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SQLE——宫颈癌中一个有前景的预后生物标志物:对肿瘤恶性行为、胆固醇合成、上皮-间质转化和免疫浸润的影响

英文原题:SQLE-a promising prognostic biomarker in cervical cancer: implications for tumor malignant behavior, cholesterol synthesis, epithelial-mesenchymal transition, and immune infiltration.

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SQLE-a promising prognostic biomarker in cervical cancer: implications for tumor malignant behavior, cholesterol synthesis, epithelial-mesenchymal transition, and immune infiltration.

PubMed 2024/09/11(内容时间) BMC Cancer Q2 · IF 4.1(JCR 2025)

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研究概要

SQLE 显著影响 CESC 预后、恶性行为、胆固醇合成、EMT 和免疫浸润,从而在 CESC 中提供诊断和指标作用。因此,SQLE 可作为 CESC 治疗的新治疗靶点。

研究思路结论见上方概要

宫颈癌,包括鳞状细胞癌和宫颈内膜腺癌(CESC),对女性健康构成相当大的风险。近期研究报道,角鲨烯环氧酶(SQLE)在多种癌症中过表达,促进癌症发展。

SQLE的RNA测序数据来自癌症基因组图谱。进行了体外实验,包括比色法、集落形成、Transwell、RT-qPCR和Western blotting。此外,构建了移植性CESC裸鼠模型,以验证SQLE在体内的致瘤活性。检测了SQLE表达谱、差异表达基因(DEGs)、免疫浸润和化疗敏感性之间的关联。还评估了SQLE基因改变和DNA甲基化的预后价值。

SQLE mRNA 表达在 CESC 中显著升高。ROC 分析显示 SQLE 对 CESC 具有很强的诊断能力。SQLE 高表达患者的总体生存期较短。SQLE 对癌细胞增殖、转移、胆固醇合成和 EMT 的促进作用得到强调。DEGs 功能富集分析揭示了相关信号通路和生物学过程。值得注意的是,SQLE 表达与免疫细胞的存在以及免疫检查点的激活之间存在联系。SQLE 表达升高表现出化疗反应增强。SQLE 甲基化状态与 CESC 预后显著相关。

展开英文摘要原文

Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development.

RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed.

SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis.

SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.

论文信息

作者
Zhao YC、Li YF、Qiu L、Jin SZ、Shen YN、Zhang CH、Cui J、Wang TJ
第一作者单位
Department of Radiation Oncology, The Second Hospital of Jilin University, 218 Zi-qiang Street, Nan-guan District, Changchun, Jilin, 130041, PR China.China
通讯作者单位
Department of Radiation Oncology, The Second Hospital of Jilin University, 218 Zi-qiang Street, Nan-guan District, Changchun, Jilin, 130041, PR China. tjwang@jlu.edu.cn.China
期刊
BMC cancer2024 Sep 11
原文标识
PubMed 39261819 · DOI 10.1186/s12885-024-12897-0