英国弗朗西斯·克里克研究所Charles Swanton课题组开发出血浆信号促进肺癌的分子预防。2026年6月4日出版的《细胞》发表了这项成果。
通过机器学习，该课题组人员确定了一个14蛋白的血浆特征，可以在诊断前5年以上预测肺癌。该特征在8个队列中得到验证，在当前吸烟者和暴露于颗粒物（PM）并与肺髓细胞和肺泡细胞有关的个体中升高。在表皮生长因子受体（EGFR）驱动的肺腺癌中，不同的上皮谱系聚集在角化蛋白8+/claudin4+肺泡过渡状态（KAC）上，其转录程序与特征出现相关。标记的成分由PM、致癌EGFR或IL-1β诱导，而IL-1β抑制PM驱动的KAC扩增和早期肿瘤发生。在CANTOS中，该特征确定了似乎从抗IL-1β治疗中获益更多的个体，降低了NNT阈值，并指定肿瘤促进循环信号用于预防。
研究人员表示，预测肺癌风险将加强预防试验。尽管Canakinumab抗炎血栓结局研究（CANTOS）试验表明，白细胞介素(IL)-1β抑制可降低肺癌发病率，但预防肺癌所需的高剂量治疗（NNT）限制了其在未选择人群中的应用。
附：英文原文
Title: Plasma signals of lung tumor promotion for molecular cancer prevention
Author: Tej Pandya, Maria Zagorulya, Michelle M. Leung, Marcellus Augustine, Lydia Y. Liu, Aino-Maija Lepp, Ulysse Baruchel, Sin Wi Ng, Tamara Klockner, Miriam Mugabo, Anthony J. Griffen, Oleg Blyuss, Chrysante S. Iliakis, Amalie Grenov, Kerstin Haase, David C. Muller, Ka Hung Chan, Jincheng Wu, Vernon A. Burk, Neil Wright, Alix Le Marois, Ekaterina Pazukhina, Sophia Ward, Hubert Slawinski, Marc Pelletier, Cian Murphy, Matthew D. Park, Thomas Snoeks, Alejandro Suarez-Bonnet, Simon L. Priestnall, Alexandros Hardas, Charlotte Grieco, Ami Archer, Alpkaan Celik, Alejandro Jimenez-Sanchez, Rachel Scott, Hana Zahed, Léa Montégut, Rafael Meza, Clinton H. Durney, Stephen Lam, Takahiro Karasaki, Roel C.H. Vermeulen, Huilei Xu, Pablo Serrano-Fernandez, Tatjana Crnogorac-Jurcevic, Usha Menon, Sophia Apostolidou, Alexey Zaikin, Richard Gunu, Harry J. Whitwell, Zhe Huang, Zonglun Li, Xin Hu, Bo Zhu, Liming Li, María-Dolores Chirlaque, Marcela Guevara
Issue&Volume: 2026-06-04
Abstract: Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8+/claudin4+ alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR, or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.
DOI: 10.1016/j.cell.2026.05.005
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00522-2