Establishment and genetically characterization of patient-derived xenograft models of cervical cancer.
Establishment and genetically characterization of patient-derived xenograft models of cervical cancer.
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DOI：
10.1186/s12920-022-01342-5
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发表时间：
2022-09-08
影响因子：
2.7
通讯作者：
Zhu, Xueqiong
中科院分区：
文献类型：
--
作者：
Zou, Shuangwei;Ye, Miaomiao;Zhang, Jian-an;Ji, Huihui;Chen, Yijie;Zhu, Xueqiong
关键词：
患者来源的异种移植(PDX)模型是为了复制原始癌症的临床情况而建立的，并已越来越多地应用于临床前癌症研究。我们的研究旨在建立宫颈癌PDX模型并对其进行遗传学特征分析。从22个手术切除的宫颈癌组织中获得91个新鲜片段，植入雌性NOD-SCID小鼠皮下。苏木精-伊红(H&E)染色评估所建立的PDX模型是否保留了原始患者宫颈癌组织的组织学特征。此外，维恩图被用来显示在患者原始宫颈癌(F0)和F2-、F3-PDX模型的全基因组测序(WGS)数据中检测到的所有突变的重叠。应用全外显子组测序(WES)和MAFTOOLS程序包检测原发子宫颈癌和已建立的PDX模型中的体细胞突变。我们的研究成功地建立了一组宫颈癌PDX模型，建立宫颈癌PDX模型的潜伏期随传代次数的增加而变化，平均从F1移植的94.71天增长到F3移植的40.65天。此外，宫颈癌PDX模型保留了其原始宫颈癌的组织学特征。WGS显示，在宫颈癌PDX模型中，原始宫颈癌的基因组在移植和传代过程中一直高保真地保存着。此外，WES还证明，宫颈癌PDX模型保持了原始宫颈癌的大部分体细胞突变，其中KMT2D、LRP1B、NAV3、TP53、FAT1、MKI67和PKHD1L1基因是最常见的突变基因。宫颈癌PDX模型保留了其原始宫颈癌的组织学和遗传学特征，有助于更深入地了解宫颈癌的遗传变化，为进一步研究宫颈癌的分子靶向治疗奠定了基础。网上版载有补充材料，可在10.1186/s12920-022-01342-5查阅。
Patient-derived xenograft (PDX) models were established to reproduce the clinical situation of original cancers and have increasingly been applied to preclinical cancer research. Our study was designed to establish and genetically characterize cervical cancer PDX models. A total of 91 fresh fragments obtained from 22 surgically resected cervical cancer tissues were subcutaneously engrafted into female NOD-SCID mice. Hematoxylin and eosin (H&E) staining was performed to assess whether the established PDX models conserved the histological features of original patient cervical cancer tissues. Moreover, a Venn diagram was applied to display the overlap of all mutations detected in whole-genome sequencing (WGS) data from patient original cervical cancer (F0) and F2-, F3-PDX models. The whole exome sequencing (WES) and the “maftools” package were applied to determine the somatic mutations among primary cervical cancers and the established PDX models. Our study successfully developed a panel of cervical cancer PDX models and the latency time of cervical cancer PDX model establishment was variable with a progressive decrease as the passage number increased, with a mean time to initial growth of 94.71 days in F1 engraftment to 40.65 days in F3 engraftment. Moreover, the cervical cancer PDX models preserved the histological features of their original cervical cancer. WGS revealed that the genome of original cervical cancer was preserved with high fidelity in cervical cancer PDX models throughout the xenografting and passaging process. Furthermore, WES demonstrated that the cervical cancer PDX models maintained the majority somatic mutations of original cervical cancer, of which the KMT2D, LRP1B, NAV3, TP53, FAT1, MKI67 and PKHD1L1 genes were identified as the most frequently mutated genes. The cervical cancer PDX models preserved the histologic and genetic characteristics of their original cervical cancer, which helped to gain a deeper insight into the genetic alterations and lay a foundation for further investigation of the molecular targeted therapy of cervical cancer. The online version contains supplementary material available at 10.1186/s12920-022-01342-5.
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PDXliver：肝癌患者异种移植小鼠模型的数据库。
影响因子：
3.8
作者：
He S;Hu B;Li C;Lin P;Tang WG;Sun YF;Feng FY;Guo W;Li J;Xu Y;Yao QL;Zhang X;Qiu SJ;Zhou J;Fan J;Li YX;Li H;Yang XR
通讯作者：
Yang XR
DOI：
10.26355/eurrev_201808_15710
发表时间：
2018-08-01
影响因子：
3.3
作者：
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通讯作者：
Zivadinovic, A.
影响因子：
3.7
作者：
Larmour, Luke, I;Cousins, Fiona L.;Gargett, Caroline E.
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影响因子：
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作者：
Oh DY;Kim S;Choi YL;Cho YJ;Oh E;Choi JJ;Jung K;Song JY;Ahn SE;Kim BG;Bae DS;Park WY;Lee JW;Song S
通讯作者：
Song S
影响因子：
3.9
作者：
Choi, Chel Hun;Choi, Hyun Jin;Kim, Byoung-Gie
通讯作者：
Kim, Byoung-Gie