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

Ao Wang¹Xinglong Shen²Shan Lu³Chao Bi¹Yang Cao³Yunfeng Liu³Meng Li³Yun Zhao²Huaizhang Jin³Xiaopeng Shen³Wei Dai^4*Yang Lei^5*

• ¹College of Physical Education, Anhui Normal University, Wuhu, Anhui, China, WUhu, China
• ²Anhui Normal University, Wuhu, China
• ³College of Life Sciences, Anhui Normal University, Wuhu, Anhui, China, WUhu, China
• ⁴Department of Cadre respiratory, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, Jiangsu, China, Nanjing, China
• ⁵Wuhu Center for Disease Control and Prevention, Wuhu, Anhui, China, WUhu, China

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.