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. 2025 Aug 10:625:217788.
doi: 10.1016/j.canlet.2025.217788. Epub 2025 May 15.

Molecular profiling reveals the malignant potential in solid pseudopapillary neoplasms of the pancreas

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Molecular profiling reveals the malignant potential in solid pseudopapillary neoplasms of the pancreas

Jiayi Li et al. Cancer Lett. .

Abstract

Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare tumor primarily affecting middle-aged women, typically characterized by indolent behavior but occasionally demonstrating malignant potential through invasive growth and metastasis. To elucidate the molecular mechanisms driving this heterogeneity, a multi-omics approach was applied to analyze paired metastatic lesions, primary tumors, and normal pancreatic tissues. Methylation profiling via the Illumina Infinium Methylation EPIC BeadChip identified 2425 differentially methylated positions (DMPs) in metastatic versus primary lesions, with 798 DMPs conserved across both lesion types. Tyrosine kinases and cGMP-PKG signaling pathway were the most significantly enriched KEGG pathways involved in the DMPs. Transcriptomic analysis of invasive and non-invasive SPNs using NanoString revealed 99 differentially expressed genes (DEGs). Immunohistochemical validation confirmed elevated protein expression of LY96, IFI16, and GLUD1 in invasive cases. Circulating free DNA (cfDNA) sequencing did not detect genetic mutation in non-metastatic SPN, in contrast, 42.9 % positivity of genetic mutations were detected in metastatic SPNs. Tumor microenvironment analysis by using the GEO database, 850 K methylation sequencing, NanoString transcriptome, highlighted enriched immune-suppressive stromal components in aggressive tumors. These findings establish a molecular signature linking methylation dysregulation, transcriptomic alterations, liquid biopsy, and immune evasion to SPN progression, offering potential biomarkers for risk stratification and therapeutic targeting.

Keywords: Circulating free DNA; Methylation; NanoString; Solid pseudopapillary neoplasm of the pancreas; Tumor microenvironment.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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