在 CESC 中的治疗和预后价值。利用 ONCOMINE、GEPIA、cBioPortal、TRRUST、GeneMANIA、STRING 和 TIMER 探讨了 CXCLs 在 CESC 中的表达、突变和功能，以及它们与 CESC 患者的病理和生存特征的相关性。我们发现，与正常宫颈组织相比，CESC 中 CXCL1/8/9/10/11/13/16/17 的 mRNA 表达水平上调，而 CXCL12 下调。CXCLs 的表达水平与 CESC 患者的病理分期无显著相关性。CXCL1/2/3/4/5/8 高表达的 CESC 患者总生存率明显较差，此外，CXCL3 的低 mRNA 水平与无病生存率较好相关。此外，在 CESC 中观察到 CXCLs 的高突变率（43%）。通过共表达分析表明，CXCL1/2/3/6/8 的表达呈中等至强相关性，而 CXCL9/10/11/13 的表达呈很强的相关性。差异表达的 CXCLs 主要在趋化因子信号通路和炎症反应中发挥作用，如细胞趋化、趋化因子活性和趋化因子受体结合。我们还发现，在 CESC 患者中，CXCLs 与六种类型免疫细胞（B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞）的肿瘤浸润有关。本研究表明，CXCLs 可能具有成为 CESC 患者新的治疗靶点和预后预测因子的潜力。
