College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Mol Cancer. 2024 Nov 18;23(1):258. doi: 10.1186/s12943-024-02169-7.
Millions of new cases of cancer are diagnosed worldwide each year, making it a serious public health concern. Developments in customized therapy and early detection have significantly enhanced treatment for and results from cancer. Therefore, it is important to investigate new molecular biomarkers. In this study, we created an efficient transient receptor potential melastatin (TRPM) family members-related TRPM-Score for 17 solid tumors. CCNE1, produced from TRPM-Score, was found to be an exceptional biomarker through several sophisticated machine learning and deep learning computational techniques. TRPM-Score and CCNE1 immunotherapeutic prediction, immunological characteristics, and predictive value were thoroughly assessed. In most cancer types, CCNE1 was a substantially dangerous marker. Additional in vitro tests validated CCNE1's immunomodulatory properties, demonstrating that silencing impeded macrophage movement and decreased PD-L1 expression. Additionally, CCNE1 may accurately predict responses to cancer immunotherapy. These findings indicate that the TRPM family-particularly CCNE1, which is associated with TRPM-is a significant player in the pan-cancer domain and can be utilized as a therapeutic target and prognostic biomarkers, especially in immuno-oncology. The thorough characterization of the TRPM family and the discovery of CCNE1 as a crucial downstream effector mark important developments in our comprehension of pan-cancer biology.
每年全球都有数百万人被诊断出患有癌症,这是一个严重的公共卫生问题。定制疗法和早期检测方面的进展显著提高了癌症的治疗效果和结果。因此,研究新的分子生物标志物非常重要。在这项研究中,我们为 17 种实体肿瘤创建了一个有效的瞬时受体电位 melastatin (TRPM) 家族成员相关的 TRPM 评分。通过几种复杂的机器学习和深度学习计算技术,发现源自 TRPM 评分的 CCNE1 是一种出色的生物标志物。我们全面评估了 TRPM 评分和 CCNE1 的免疫治疗预测、免疫特征和预测价值。在大多数癌症类型中,CCNE1 是一个非常危险的标志物。额外的体外测试验证了 CCNE1 的免疫调节特性,表明沉默会阻碍巨噬细胞的运动并降低 PD-L1 的表达。此外,CCNE1 可能可以准确预测癌症免疫治疗的反应。这些发现表明,TRPM 家族,特别是与 TRPM 相关的 CCNE1,是泛癌领域的重要参与者,可作为治疗靶点和预后生物标志物,特别是在免疫肿瘤学中。TRPM 家族的全面表征以及 CCNE1 作为关键下游效应标志物的发现,是我们对泛癌生物学理解的重要进展。