Zhao Yue-Chen, Wang Tie-Jun, Qu Geng-Hui, She Li-Zhen, Cui Jie, Zhang Rui-Feng, Qu Hong-Dao
Department of Radiation Oncology, The Second Hospital of Jilin University Changchun 130041, Jilin, P. R. China.
Department of Radiology, Dongliao County People's Hospital Liaoyuan 136299, Jilin, P. R. China.
Am J Cancer Res. 2023 Jul 15;13(7):3123-3139. eCollection 2023.
Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) has become increasingly prevalent in younger women. Tropomyosin 3 (TPM3), a thin filament actin-binding protein, has been implicated in various malignancies. In this study, TPM3 expression was evaluated using RNA-seq data from The Cancer Genome Atlas (TCGA), and its relationship with CESC prognosis was examined with receiver operating characteristic (ROC) curves. The effects of TPM3 on cellular proliferation and migration were examined in CESC cell lines using Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays, while effects were assessed in mouse xenograft models. Furthermore, differentially expressed genes (DEGs) associated with TPM3 were investigated to determine their tumorigenic functions. Associations between TPM3, chemosensitivity, and immune infiltration were analyzed, as were links between mutations, methylation, and prognosis using the cBioPortal and MethSurv databases. Upregulation of TMP3 mRNA and protein levels was observed in CESC samples, with elevated mRNA levels associated with reduced overall survival. TPM3 showed an area under the curve (AUC) of 0.946 for CESC diagnosis and was found to regulate tumor proliferation and metastasis and . Overall, 3099 DEGs were identified and found to be enriched in key CESC progression-related signaling pathways. TPM3 expression was also correlated with intratumoral immune cell infiltration and immune checkpoint activity. Patients with higher TPM3 expression showed distinctive chemosensitivity profiles, and TPM3 gene methylation was linked to poorer CESC patient prognostic outcomes. In conclusion, TPM3 is a key regulator of CESC progression, prognosis, and the tumor immune microenvironment, suggesting its potential as a diagnostic or prognostic biomarker and target for CESC immunotherapy.
宫颈鳞状细胞癌和宫颈管腺癌（CESC）在年轻女性中越来越普遍。原肌球蛋白3（TPM3）是一种细肌丝肌动蛋白结合蛋白，与多种恶性肿瘤有关。在本研究中，使用来自癌症基因组图谱（TCGA）的RNA测序数据评估TPM3表达，并通过受试者工作特征（ROC）曲线检查其与CESC预后的关系。使用细胞计数试剂盒-8（CCK-8）、集落形成和Transwell实验在CESC细胞系中检测TPM3对细胞增殖和迁移的影响，并在小鼠异种移植模型中评估其作用。此外，研究了与TPM3相关的差异表达基因（DEG）以确定其致瘤功能。分析了TPM3、化疗敏感性和免疫浸润之间的关联，以及使用cBioPortal和MethSurv数据库分析了突变、甲基化和预后之间的联系。在CESC样本中观察到TMP3 mRNA和蛋白水平上调，mRNA水平升高与总生存期缩短相关。TPM3在CESC诊断中的曲线下面积（AUC）为0.946，发现其调节肿瘤增殖和转移。总体而言，共鉴定出3099个DEG，发现它们在与CESC进展相关的关键信号通路中富集。TPM3表达还与肿瘤内免疫细胞浸润和免疫检查点活性相关。TPM3表达较高的患者表现出独特的化疗敏感性特征，并且TPM3基因甲基化与CESC患者较差的预后结果相关。总之，TPM3是CESC进展、预后和肿瘤免疫微环境的关键调节因子，表明其作为CESC诊断或预后生物标志物以及免疫治疗靶点的潜力。
