Peng Lan, Jiang Meiping, Li Kangming, Yu Shuhui, Zhao Chunfang, Zhang Lan, Li Lan
Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China.
Front Oncol. 2025 Jan 29;15:1422122. doi: 10.3389/fonc.2025.1422122. eCollection 2025.
Studies have shown that more than half of the human genome expression is affected by circadian rhythms, which includes genes involved in cell cycle control, DNA repair and apoptosis that are critical in cancer biology. However, the roles of circadian rhythm-related genes (CRRGs) in cervical cancer (CC) and other common gynecologic cancers remain unclear.
The transcriptome data and clinical information related to CC and other common gynecologic cancers were extracted from the UCSC Xena and Gene Expression Omnibus (GEO) databases. In this study, the differentially expressed CRRGs of CC (target genes) were obtained, and the functional enrichment analysis of these target genes was performed by "clusterProfiler". Then, the biomarkers of CC were screened out to construct the survival risk model (risk score). Moreover, function and tumor micro-environment (TME) analyses in different risk groups were performed for further study of the potential mechanism of CC. Furthermore, the prognostic value and function analyses of biomarkers in three common gynecologic cancers were performed to reveal the potential agreement or heterogeneity regulations.
A total of 19 target genes were associated with pyrimidine metabolism. The survival risk model was constructed with six biomarkers, including APOBEC3B, CDA, HELLS, RHOB, SLC15A3, and UPP1. Among these, APOBEC3B, HELLS, and SLC15A3 were identified as positive factors, while CDA, RHOB, and UPP1 were identified as negative factors in CC. It is notable that multiple immune-related signaling pathways were associated with the clinical risk of CC, and the immunotherapy sensitivity was worse in the high-risk group. In addition, we found that most of biomarkers had the prognostic values in other common gynecologic cancers. It was notable that the mechanisms by which these biomarkers influence gynecologic cancers were associated with extracellular matrix (ECM) receptor interaction, focal adhesion, etc.
This study identified six circadian rhythm-related biomarkers, including APOBEC3B, CDA, HELLS, RHOB, SLC15A3, and UPP1, which were associated with the prognosis of CC. The mechanisms by which these biomarkers influence gynecologic cancers were associated with ECM receptor interaction, focal adhesion, and other functions. These findings might help to deepen the understanding of the agreement or heterogeneity of CRRGs in the pathological processes of common gynecologic cancers.
研究表明，超过一半的人类基因组表达受昼夜节律影响，其中包括参与细胞周期控制、DNA修复和细胞凋亡的基因，这些基因在癌症生物学中至关重要。然而，昼夜节律相关基因（CRRGs）在宫颈癌（CC）和其他常见妇科癌症中的作用仍不清楚。
从UCSC Xena和基因表达综合数据库（GEO）中提取与CC和其他常见妇科癌症相关的转录组数据和临床信息。在本研究中，获得了CC的差异表达CRRGs（靶基因），并通过“clusterProfiler”对这些靶基因进行功能富集分析。然后，筛选出CC的生物标志物以构建生存风险模型（风险评分）。此外，对不同风险组进行功能和肿瘤微环境（TME）分析，以进一步研究CC的潜在机制。此外，对三种常见妇科癌症中的生物标志物进行预后价值和功能分析，以揭示潜在的一致性或异质性调控。
共有19个靶基因与嘧啶代谢相关。用六个生物标志物构建了生存风险模型，包括载脂蛋白B mRNA编辑酶催化多肽样3B（APOBEC3B）、胞苷脱氨酶（CDA）、组蛋白赖氨酸特异性去甲基化酶1（HELLS）、Rho相关B家族小GTP酶（RHOB）、溶质载体家族15成员3（SLC15A3）和泛素蛋白酶体途径1（UPP1）。其中，APOBEC3B、HELLS和SLC15A3被确定为CC的阳性因素，而CDA、RHOB和UPP1被确定为CC的阴性因素。值得注意的是，多个免疫相关信号通路与CC的临床风险相关，高危组的免疫治疗敏感性较差。此外，我们发现大多数生物标志物在其他常见妇科癌症中具有预后价值。值得注意的是，这些生物标志物影响妇科癌症的机制与细胞外基质（ECM）受体相互作用、粘着斑等有关。
本研究确定了六个与昼夜节律相关的生物标志物，包括APOBEC3B、CDA、HELLS、RHOB、SLC15A3和UPP1，它们与CC的预后相关。这些生物标志物影响妇科癌症的机制与ECM受体相互作用、粘着斑和其他功能有关。这些发现可能有助于加深对CRRGs在常见妇科癌症病理过程中的一致性或异质性的理解。
