Yang Shasha, Zeng Jingjing, Wang Yong, Tan Yudi, Yu Li, Wei Jinkong, Wei Yuying, Jin Yuxuan, Chen Junying
Department of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical University, Nanning City, 530000, Guangxi Zhuang Autonomous Region, China.
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning City, 530000, Guangxi Zhuang Autonomous Region, China.
Sci Rep. 2025 Aug 12;15(1):29538. doi: 10.1038/s41598-025-14823-1.
The aberrant expression of RNA binding proteins (RBPs) is linked to various diseases, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the single-cell landscape of RBPs in CESC remains unclear. We analyzed single-cell data from 2 HPV + and 2 HPV- CESC samples to assess cell subtype composition and differential gene expression. Meanwhile, based on 2,141 reported RBPs, the expression patterns of different cell type-specific RBPs were further investigated. SUVA software was used to perform differential alternative splicing analysis on the TCGA CESC data. Finally, we did a lot of follow-up work and immunohistochemical studies to understand the true expression of RBP and its correlation with CESC prognosis. We observed a significant increase in the proportion of epithelial cells in the HPV + sample. The expression of RBP exhibited heterogeneity between HPV + and HPV- samples, with epithelial cells demonstrating the most diverse composition of RBP-expressing cell clusters. Results indicated that RNA splicing events were strongly associated with CESC progression. Covariation analysis identified 4 RBPs (CSTB, TIPARP, NDRG1, and NDRG2) correlated with 25 RNA alternative splicing events. Immunohistochemical experiments revealed that TIPARP expression was down-regulated in HPV + cervical cancer(p = 0.033). And the prognostic model that includes all RBPs, stage, and treatments may has have certain practical guiding significance for patients with CESC. Our study indicates that RBPs display specific expression patterns across HPV + and HPV- CESC. The regulatory checkpoints of these RBPs may serve as potential markers and therapeutic targets for the detection of HPV + CESC.
RNA结合蛋白（RBPs）的异常表达与包括宫颈鳞状细胞癌和宫颈管腺癌（CESC）在内的多种疾病相关。然而，CESC中RBPs的单细胞图谱仍不清楚。我们分析了来自2个HPV阳性和2个HPV阴性CESC样本的单细胞数据，以评估细胞亚型组成和差异基因表达。同时，基于2141个已报道的RBPs，进一步研究了不同细胞类型特异性RBPs的表达模式。使用SUVA软件对TCGA CESC数据进行差异可变剪接分析。最后，我们做了大量的后续工作和免疫组化研究，以了解RBP的真实表达及其与CESC预后的相关性。我们观察到HPV阳性样本中上皮细胞比例显著增加。RBP的表达在HPV阳性和HPV阴性样本之间表现出异质性，上皮细胞显示出表达RBP的细胞簇组成最多样化。结果表明，RNA剪接事件与CESC进展密切相关。共变分析确定了4个与25个RNA可变剪接事件相关的RBPs（CSTB、TIPARP、NDRG1和NDRG2）。免疫组化实验显示，TIPARP在HPV阳性宫颈癌中的表达下调（p = 0.033）。并且包括所有RBPs、分期和治疗方法的预后模型可能对CESC患者具有一定的实际指导意义。我们的研究表明，RBPs在HPV阳性和HPV阴性CESC中表现出特定的表达模式。这些RBPs的调控检查点可能作为检测HPV阳性CESC的潜在标志物和治疗靶点。
