de la Fouchardière Christelle, Gamradt Pia, Chabaud Sylvie, Raddaz Maxime, Blanc Ellen, Msika Olivier, Treilleux Isabelle, Bachy Sophie, Cattey-Javouhey Anne, Guibert Pierre, Sarabi Matthieu, Rochefort Pauline, Funk-Debleds Pamela, Coutzac Clélia, Ray-Coquard Isabelle, Peyrat Patrice, Meeus Pierre, Rivoire Michel, Dupré Aurélien, Hennino Ana
Cancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, F-69373 Lyon, France.
Université Lyon 1, F-69000 Lyon, France.
J Pers Med. 2022 Apr 12;12(4):623. doi: 10.3390/jpm12040623.
With an overall survival rate of 2-9% at 5 years, pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related deaths in the industrialized world and is predicted to become the second by 2030. Owing to often late diagnosis and rare actionable molecular alterations, PDAC has not yet benefited from the recent therapeutic advances that immune checkpoint inhibitors (ICI) have provided in other cancer types, except in specific subgroups of patients presenting with tumors with high mutational burden (TMB) or microsatellite instability (MSI). The tumor microenvironment (TME) plays a substantial role in therapeutic resistance by facilitating immune evasion. An extracellular stromal protein, βig-h3/TGFβi, is involved in the pathogenesis of PDAC by hampering T cell activation and promoting stiffness of the TME. The study BIGHPANC included 41 patients with metastatic PDAC, and analyzed βig-h3 levels in serum and tumor samples to assess the βig-h3 prognostic value. βig-h3 serum levels are significantly associated with overall survival (HR 2.05, 95%CI 1.07-3.93; = 0.0301). Our results suggest that βig-h3 serum levels may be considered a prognostic biomarker in patients with metastatic PDAC.
胰腺导管腺癌（PDAC）的5年总生存率为2%-9%，目前是工业化国家癌症相关死亡的第四大主要原因，预计到2030年将成为第二大原因。由于诊断往往较晚且可操作的分子改变罕见，除了在肿瘤突变负荷（TMB）高或微卫星不稳定（MSI）的特定患者亚组中，PDAC尚未从免疫检查点抑制剂（ICI）在其他癌症类型中带来的近期治疗进展中获益。肿瘤微环境（TME）通过促进免疫逃逸在治疗耐药中起重要作用。一种细胞外基质蛋白βig-h3/TGFβi通过阻碍T细胞活化和促进TME的硬度参与PDAC的发病机制。BIGHPANC研究纳入了41例转移性PDAC患者，分析了血清和肿瘤样本中的βig-h3水平以评估βig-h3的预后价值。βig-h3血清水平与总生存率显著相关（HR 2.05，95%CI 1.07-3.93；P = 0.0301）。我们的结果表明，βig-h3血清水平可能被视为转移性PDAC患者的一种预后生物标志物。
