Peng Peiqiang, Zheng Jingying, He Kang, Wang Kai, Wang Longyun, Zheng Xufei, Wu Hao, Yang Zhenning, Zhang Shuang, Zhao Lijing
Department of Medical Rehabilitation, School of Nursing, Jilin University, 965 Xinjiang Street, Chaoyang District, Changchun, 130021, China.
Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, No.4026, Yatai Street, Changchun City, 130000, Jilin Province, China.
Heliyon. 2024 Dec 4;10(24):e40860. doi: 10.1016/j.heliyon.2024.e40860. eCollection 2024 Dec 30.
Cervical squamous cell carcinoma (CESC) is a common cancer in women. Despite advancements in early diagnosis through high-risk human papillomavirus (HPV) screening, challenges remain in predicting and treating the disease. Hence, the identification of novel biomarkers for prognosis and therapeutic targets is crucial. CENPE, a microtubule-end directed motor protein that accumulates during the G2 phase, is recognized for its involvement in promoting cancer growth and progression. However, its specific role in CESC remains unclear. This research investigated the expression of CENPE in CESC utilizing data from The Cancer Genome Atlas (TCGA), which was further validated through gene expression profiles, the Human Protein Atlas (HPA), and clinical data. The study utilized Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis to elucidate the role of CENPE in CESC. Additionally, Protein-protein interaction (PPI) networks and competing endogenous RNA (CeRNA) networks involving CENPE and its differentially expressed genes were established. Furthermore, Kaplan-Meier survival analysis was conducted to evaluate the impact of CENPE on patient prognosis. Our study revealed an upregulation of CENPE expression in cervical cancer tissues, which promotes the progression of CESC through IL-6-mediated PI3K-Akt and MAPK signaling pathways. The significant associations with ACNG3, LY6H, and SLC6A7 suggest that CENPE may play a role in tumor growth and metastasis, potentially involving the nervous system. Moreover, the correlations with ARIH1, KDM1A, KDM5B, and NSD3 indicate that CENPE could be a promising target for drug development. Our analysis of the ROC curve demonstrated a high diagnostic accuracy of CENPE in CESC (AUC: 0.997, CI: 0.990-1.000). Subgroup analysis highlighted substantial effects in patients under 50 years old, those with a height under 160 cm, individuals in peri- and post-menopausal stages, and patients in clinical stages 1 and 4. Additionally, COX regression analysis indicated that older age, lower BMI, and higher CENPE expression are associated with decreased 1-year, 3-year, and 5-year survival rates. In conclusion, CENPE emerges as a crucial factor in the initiation and advancement of cervical cancer, showing potential as a novel target for therapeutic interventions.
宫颈鳞状细胞癌（CESC）是女性常见的癌症。尽管通过高危型人乳头瘤病毒（HPV）筛查在早期诊断方面取得了进展，但在预测和治疗该疾病方面仍存在挑战。因此，识别用于预后和治疗靶点的新型生物标志物至关重要。CENPE是一种在G2期积累的微管末端定向运动蛋白，因其参与促进癌症生长和进展而被认可。然而，其在CESC中的具体作用仍不清楚。本研究利用来自癌症基因组图谱（TCGA）的数据调查了CENPE在CESC中的表达，并通过基因表达谱、人类蛋白质图谱（HPA）和临床数据进一步验证。该研究利用基因本体论（GO）、京都基因与基因组百科全书（KEGG）、基因集富集分析（GSEA）和免疫浸润分析来阐明CENPE在CESC中的作用。此外，还建立了涉及CENPE及其差异表达基因的蛋白质-蛋白质相互作用（PPI）网络和竞争性内源性RNA（CeRNA）网络。此外，进行了Kaplan-Meier生存分析以评估CENPE对患者预后的影响。我们的研究揭示了宫颈癌组织中CENPE表达上调，其通过IL-6介导的PI3K-Akt和MAPK信号通路促进CESC的进展。与ACNG3、LY6H和SLC6A7的显著关联表明CENPE可能在肿瘤生长和转移中起作用，可能涉及神经系统。此外，与ARIH1、KDM1A、KDM5B和NSD3的相关性表明CENPE可能是药物开发的一个有前景的靶点。我们对ROC曲线的分析表明CENPE在CESC中具有较高的诊断准确性（AUC：0.997，CI：0.990 - 1.000）。亚组分析突出了在50岁以下患者、身高低于160厘米的患者、围绝经期和绝经后阶段的个体以及临床分期为1期和4期的患者中的显著影响。此外，COX回归分析表明年龄较大、BMI较低和CENPE表达较高与1年、3年和5年生存率降低相关。总之，CENPE成为宫颈癌发生和进展的关键因素，显示出作为治疗干预新靶点的潜力。
