Cuproptosis-Related Gene DLAT as a Novel Biomarker Correlated with Prognosis, Chemoresistance, and Immune Infiltration in Pancreatic Adenocarcinoma: A Preliminary Study Based on Bioinformatics Analysis.
Cuproptosis-Related Gene DLAT as a Novel Biomarker Correlated with Prognosis, Chemoresistance, and Immune Infiltration in Pancreatic Adenocarcinoma: A Preliminary Study Based on Bioinformatics Analysis.
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铜中毒相关基因 DLAT 作为与胰腺腺癌预后、化疗耐药和免疫浸润相关的新型生物标志物：基于生物信息学分析的初步研究。
DOI：
10.3390/curroncol30030228
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发表时间：
2023-03-02
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铜中毒是一种新的细胞死亡形式，最近被鉴定为通过铜与三羧酸循环的脂酰化酶的结合来介导。铜中毒相关基因（CRG）可能在胰腺癌（PAAD）的进展中起着至关重要的作用，PAAD经常表现出代谢重编程。在本研究中，进行单因素考克斯回归分析和Kaplan-Meier生存分析以确定预后CRG。下载来自癌症治疗反应门户和癌症药物敏感性基因组学数据库的数据用于药物敏感性分析。DLAT被确定为PAAD中唯一的预后CRG（HR = 2.72; 95% CI，1.10-6.74）。功能富集分析表明，DLAT的基本功能与代谢密切相关，并且在DLAT-高PAAD样品中富集了多种促肿瘤和免疫应答相关途径。通过全面的免疫浸润分析来评估DLAT和相关基因对癌症免疫的影响，这揭示了这些基因作为评估免疫治疗敏感性的生物标志物的价值。此外，DLAT高表达可诱导耐药性，并显着增加PAAD中常用化疗药物（例如吉西他滨、奥沙利铂、5-氟尿嘧啶和伊立替康）的耐药性。本研究初步揭示了DLAT与PAAD进展、化疗耐药及免疫浸润相关的预后价值，为PAAD的治疗提供了有价值的参考。然而，我们的发现需要进一步的体内和体外实验来证实。
A novel form of cell death, cuproptosis, was recently identified to be mediated by the binding of copper to lipoylated enzymes of the tricarboxylic acid cycle. Cuproptosis-related genes (CRGs) may play a crucial role in the progression of pancreatic adenocarcinoma (PAAD), which often exhibits metabolic reprogramming. In the present study, univariate Cox regression analysis and Kaplan–Meier survival analysis were performed to identify prognostic CRGs. Data from the Cancer Therapeutics Response Portal and the Genomics of Drug Sensitivity in Cancer database were downloaded for drug sensitivity analysis. DLAT was identified as the only prognostic CRG in PAAD (HR = 2.72; 95% CI, 1.10–6.74). Functional enrichment analyses indicated that the basic function of DLAT is closely related to metabolism, and multiple tumor-promoting and immune response-related pathways were enriched in DLAT-high PAAD samples. The influence of DLAT and related genes on cancer immunity was evaluated by comprehensive immune infiltration analyses, which revealed the value of these genes as biomarkers for evaluating the sensitivity to immunotherapy. Additionally, high DLAT expression induced drug resistance, and significantly increased resistance to commonly used chemotherapeutics in PAAD, such as gemcitabine, oxaliplatin, 5-fluorouracil, and irinotecan. In conclusion, our study preliminarily revealed the prognostic value of DLAT, which is correlated with PAAD progression, chemoresistance, and immune infiltration, providing a valuable reference for PAAD treatment. However, our findings need to be confirmed by further in vivo and in vitro experiments.
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