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The immune landscape and prognostic analysis of CXCL8 immune‐related genes in cervical squamous cell carcinoma
Environmental Toxicology ( IF 4.5 ) Pub Date : 2024-04-10 , DOI: 10.1002/tox.24283
Xiaoqian Zhang 1 , Jian Yang 1 , Qianqian Feng 1 , Liping Gu 1 , Gongzhao Qin 1 , Chen Cheng 1 , Shunyu Hou 1 , Zhouhong Shi 1
Affiliation  

Cervical squamous cell carcinoma (CESC), one of the most common malignancies in women, imposes a significant burden on women's health worldwide. Despite extensive research, the molecular and pathogenic mechanisms of cervical squamous cell carcinoma and CESC remain unclear. This study aimed to explore the immune‐related genes, immune microenvironment infiltration, and prognosis of CESC, providing a theoretical basis for guiding clinical treatment. Initially, by mining four gene sets and immune‐related gene sets from public databases, 14 immune‐related genes associated with CESC were identified. Through univariate and multivariate COX regression analyses, as well as lasso regression analysis, four CESC‐independent prognostic genes were identified, and a prognostic model was constructed, dividing them into high and low‐risk groups. The correlation between these genes and immune cells and immune functions were explored through ssGSEA enrichment analysis, revealing a close association between the high‐risk group and processes such as angiogenesis and epithelial–mesenchymal transition. Furthermore, using public databases and qRT‐PCR experiments, significant differences in CXCL8 expression between normal cervical cells and cervical cancer cells were discovered. Subsequently, a CXCL8 knockdown plasmid was constructed, and the efficiency of CXCL8 knockdown was validated in two CESC cell lines, MEG‐01 and HCE‐1. Through CCK‐8, scratch, and Transwell assays, it was confirmed that CXCL8 knockdown could inhibit the proliferation, invasion, and migration abilities of CESC cells. Targeting CXCL8 holds promise for personalized therapy for CESC, providing a strong theoretical basis for achieving clinical translation.

中文翻译:

CXCL8免疫相关基因在宫颈鳞癌中的免疫格局及预后分析

宫颈鳞状细胞癌(CESC)是女性最常见的恶性肿瘤之一,给全世界女性的健康带来了巨大的负担。尽管进行了大量研究,宫颈鳞状细胞癌和CESC的分子和致病机制仍不清楚。本研究旨在探讨CESC的免疫相关基因、免疫微环境浸润及预后,为指导临床治疗提供理论依据。最初,通过从公共数据库中挖掘 4 个基因集和免疫相关基因集,鉴定出 14 个与 CESC 相关的免疫相关基因。通过单变量和多变量COX回归分析以及套索回归分析,确定了四个与CESC无关的预后基因,并构建了预后模型,将其分为高风险组和低风险组。通过ssGSEA富集分析探讨了这些基因与免疫细胞和免疫功能之间的相关性,揭示了高危人群与血管生成和上皮间质转化等过程之间的密切关联。此外,利用公共数据库和qRT-PCR实验,发现正常宫颈细胞和宫颈癌细胞之间CXCL8表达存在显着差异。随后,构建了CXCL8敲低质粒,并在两种CESC细胞系MEG-01和HCE-1中验证了CXCL8敲低的效率。通过CCK-8、划痕和Transwell实验,证实CXCL8敲低可以抑制CESC细胞的增殖、侵袭和迁移能力。以CXCL8为靶点有望实现CESC的个性化治疗,为实现临床转化提供强有力的理论基础。
更新日期:2024-04-10
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