Zhang Rong, Chai Shengjun, Chen Qihang, Lai Jiaming, Cai Chunmei
Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, Qinghai, People's Republic of China.
Key Laboratory of the Ministry of High Altitude Medicine, Qinghai University Medical College, Xining, Qinghai, People's Republic of China.
Int J Womens Health. 2025 May 26;17:1511-1532. doi: 10.2147/IJWH.S516444. eCollection 2025.
BACKGROUND: Cervical cancer, the fourth leading cause of female cancer mortality globally, faces treatment limitations due to drug resistance and few therapeutic options. This study seeks to identify novel therapeutic targets to address this urgent clinical need. METHODS: Our team identified differentially expressed genes (DEGs) in cervical cancer using gene expression omnibus (GEO) datasets. Subsequently, Mendelian randomization (MR) analysis identified causal gene-cancer relationships, followed by enrichment analysis and The Cancer Genome Atlas (TCGA) validation. Finally, we further validated the functions of the selected target genes in cervical cancer cells and analyzed their Gene Set Enrichment Analysis (GSEA) results, drug sensitivity, and prognostic value. RESULTS: We identified 2,801 upregulated and 1,646 downregulated DEGs. MR analysis identified 21 key cervical cancer-associated genes (14 upregulated, 7 downregulated), with TCGA validation confirming significant differential expression patterns. Among them, few studies have examined these core genes, particularly MERTK and SERPINF1, in cervical cancer. Experiments showed that MERTK and SERPINF1 play a role in cervical cancer. These genes help cancer cells grow, spread, and invade surrounding tissue. Mechanistically, MERTK regulates immune infiltration, whereas SERPINF1 modulates chromosomal activity. Clinically, SERPINF1 enhances overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in individuals with cervical cancer. Moreover, we discovered that several commonly used drugs for cervical cancer treatment, like paclitaxel, showed high efficacy against MERTK and SERPINF1. CONCLUSION: Our study uncovers MERTK and SERPINF1 as critical regulators of cervical cancer progression and survival, offering mechanistic insights into their roles in tumor behavior and the immune microenvironment. These findings provide a foundation for precision therapies, with SERPINF1 restoration and MERTK inhibition as promising strategies. Clinical translation of these targets could address current treatment limitations.
背景：宫颈癌是全球女性癌症死亡的第四大主要原因，由于耐药性和治疗选择有限，面临治疗局限性。本研究旨在确定新的治疗靶点，以满足这一紧迫的临床需求。 方法：我们的团队使用基因表达综合数据库（GEO）数据集确定了宫颈癌中差异表达基因（DEG）。随后，孟德尔随机化（MR）分析确定了因果基因与癌症的关系，接着进行了富集分析和癌症基因组图谱（TCGA）验证。最后，我们进一步验证了所选靶基因在宫颈癌细胞中的功能，并分析了它们的基因集富集分析（GSEA）结果、药物敏感性和预后价值。 结果：我们确定了2801个上调的和1646个下调的DEG。MR分析确定了21个与宫颈癌相关的关键基因（14个上调，7个下调），TCGA验证证实了显著的差异表达模式。其中，很少有研究在宫颈癌中研究这些核心基因，特别是MERTK和SERPINF1。实验表明，MERTK和SERPINF1在宫颈癌中起作用。这些基因帮助癌细胞生长、扩散并侵入周围组织。从机制上讲，MERTK调节免疫浸润，而SERPINF1调节染色体活性。在临床上，SERPINF1可提高宫颈癌患者的总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFI）。此外，我们发现几种常用的宫颈癌治疗药物，如紫杉醇，对MERTK和SERPINF1显示出高疗效。 结论：我们的研究揭示了MERTK和SERPINF1是宫颈癌进展和生存的关键调节因子，为它们在肿瘤行为和免疫微环境中的作用提供了机制性见解。这些发现为精准治疗提供了基础，恢复SERPINF1和抑制MERTK是有前景的策略。这些靶点的临床转化可以解决当前的治疗局限性。
Int J Womens Health. 2025-5-26
Front Cell Dev Biol. 2025-1-24
Zotero 插件
