肺癌仍然是全世界癌症相关死亡的主要原因。肺癌早期阶段的特点是无症状期较长，目前的筛查计划无法有效识别这些症状。这种缺陷意味着失去了提高患者总体生存率的机会。血清生物标志物是癌症筛查和随访最有效的策略之一。使用基于微珠的多重检测，我们筛选了 KrasG12D/ 的血浆和肿瘤； Lkb1f/f (KL) 肺癌小鼠模型，用于寻找可用作生物标志物的细胞因子。我们将金属蛋白酶组织抑制剂 1 (TIMP1) 确定为早期生物标志物，并在肺癌患者血浆中验证了这一发现。我们使用免疫组织化学 (IHC)、之前发表的单细胞 RNA-seq 和批量 RNA-seq 数据来评估肿瘤中 TIMP1 的来源和表达。使用公开的人类蛋白质组和转录组数据库评估 TIMP1 的预后价值。我们发现 TIMP1 是一种肿瘤分泌蛋白，对侵袭性癌症具有高敏感性和特异性，即使在小鼠的早期阶段也是如此。我们发现肿瘤和血清中的 TIMP1 水平与小鼠的肿瘤负荷和较差的生存率相关。我们使用我们机构的临床样本以及公开的人类蛋白质组和转录组数据库验证了这一发现。这些数据支持以下发现：TIMP1 的高肿瘤表达与肺癌患者的不良预后相关。TIMP1 是肺癌检测的合适生物标志物。© 2023 作者。约翰·威利出版的《临床与转化医学》

Lung cancer remains the major cause of cancer-related deaths worldwide. Early stages of lung cancer are characterized by long asymptomatic periods that are ineffectively identified with the current screening programs. This deficiency represents a lost opportunity to improve the overall survival of patients. Serum biomarkers are among the most effective strategies for cancer screening and follow up.Using bead-based multiplexing assays we screened plasma and tumours of the KrasG12D/+; Lkb1f/f (KL) mouse model of lung cancer for cytokines that could be used as biomarkers. We identified tissue inhibitor of metalloproteinase 1 (TIMP1) as an early biomarker and validated this finding in the plasma of lung cancer patients. We used immunohistochemistry (IHC), previously published single-cell RNA-seq and bulk RNA-seq data to assess the source and expression of TIMP1in the tumour. The prognostic value of TIMP1 was assessed using publicly available human proteomic and transcriptomic databases.We found that TIMP1 is a tumour-secreted protein with high sensitivity and specificity for aggressive cancer, even at early stages in mice. We showed that TIMP1 levels in the tumour and serum correlate with tumour burden and worse survival in mice. We validated this finding using clinical samples from our institution and publicly available human proteomic and transcriptomic databases. These data support the finding that high tumour expression of TIMP1 correlates with an unfavorable prognosis in lung cancer patients.TIMP1 is a suitable biomarker for lung cancer detection.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.