Molecular mechanisms of thymopoietin in papillary thyroid cancer: Multiplatform gene expression data, gene knockout screening, and in-house immunohistochemistry.

IF 3.2 Q3 ONCOLOGY
Chang Song, Yu-Yan Pang, Shang-Yi Lu, Bin Li, Dong-Ming Li, Rong-Quan He, Di-Yuan Qin, Shi-De Li, Ning Qv, Yan-Mei Chen, Gang Chen, Juan He, Xiao-Bo Jiang
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引用次数: 0

Abstract

Background: Although thymopoietin (TMPO) has been elucidated to be overexpressed in cancers, its underlying mechanisms are not yet fully understood.

Aim: To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma (PTC).

Methods: Databases such as Gene Expression Omnibus, The Cancer Genome Atlas Program-Genotype-Tissue Expression, The Human Protein Atlas (THPA), and tissue microarrays were screened. Immunohistochemical staining scores and standardized mean difference were used to calculate expression levels, and summary receiver operating characteristic curves were plotted to evaluate diagnostic performance. A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways. A protein interaction network was constructed to identify hub genes. The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats (CRISPR) knockout screening and the Cancer Cell Line Encyclopedia database.

Results: The TMPO protein was significantly overexpressed in PTC tissues, primarily localized in the cytoplasm and nuclear membrane. The mRNA level analysis showed mild overexpression of TMPO in PTC tissues, with a certain discriminatory value (area under the curve = 0.66). TMPO may promote cancer through involvement in cell adhesion, focal adhesion, leukocyte migration, and multiple cancer-related signaling pathways. Additionally, CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines, indicating its important role in tumor growth.

Conclusion: TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.

甲状腺乳头状癌中促甲状腺生成素的分子机制:多平台基因表达数据、基因敲除筛选和内部免疫组织化学。
背景:虽然已证实胸腺生成素(thymopoietin, TMPO)在癌症中过度表达,但其潜在机制尚未完全清楚。目的:探讨TMPO在甲状腺乳头状癌(PTC)中的表达及临床意义。方法:筛选基因表达Omnibus、Cancer Genome Atlas program -基因型-组织表达、Human Protein Atlas (THPA)和组织芯片等数据库。使用免疫组织化学染色评分和标准化平均差来计算表达水平,并绘制总结受试者工作特征曲线以评估诊断性能。基因集富集分析富集分析确定tmpo相关信号通路。构建了蛋白相互作用网络,对枢纽基因进行了识别。利用聚类规则间隔短回文重复序列(CRISPR)敲除筛选和Cancer cell Line Encyclopedia数据库分析TMPO对PTC细胞增殖的影响及其敲除效果。结果:TMPO蛋白在PTC组织中显著过表达,主要定位于细胞质和核膜。mRNA水平分析显示,TMPO在PTC组织中轻度过表达,具有一定的判别值(曲线下面积= 0.66)。TMPO可能通过参与细胞粘附、局灶粘附、白细胞迁移和多种癌症相关信号通路来促进癌症。此外,CRISPR基因敲除实验证实,敲除TMPO可显著抑制PTC细胞系的增殖,提示其在肿瘤生长中的重要作用。结论:TMPO在PTC中过表达,可能作为PTC的治疗靶点和分子生物标志物。
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来源期刊
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585
期刊介绍: The WJCO is a high-quality, peer reviewed, open-access journal. The primary task of WJCO is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of oncology. In order to promote productive academic communication, the peer review process for the WJCO is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJCO are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in oncology. Scope: Art of Oncology, Biology of Neoplasia, Breast Cancer, Cancer Prevention and Control, Cancer-Related Complications, Diagnosis in Oncology, Gastrointestinal Cancer, Genetic Testing For Cancer, Gynecologic Cancer, Head and Neck Cancer, Hematologic Malignancy, Lung Cancer, Melanoma, Molecular Oncology, Neurooncology, Palliative and Supportive Care, Pediatric Oncology, Surgical Oncology, Translational Oncology, and Urologic Oncology.
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