Wan Rong, Pan Lujuan, Wang Qi, Shen Guanliang, Guo RuoNan, Qin Yueqiu, Huang Xufeng, Wang Ruo, Fan Xin
Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan 2nd Road, Baise, Guangxi, China.
J Cancer. 2024 May 11;15(11):3580-3595. doi: 10.7150/jca.94360. eCollection 2024.
Copper, an indispensable trace element for the human body, serves not only as a crucial auxiliary factor in redox reactions within the organism but also as a significant constituent of numerous key metabolic enzymes. The COMMD family plays a vital role in regulating copper at both the cellular and systemic levels, particularly in the realm of tumor research, an area notably deficient in gastric cancer investigations. With the advancement of precision medical techniques, individualized and precise screening and treatment have become paramount considerations in the contemporary medical landscape for gastric cancer therapy. In light of this, we meticulously scrutinized existing transcriptomic datasets for gastric cancer, validating the expression levels and prognostic value of COMMD family genes. Simultaneously, employing the ssGSEA algorithm, we devised the COMMDs score. Enrichment analysis, gene mutations, and clinical features were incorporated into the assessment of this score. Furthermore, we contextualized the COMMDs score within the framework of the immune microenvironment, evaluating the relationship between the COMMDs family and immune factors as well as immune cells. The results suggest a correlation between the COMMDs score and various immune-related features. Based on this foundation, multiple machine learning approaches indicated Logistic Regression, with a remarkable ROC of 0.972, as the optimal diagnostic model. To accentuate the translational medical value of the COMMDs family, we selected COMMD10 as a differential gene in gastric cancer for further validation. Functional experiments revealed a decline in the proliferative and migratory capabilities of gastric cancer cells upon silencing COMMD10. Additionally, through pathway intervention, we unveiled the PI3K-AKT pathway as a potential mechanism through which COMMD10 influences gastric cancer activity. In summary, our study affirms the prospective role of the COMMDs family as potential markers for the diagnosis and treatment of gastric cancer in the future.
铜是人体不可或缺的微量元素，它不仅是生物体内氧化还原反应中的关键辅助因子，也是众多关键代谢酶的重要组成部分。COMMD家族在细胞和全身水平的铜调节中发挥着至关重要的作用，尤其是在肿瘤研究领域，而这一领域在胃癌研究方面明显不足。随着精准医疗技术的发展，个体化和精准的筛查与治疗已成为当代胃癌治疗医学领域的首要考虑因素。有鉴于此，我们仔细审查了现有的胃癌转录组数据集，验证了COMMD家族基因的表达水平和预后价值。同时，我们采用单样本基因集富集分析（ssGSEA）算法设计了COMMDs评分。富集分析、基因突变和临床特征被纳入该评分的评估。此外，我们将COMMDs评分置于免疫微环境的框架内，评估COMMD家族与免疫因子以及免疫细胞之间的关系。结果表明COMMDs评分与各种免疫相关特征之间存在相关性。基于此，多种机器学习方法表明逻辑回归作为最佳诊断模型，其受试者工作特征曲线下面积（ROC）高达0.972。为突出COMMD家族的转化医学价值，我们选择COMMD10作为胃癌中的差异基因进行进一步验证。功能实验表明，沉默COMMD10后胃癌细胞的增殖和迁移能力下降。此外，通过通路干预，我们揭示了PI3K-AKT通路是COMMD10影响胃癌活性的潜在机制。总之，我们的研究肯定了COMMD家族在未来作为胃癌诊断和治疗潜在标志物的前瞻性作用。
