胆管内乳头状粘液性肿瘤（IPMN）的病理异质性使胰管腺癌（PDAC）的风险预测更加复杂。胰胆管（PB）、肠道（INT）和胃的小凹（GF）上皮的肿瘤内区域可能伴有低级别或高级别上皮内瘤变。我们利用手术切除的IPMN组织（12例患者的83个区域）的数字空间RNA分析来区分亚型并预测与恶性肿瘤相关的基因。 PB和GF病变的表达模式与INT病变明显不同，表明PB和GF起源于共同的祖先。 PB病变内的转录失调与PDAC相似，而INT和GF病灶则不然。肿瘤坏死因子/nuclear factor κB（TNF-NFκB）和细胞周期（循环S和循环G2-M）程序在PB和INT亚型中相对占据主导地位。 这项研究描绘了高风险IPMN的标志和对恶性进展的见解。

The histopathologic heterogeneity of intraductal papillary mucinous neoplasms (IPMN) complicates the prediction of pancreatic ductal adenocarcinoma (PDAC) risk. Intratumoral regions of pancreaticobiliary (PB), intestinal (INT), and gastric foveolar (GF) epithelium may occur with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). We used digital spatial RNA profiling of dysplastic epithelium (83 regions) from surgically resected IPMN tissues (12 patients) to differentiate subtypes and predict genes associated with malignancy. The expression patterns of PB and GF lesions diverged from INT, suggesting that PB and GF arise from a common lineage. Transcriptional dysregulation within PB lesions mirrored that of PDAC, whereas INT and GF foci did not. Tumor necrosis factor/nuclear factor κB (TNF-NFκB) and cell cycle (cycling S and cycling G2-M) programs occurred with relative prominence in PB and INT subtypes, respectively. Together, this study delineates markers of high-risk IPMN and insights into malignant progression.