The immune landscape and prognostic analysis of CXCL8 immune-related genes in cervical squamous cell carcinoma

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES
Xiaoqian Zhang, Jian Yang, Qianqian Feng, Liping Gu, Gongzhao Qin, Chen Cheng, Shunyu Hou, Zhouhong Shi
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引用次数: 0

Abstract

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.
宫颈鳞状细胞癌中 CXCL8 免疫相关基因的免疫图谱和预后分析
宫颈鳞状细胞癌(CESC)是女性最常见的恶性肿瘤之一,给全世界妇女的健康带来了沉重负担。尽管进行了大量研究,但宫颈鳞状细胞癌和 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、免疫微环境浸润和预后,为指导临床治疗提供理论依据。首先,通过挖掘公共数据库中的四个基因组和免疫相关基因组,确定了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lasso回归分析,确定了4个与CESC无关的预后基因,并构建了预后模型,将其分为高危组和低危组。通过ssGSEA富集分析探讨了这些基因与免疫细胞和免疫功能的相关性,发现高风险组与血管生成和上皮-间质转化等过程密切相关。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的 CXCL8 表达存在显著差异。随后,研究人员构建了CXCL8基因敲除质粒,并在MEG-01和HCE-1两种CESC细胞系中验证了CXCL8基因敲除的效率。通过CCK-8、划痕和Transwell试验证实,CXCL8敲除可抑制CESC细胞的增殖、侵袭和迁移能力。以CXCL8为靶点有望用于CESC的个性化治疗,为实现临床转化提供了坚实的理论基础。
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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