AUTHOR=Wang Ao , Shen Xinglong , Lu Shan , Bi Chao , Cao Yang , Liu Yunfeng , Li Meng , Zhao Yun , Jin Huaizhang , Shen Xiaopeng , Dai Wei , Lei Yang 

TITLE=Comprehensive analyses of single-cell and bulk RNA-seq reveal the biological and prognostic roles of BMP4 in pancreatic adenocarcinoma

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1686938

DOI=10.3389/fmolb.2025.1686938

ISSN=2296-889X

ABSTRACT=Bone Morphogenetic Protein 4 (BMP4) plays a critical role in development, but its function in pancreatic adenocarcinoma (PAAD) is not well understood. We found that BMP4 is minimally expressed in the normal pancreas but markedly upregulated in PAAD, correlating with poor patient survival. Pan-cancer analysis revealed distinct expression and prognostic patterns of BMP4, while pathway analyses indicated that BMP4 predominantly regulates metabolic rather than canonical BMP signaling. Single-cell RNA-seq showed BMP4 enrichment in cancer cells and cancer stem cells, supporting its role in tumor metabolism. Importantly, BMP4 was identified as an independent prognostic factor for PAAD, and a nomogram incorporating BMP4 accurately predicted patient outcomes. Although BMP4 affected certain immune cell infiltrations, its prognostic impact was largely independent of immune modulation. Collectively, these findings highlight BMP4 as a potential biomarker and therapeutic target in PAAD.