Yin Fangxu, Zhao Wenhao, Ding Chen, Hou Chong, Wang Song, Sun Chao, Zhao Zexia, Zhang Zhanrui, Ren Fan, Liu Yuying, Li Xuanguang
Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.
J Cancer. 2024 Jul 2;15(14):4700-4716. doi: 10.7150/jca.96107. eCollection 2024.
: Long non-coding RNA (lncRNA), a crucial regulator in breast cancer (BC) development, is intricately linked with cellular senescence. However, there is a lack of cellular senescence-related lncRNAs (CSRLs) signature to evaluate the prognosis of BC patients. : Correlation analysis was conducted to identify lncRNAs associated with cellular senescence. Subsequently, a CSRL signature was crafted in the training cohort. The model's accuracy was evaluated through survival analysis and receiver operating characteristic curves. Furthermore, prognostic nomograms amalgamating cellular senescence and clinical characteristics were devised. Tumor microenvironment and checkpoint disparities were compared between low-risk and high-risk groups. The correlation between these signatures and treatment response in BC patients was also investigated. Finally, functional experiments were conducted for validation. : A signature comprising nine CSRLs was devised, which demonstrated adept prognostic capability in BC patients. Functional enrichment analysis revealed that tumor and immune-related pathways were predominantly enriched. Compared to the low-risk group, the high-risk group could benefit more from immunotherapy and certain chemotherapeutic agents. The expression of the 9 CSRLs was validated through in vitro experiments in different subtypes of BC cell lines and tissues. AC098484.1 was specifically verified for its association with senescence-associated secretory phenotypes. : The CSRLs signature emerges as a promising prognostic biomarker for BC, with implications for immunological studies and treatment strategies. AC098484.1 has potential relevance in the treatment of BC cell senescence, and these findings improve the clinical treatment levels for BC patients.
长链非编码RNA(lncRNA)是乳腺癌(BC)发展过程中的关键调节因子,与细胞衰老密切相关。然而,目前缺乏用于评估BC患者预后的细胞衰老相关lncRNAs(CSRLs)特征。
进行相关性分析以鉴定与细胞衰老相关的lncRNAs。随后,在训练队列中构建了CSRLs特征。通过生存分析和受试者工作特征曲线评估模型的准确性。此外,还设计了结合细胞衰老和临床特征的预后列线图。比较了低风险组和高风险组之间的肿瘤微环境和检查点差异。还研究了这些特征与BC患者治疗反应之间的相关性。最后,进行功能实验以进行验证。
设计了一个包含9个CSRLs的特征,该特征在BC患者中显示出良好的预后能力。功能富集分析表明,肿瘤和免疫相关途径占主导地位。与低风险组相比,高风险组可能从免疫疗法和某些化疗药物中获益更多。通过在不同亚型的BC细胞系和组织中进行体外实验验证了9个CSRLs的表达。特别验证了AC098484.1与衰老相关分泌表型的关联。
CSRLs特征是一种有前景的BC预后生物标志物,对免疫学研究和治疗策略具有重要意义。AC098484.1在BC细胞衰老治疗中具有潜在相关性,这些发现提高了BC患者的临床治疗水平。