Modeling of cancer-related body-wide effects identifies LTB4 as a diagnostic biomarker for pancreatic cancer.
Modeling of cancer-related body-wide effects identifies LTB4 as a diagnostic biomarker for pancreatic cancer.
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癌症相关全身影响的建模将 LTB4 确定为胰腺癌的诊断生物标志物
DOI：
10.1016/j.ebiom.2022.104050
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发表时间：
2022-06
期刊：
影响因子：
11.1
通讯作者：
Zhang, Zhi-Gang
中科院分区：
文献类型：
--
作者：
Jiang, Shu-Heng;Liu, Dejun;Hu, Li-Peng;Zhang, Shan;Yu, Yanqiu;Sun, Yong-Wei;Ji, Jianguang;Zhang, Zhi-Gang
关键词：
癌症在生物体中引发复杂的适应性反应。关于癌症引起的全身效应的信息有限。在这里，我们评估了胰腺导管腺癌（PDAC）及其前体病变（胰腺上皮内瘤变，PanIN）小鼠模型的多器官变化，以解读PDAC发展过程中发生的变化。在具有PanIN和PDAC的小鼠的脑、结肠、胃、肾、心脏、肝和肺组织中进行RNA测序。差异表达分析和功能类别富集相结合，用于深入了解多器官转录组。通过实时定量聚合酶链反应验证差异表达基因。免疫组织化学染色分析多器官中的神经元和巨噬细胞浸润。采用酶联免疫吸附试验测定小鼠和人血清样本中的白三烯B4（LTB4）水平。确定了PanIN和PDAC阶段不同器官内的转录变化。使用基因本体富集分析，发现增加的中性粒细胞浸润作为中心和突出的受影响特征，其在PanIN阶段发生在肝、肺和胃中。大脑似乎受到很好的保护，免受PanIN或PDAC的后遗症。重要的是，血清LTB 4能够高效区分PDAC与正常对照、慢性胰腺炎和导管内乳头状粘液性肿瘤。我们的研究提供了一个高分辨率的绘图视图的动态多器官转录景观与PDAC及其前驱病变的小鼠。我们的研究结果表明，LTB4可以作为PDAC早期检测的生物标志物。完整的资助者名单可以在致谢部分找到。
Cancer elicits a complex adaptive response in an organism. Limited information is available for the body-wide effects induced by cancer. Here, we evaluated multiorgan changes in mouse models of pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions (pancreatic intraepithelial neoplasia, PanIN) to decipher changes that occur during PDAC development. RNA-sequencing was employed in the brain, colon, stomach, kidney, heart, liver, and lung tissues of mice with PanIN and PDAC. A combination of differential expression analysis and functional-category enrichment was applied for an in-depth understanding of the multiorgan transcriptome. Differentially expressed genes were verified by quantitative real-time polymerase chain reaction. Neutrophil and macrophage infiltration in multiple organs was analyzed by immunohistochemical staining. Leukotriene B4 (LTB4) levels in mouse and human serum samples were determined by enzyme-linked immunosorbent assay. Transcriptional changes within diverse organs during PanIN and PDAC stages were identified. Using Gene Ontology enrichment analysis, increased neutrophil infiltration was discovered as a central and prominent affected feature, which occurred in the liver, lung, and stomach at the PanIN stage. The brain appeared to be well protected from the sequels of PanIN or PDAC. Importantly, serum LTB4 was able to discriminate PDAC from normal controls, chronic pancreatitis, and intraductal papillary mucinous neoplasms with high performance. Our study provides a high-resolution cartographic view of the dynamic multiorgan transcriptomic landscape of mice with PDAC and its precursor lesions. Our findings suggest that LTB4 could serve as a biomarker for the early detection of PDAC. The complete list of funders can be found in the Acknowledgement section.
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DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
影响因子：
28.2
作者：
Incio J;Liu H;Suboj P;Chin SM;Chen IX;Pinter M;Ng MR;Nia HT;Grahovac J;Kao S;Babykutty S;Huang Y;Jung K;Rahbari NN;Han X;Chauhan VP;Martin JD;Kahn J;Huang P;Desphande V;Michaelson J;Michelakos TP;Ferrone CR;Soares R;Boucher Y;Fukumura D;Jain RK
通讯作者：
Jain RK
影响因子：
64.5
作者：
Masri S;Papagiannakopoulos T;Kinouchi K;Liu Y;Cervantes M;Baldi P;Jacks T;Sassone-Corsi P
通讯作者：
Sassone-Corsi P
影响因子：
7.8
作者：
Jala VR;Bodduluri SR;Satpathy SR;Chheda Z;Sharma RK;Haribabu B
通讯作者：
Haribabu B
影响因子：
5.5
作者：
Jiang SH;Zhang XX;Hu LP;Wang X;Li Q;Zhang XL;Li J;Gu JR;Zhang ZG
通讯作者：
Zhang ZG