TIMP1 is an early biomarker for detection and prognosis of lung cancer.
TIMP1 is an early biomarker for detection and prognosis of lung cancer.
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DOI：
10.1002/ctm2.1391
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发表时间：
2023-10
影响因子：
10.6
通讯作者：
Goncalves, Marcus D.
中科院分区：
文献类型：
--
作者：
Dantas, Ezequiel;Murthy, Anirudh;Ahmed, Tanvir;Ahmed, Mujmmail;Ramsamooj, Shakti;Hurd, Maurice A.;Lam, Tiffany;Malbari, Murtaza;Agrusa, Christopher;Elemento, Olivier;Zhang, Chen;Pappin, Darryl J.;McGraw, Timothy E.;Stiles, Brendon M.;Altorki, Nasser K.;Goncalves, Marcus D.
肺癌仍然是全球癌症相关死亡的主要原因。早期肺癌的特征是长时间无症状，目前的筛查计划无法有效识别。这种缺陷意味着失去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的最有效策略之一。使用基于微珠的多重分析，我们筛选了KrasG 12 D/+; Lkb 1f/f（KL）肺癌小鼠模型的血浆和肿瘤中可用作生物标志物的细胞因子。我们鉴定了金属蛋白酶组织抑制剂1（TIMP 1）作为早期生物标志物，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），先前发表的单细胞RNA测序和批量RNA测序数据来评估肿瘤中TIMP 1的来源和表达。TIMP 1的预后价值使用公开的人类蛋白质组学和转录组学数据库进行评估。我们发现TIMP 1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。我们发现肿瘤和血清中的TIMP 1水平与小鼠的肿瘤负荷和较差的存活率相关。我们使用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TIMP 1的高肿瘤表达与肺癌患者的不良预后相关的发现。TIMP 1是肺癌检测的合适生物标志物。肺癌仍然是全球癌症相关死亡的主要原因。我们发现金属蛋白酶组织抑制剂1（TIMP 1）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，TIMP 1在肿瘤和血清中的水平与小鼠的肿瘤负荷和较差的存活率相关。我们使用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TIMP 1的高肿瘤表达与肺癌患者的不良预后相关的发现。
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. Lung cancer remains the major cause of cancer‐related deaths worldwide. We found that the tissue inhibitor of metalloproteinase 1 (TIMP1) is a tumour‐secreted protein with high sensitivity and specificity for aggressive cancer, even at early stages in mice. We show 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.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
64.5
作者：
Gillette, Michael A.;Satpathy, Shankha;Carr, Steven A.
通讯作者：
Carr, Steven A.
影响因子：
82.9
作者：
Laughney, Ashley M.;Hu, Jing;Massague, Joan
通讯作者：
Massague, Joan
影响因子：
8.8
作者：
Altorki, Nasser K.;Borczuk, Alain C.;Harrison, Sebron;Groner, Lauren K.;Bhinder, Bhavneet;Mittal, Vivek;Elemento, Olivier;McGraw, Timothy E.
通讯作者：
McGraw, Timothy E.
影响因子：
64.8
作者：
Ji, Hongbin;Ramsey, Matthew R.;Wong, Kwok-Kin
通讯作者：
Wong, Kwok-Kin