Jian Ziying, Pan Tao, Li Renjie, Zhang Weiyu, Cheng Tao, Zhang Hanzhe, Song Jialin, Shi Naipeng, Zhang Zhiheng
Department of Hematology, Zhong da Hospital of Southeast University, Nanjing, China.
Department of Radiology, Center of Interventional Radiology and Vascular Surgery, Medical School, Zhongda Hospital, Southeast University, Nanjing, China.
Sci Rep. 2025 Apr 13;15(1):12716. doi: 10.1038/s41598-025-97213-x.
The low immunogenicity of pancreatic cancer inhibits effective antitumor immune responses, primarily due to the immune evasion mediated by low expression of the major histocompatibility complex (MHC). Through comprehensive analysis, our study identifies UPK3B as a gene closely associated with low MHC expression and low immunogenicity in pancreatic cancer. UPK3B has been reported as a marker of primary mesothelial cells, mature epicardium and promotes extracellular matrix signaling. However, the role of UPK3B in pancreatic cancer remain unclear. We found that UPK3B is highly predictive of overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) and is significantly related to clinical features, immune cell infiltration, and response to immune checkpoint inhibitor (ICI) therapy. Gene enrichment analysis revealed significant downregulation of immune regulatory and BCR signaling pathways in the UPK3B high-expression group. Additionally, UPK3B is positively correlated with immunosuppressive cells, suggesting that high UPK3B expression may inhibit antitumor immune responses by promoting low MHC expression. UPK3B is also positively correlated with immune checkpoints, indicating that tumors with high UPK3B expression may not benefit from ICI therapy. Therefore, UPK3B may serve as a novel biomarker and therapeutic target for pancreatic cancer.
胰腺癌的低免疫原性抑制了有效的抗肿瘤免疫反应，这主要是由于主要组织相容性复合体（MHC）低表达介导的免疫逃逸。通过全面分析，我们的研究确定UPK3B是一种与胰腺癌中MHC低表达和低免疫原性密切相关的基因。据报道，UPK3B是原发性间皮细胞、成熟心外膜的标志物，并可促进细胞外基质信号传导。然而，UPK3B在胰腺癌中的作用仍不清楚。我们发现，UPK3B对胰腺导管腺癌（PDAC）患者的总生存期（OS）具有高度预测性，并且与临床特征、免疫细胞浸润以及对免疫检查点抑制剂（ICI）治疗的反应显著相关。基因富集分析显示，UPK3B高表达组中免疫调节和BCR信号通路显著下调。此外，UPK3B与免疫抑制细胞呈正相关，这表明UPK3B高表达可能通过促进MHC低表达来抑制抗肿瘤免疫反应。UPK3B还与免疫检查点呈正相关，这表明UPK3B高表达的肿瘤可能无法从ICI治疗中获益。因此，UPK3B可能成为胰腺癌的一种新型生物标志物和治疗靶点。
