Division of Endocrinology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Meyer Cancer Center, Weill Cornell Medicine, New York, New York, USA.
Clin Transl Med. 2023 Oct;13(10):e1391. doi: 10.1002/ctm2.1391.
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.
肺癌仍然是全球癌症相关死亡的主要原因。肺癌的早期阶段以无症状期长为特征，而目前的筛查方案无法有效地识别这些无症状期。这一缺陷错失了改善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。
我们使用基于珠的多重分析方法，筛选了 KrasG12D/+; Lkb1f/f（KL）肺癌小鼠模型的血浆和肿瘤中的细胞因子，以寻找可用作生物标志物的细胞因子。我们发现组织金属蛋白酶抑制剂 1（TIMP1）是一种早期生物标志物，并在肺癌患者的血浆中验证了这一发现。我们使用免疫组织化学（IHC）、以前发表的单细胞 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学和转录组学数据库评估 TIMP1 的预后价值。
我们发现 TIMP1 是一种肿瘤分泌的蛋白质，对侵袭性癌症具有高灵敏度和特异性，即使在小鼠的早期阶段也是如此。我们表明，肿瘤和血清中的 TIMP1 水平与肿瘤负担相关，并且与小鼠的生存率降低相关。我们使用来自我们机构的临床样本和公开的人类蛋白质组学和转录组学数据库验证了这一发现。这些数据支持肿瘤中 TIMP1 高表达与肺癌患者预后不良相关的发现。
TIMP1 是一种适合用于肺癌检测的生物标志物。
