Hong Baoan, Zhang Xuezhou, Du Xin, Yang Dazhi, Hu Zhiyuan, Zhang Xiuli, Zhang Ning
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Urology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Diagnostics (Basel). 2023 May 25;13(11):1855. doi: 10.3390/diagnostics13111855.
Studies have shown that the circulating tumor cell (CTC) is a necessary condition for the invasion and distant metastasis of renal cell carcimona (RCC). However, few CTCs-related gene mutations have been developed which could promote the metastasis and implantation of RCC. The objective of this study is to explore the potential driver gene mutations that promote RCC metastasis and implantation based on CTCs culture. Fifteen patients with primary mRCC and three healthy subjects were included, and peripheral blood was obtained. After the preparation of synthetic biological scaffolds, peripheral blood CTCs were cultured. Successful cultured CTCs were applied to construct CTCs-derived xenograft (CDX) models, followed by DNA extraction, whole exome sequencing (WES) and bioinformatics analysis. Synthetic biological scaffolds were constructed based on previously applied techniques, and peripheral blood CTCs culture was successfully performed. We then constructed CDX models and performed WES, and explored the potential driver gene mutations that may promote RCC metastasis and implantation. Bioinformatics analysis showed that KAZN and POU6F2 may be closely related to the prognosis of RCC. We successfully performed the culture of peripheral blood CTCs and, on this basis we initially explored the potential driver mutations for the metastasis and implantation of RCC.
研究表明，循环肿瘤细胞（CTC）是肾细胞癌（RCC）侵袭和远处转移的必要条件。然而，目前很少有与CTC相关的基因突变被发现可促进RCC的转移和植入。本研究的目的是基于CTC培养探索促进RCC转移和植入的潜在驱动基因突变。纳入15例原发性转移性肾细胞癌患者和3名健康受试者，采集外周血。制备合成生物支架后，对外周血CTC进行培养。将成功培养的CTC用于构建源自CTC的异种移植（CDX）模型，随后进行DNA提取、全外显子测序（WES）和生物信息学分析。基于先前应用的技术构建合成生物支架，成功进行了外周血CTC培养。然后我们构建了CDX模型并进行了WES，并探索了可能促进RCC转移和植入的潜在驱动基因突变。生物信息学分析表明，KAZN和POU6F2可能与RCC的预后密切相关。我们成功地进行了外周血CTC的培养，并在此基础上初步探索了RCC转移和植入的潜在驱动突变。
