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基于PCAT7的BRCA临床预后模型探索

Exploration of the clinical prognostic model of BRCA based on PCAT7.

作者信息

Zhang Zhi, Xiang Chaocheng, Chen Tong, Ma Aimin, Wang Xu, Li Jiaying, Chen Yixuan, Huang Chengyu, Li Ting, Wu Danmei, Mo Steven, Li Dequan

机构信息

Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming Hospital, Nanning, China.

Department of Breast Surgery, Guangxi Medical University Affiliated Wuming Hospital, Nanning, China.

出版信息

Front Oncol. 2025 Jul 30;15:1580858. doi: 10.3389/fonc.2025.1580858. eCollection 2025.

DOI:10.3389/fonc.2025.1580858
PMID:40809023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12343279/
Abstract

PURPOSE

Breast cancer (BRCA) is the most common cancer in women. Overexpression of long non-coding RNA Prostate cancer-associated transcript 7 (PCAT7) in BRCA was correlated with an unfavorable prognosis. Consequently, investigating the function and prognostic significance of PCAT7 in BRCA has become imperative.

METHODS

This study used BRCA data from the Cancer Genome Atlas (TCGA) as a training cohort to evaluate the prognostic potential of PCAT7. In addition, luminal A, luminal B, HER2, and basal like triple-negative breast cancer samples were collected clinically to verify the expression of PCAT7. Meanwhile, differentially expressed genes (DEGs) related to PCAT7 were identified. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to identify abnormal regulatory modules of PCAT7 co-expressed genes in BRCA. Furthermore, we used enrichment analysis to evaluate the distribution patterns of genes. We constructed a clinical indicator scoring model based on PCAT7 based prognosis-related genes, followed by correlation analyses to study the relationship between clinical indicators based on PCAT7 expression and immune cell infiltration, immune checkpoint-related genes, and tertiary lymphoid structure marker genes. Pivot analysis based on a hypergeometric approach was used to identify lncRNAs, TFs and RBPs that regulate the set of prognosis-related genes to explore drug targets.

RESULTS

The results showed that PCAT7 was significantly high expression in BRCA, and patients with high expression of PCAT7 had poor prognosis. IHC further confirmed that PCAT7 was significantly overexpressed in BRCA samples of different subtypes, suggesting that PCAT7 has diagnostic potential in BRCA. Meanwhile, a total of 28,892 DEGs and 954 DEmiRNAs were continuously upregulated or downregulated. The most relevant module genes associated with PCAT7 are significantly enriched in immune and cancer-related pathways. PCAT7-based models and model genes were significantly associated with multiple immune checkpoint-related genes and tertiary lymphoid structure marker genes. In addition, PCAT7 is associated with the inhibition of immune cell infiltration.

CONCLUSION

We found that the clinical score of PCAT7 is significantly correlated with the prognosis of BRCA patients, suggesting that PCAT7 is a useful biomarker.

摘要

目的

乳腺癌(BRCA)是女性中最常见的癌症。BRCA中长链非编码RNA前列腺癌相关转录本7(PCAT7)的过表达与不良预后相关。因此,研究PCAT7在BRCA中的功能和预后意义变得势在必行。

方法

本研究使用来自癌症基因组图谱(TCGA)的BRCA数据作为训练队列,以评估PCAT7的预后潜力。此外,临床上收集了腔面A型、腔面B型、HER2型和基底样三阴性乳腺癌样本,以验证PCAT7的表达。同时,鉴定了与PCAT7相关的差异表达基因(DEG)。随后,使用加权基因共表达网络分析(WGCNA)来鉴定BRCA中PCAT7共表达基因的异常调控模块。此外,我们使用富集分析来评估基因的分布模式。我们基于与PCAT7相关的预后基因构建了临床指标评分模型,随后进行相关性分析,以研究基于PCAT7表达的临床指标与免疫细胞浸润、免疫检查点相关基因和三级淋巴结构标记基因之间的关系。基于超几何方法的枢轴分析用于鉴定调控预后相关基因集的长链非编码RNA、转录因子和RNA结合蛋白,以探索药物靶点。

结果

结果显示,PCAT7在BRCA中显著高表达,PCAT7高表达的患者预后较差。免疫组化进一步证实,PCAT7在不同亚型的BRCA样本中显著过表达,表明PCAT7在BRCA中具有诊断潜力。同时,共有28892个DEG和954个差异表达微小RNA(DEmiRNA)持续上调或下调。与PCAT7最相关的模块基因在免疫和癌症相关途径中显著富集。基于PCAT7的模型和模型基因与多个免疫检查点相关基因和三级淋巴结构标记基因显著相关。此外,PCAT7与免疫细胞浸润的抑制有关。

结论

我们发现PCAT7的临床评分与BRCA患者的预后显著相关,表明PCAT7是一种有用的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0990/12343279/eb6335521d98/fonc-15-1580858-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0990/12343279/eb6335521d98/fonc-15-1580858-g008.jpg
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