Shi Jiangmin, Zhao Liang, Wang Kai, Lin Jieqiong, Shen Jianwei
Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital (Lihuili Hospital Affiliated to, Ningbo University), Ningbo, Zhejiang Province, 315040, P.R. China.
Hereditas. 2025 Feb 22;162(1):26. doi: 10.1186/s41065-025-00381-z.
Disulfidptosis, a novel form of metabolism-related regulated cell death, is a promising intervention for cancer therapeutic intervention. Although aberrant expression of long-chain noncoding RNAs (lncRNAs) expression has been associated with pancreatic carcinoma (PC) development, the biological properties and prognostic potential of disulfidptosis-related lncRNAs (DRLs) remain unclear.
We obtained RNA-seq data, clinical data, and genomic mutations of PC from the TCGA database, and then determined DRLs. We developed a risk score model and analyzed the role of risk score in the predictive ability, immune cell infiltration, immunotherapy response, and drug sensitivity.
We finally established a prognostic model including three DRLs (AP005233.2, FAM83A-AS1, and TRAF3IP2-AS1). According to Kaplan-Meier curve analysis, the survival time of patients in the low-risk group was significantly longer than that in the high-risk group. Based on enrichment analysis, significant associations between metabolic processes and differentially expressed genes were assessed in two risk groups. In addition, we observed significant differences in the tumor immune microenvironment landscape. Tumor Immune Dysfunction and Rejection (TIDE) analysis showed no statistically significant likelihood of immune evasion in both risk groups. Patients exhibiting both high risk and high tumor mutation burden (TMB) had the poorest survival times, while those falling into the low risk and low TMB categories showed the best prognosis. Moreover, the risk group identified by the 3-DRLs profile showed significant drug sensitivity.
Our proposed 3-DRLs-based feature could serve as a promising tool for predicting the prognosis, immune landscape, and treatment response of PC patients, thus facilitating optimal clinical decision-making.
二硫化物诱导的细胞焦亡是一种新型的与代谢相关的程序性细胞死亡形式，是癌症治疗干预的一个有前景的靶点。尽管长链非编码RNA（lncRNA）的异常表达与胰腺癌（PC）的发生发展有关，但二硫化物诱导的细胞焦亡相关lncRNA（DRL）的生物学特性和预后潜力仍不清楚。
我们从TCGA数据库中获取了PC的RNA测序数据、临床数据和基因组突变，然后确定了DRL。我们开发了一个风险评分模型，并分析了风险评分在预测能力、免疫细胞浸润、免疫治疗反应和药物敏感性方面的作用。
我们最终建立了一个包含三个DRL（AP005233.2、FAM83A-AS1和TRAF3IP2-AS1）的预后模型。根据Kaplan-Meier曲线分析，低风险组患者的生存时间明显长于高风险组。基于富集分析，在两个风险组中评估了代谢过程与差异表达基因之间的显著关联。此外，我们观察到肿瘤免疫微环境格局存在显著差异。肿瘤免疫功能障碍和排斥（TIDE）分析显示，两个风险组的免疫逃逸可能性均无统计学意义。高风险和高肿瘤突变负荷（TMB）的患者生存时间最差，而低风险和低TMB的患者预后最佳。此外，由3-DRLs特征确定的风险组显示出显著的药物敏感性。
我们提出的基于3-DRLs的特征可以作为预测PC患者预后、免疫格局和治疗反应的有前景的工具，从而促进最佳临床决策。
