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丝氨酸蛋白酶抑制剂B7作为宫颈癌的预后生物标志物:与免疫浸润及恶性表型促进作用的关联

SERPINB7 as a prognostic biomarker in cervical cancer: Association with immune infiltration and facilitation of the malignant phenotype.

作者信息

Wei Hua-Fang, Zhang Rui-Feng, Zhao Yue-Chen, Tong Xian-Shuang

机构信息

Department of Internal Medicine-1, Jilin Cancer Hospital, Changchun, Jilin, People's Republic of China.

Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China.

出版信息

Heliyon. 2023 Sep 15;9(9):e20184. doi: 10.1016/j.heliyon.2023.e20184. eCollection 2023 Sep.

Abstract

PURPOSE

The purpose of this study was to investigate the expression patterns, predictive significance, and roles in the immune microenvironment of Serpin Family-B Member 7 (SERPINB7) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).

METHODS

The expression of SERPINB7 and its prognostic relevance were evaluated using RNA-seq data from The Cancer Genome Atlas. SERPINB7 regulation of CESC cell growth and metastasis was investigated using MTT, scratch, and Transwell assays. effects of SERPINB7 were examined in xenograft model mice and differentially expressed genes (DEGs) associated with SERPINB7 were identified to explore its functional role in oncogenesis. Associations between SERPINB7 levels, chemosensitivity, and immune infiltration were assessed, and mutations and methylation of SERPINB7 were evaluated using the cBioPortal and MethSurv databases, respectively.

RESULTS

SERPINB7 was up-regulated in CESC samples as well as in other tumors, and patients with higher SERPINB7A mRNA levels exhibited shorter overall survival. The area under the curve for the use of SERPINB7 in CESC diagnosis was above 0.9, and the gene was shown to regulate tumor cell proliferation and metastasis and . Overall, 398 DEGs enriched in key CESC progression-related signaling pathways were identified. SERPINB7 expression was additionally correlated with intratumoral immune infiltration and immune checkpoint activity. Patients expressing higher SERPINB7 levels exhibited distinct chemosensitivity profiles, and methylation of the SERPINB7 gene was linked to CESC patient prognostic outcomes.

CONCLUSION

SERPINB7 was found to be a crucial regulator of CESC progression, prognosis, and the tumor immune microenvironment, highlighting its potential as a diagnostic and prognostic biomarker and target for CESC immunotherapy.

摘要

目的

本研究旨在探讨丝氨酸蛋白酶抑制剂家族B成员7(SERPINB7)在宫颈鳞状细胞癌和宫颈内膜腺癌(CESC)中的表达模式、预测意义及其在免疫微环境中的作用。

方法

利用来自癌症基因组图谱的RNA测序数据评估SERPINB7的表达及其预后相关性。采用MTT、划痕和Transwell实验研究SERPINB7对CESC细胞生长和转移的调控作用。在异种移植模型小鼠中检测SERPINB7的作用,并鉴定与SERPINB7相关的差异表达基因(DEG),以探索其在肿瘤发生中的功能作用。评估SERPINB7水平、化疗敏感性和免疫浸润之间的关联,并分别使用cBioPortal和MethSurv数据库评估SERPINB7的突变和甲基化情况。

结果

SERPINB7在CESC样本以及其他肿瘤中上调,SERPINB7A mRNA水平较高的患者总生存期较短。SERPINB7用于CESC诊断的曲线下面积大于0.9,该基因被证明可调节肿瘤细胞增殖和转移。总体而言,共鉴定出398个富集于关键CESC进展相关信号通路的DEG。SERPINB7表达还与肿瘤内免疫浸润和免疫检查点活性相关。表达较高SERPINB7水平的患者表现出不同的化疗敏感性特征,SERPINB7基因的甲基化与CESC患者的预后结果相关。

结论

发现SERPINB7是CESC进展、预后和肿瘤免疫微环境的关键调节因子,突出了其作为CESC诊断和预后生物标志物以及免疫治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c46b/10559959/03765e352280/gr1.jpg

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