关键词: metabolism pancreatic cancer profiling transcriptomics tumor infiltrating lymphocytes

来  源:   DOI:10.3389/fonc.2024.1405612   PDF(Pubmed)

Abstract:
UNASSIGNED: Metabolic reprogramming is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC). A pancreatic juice (PJ) metabolic signature has been reported to be prognostic of oncological outcome for PDAC. Integration of PJ profiling with transcriptomic and spatial characterization of the tumor microenvironment would help in identifying PDACs with peculiar vulnerabilities.
UNASSIGNED: We performed a transcriptomic analysis of 26 PDAC samples grouped into 3 metabolic clusters (M_CL) according to their PJ metabolic profile. We analyzed molecular subtypes and transcriptional differences. Validation was performed by multidimensional imaging on tumor slides.
UNASSIGNED: Pancreatic juice metabolic profiling was associated with PDAC transcriptomic molecular subtypes (p=0.004). Tumors identified as M_CL1 exhibited a non-squamous molecular phenotype and demonstrated longer survival. Enrichment analysis revealed the upregulation of immune genes and pathways in M_CL1 samples compared to M_CL2, the group with worse prognosis, a difference confirmed by immunofluorescence on tissue slides. Enrichment analysis of 39 immune signatures by xCell confirmed decreased immune signatures in M_CL2 compared to M_CL1 and allowed a stratification of patients associated with longer survival.
UNASSIGNED: PJ metabolic fingerprints reflect PDAC molecular subtypes and the immune microenvironment, confirming PJ as a promising source of biomarkers for personalized therapy.
摘要:
代谢重编程是胰腺导管腺癌(PDAC)的标志性特征。据报道,胰液(PJ)代谢特征可预测PDAC的肿瘤学结果。将PJ谱与肿瘤微环境的转录组学和空间表征相结合将有助于识别具有特殊脆弱性的PDAC。
我们对26个PDAC样品进行了转录组学分析,根据其PJ代谢谱分为3个代谢簇(M_CL)。我们分析了分子亚型和转录差异。通过对肿瘤载玻片的多维成像进行验证。
胰液代谢谱与PDAC转录组分子亚型相关(p=0.004)。被鉴定为M_CL1的肿瘤表现出非鳞状分子表型并显示出更长的生存期。富集分析显示,与预后较差的M_CL2相比,M_CL1样本中的免疫基因和途径上调,通过组织载玻片上的免疫荧光证实的差异。通过xCell的39个免疫特征的富集分析证实了与M_CL1相比M_CL2中的免疫特征降低,并且允许与更长存活相关的患者的分层。
PJ代谢指纹图谱反映了PDAC分子亚型和免疫微环境,确认PJ是个性化治疗的有希望的生物标志物来源。
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