II期结直肠癌患者神经周围侵犯的基因组改变鉴定

Identification of Genomic Alterations of Perineural Invasion in Patients with Stage II Colorectal Cancer.

作者信息

Su Hao, Chang Chen, Hao Jiajie, Xu Xin, Bao Mandula, Luo Shou, Zhao Chuanduo, Liu Qian, Wang Xishan, Zhou Zhixiang, Zhou Haitao

机构信息

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Nov 11;13:11571-11582. doi: 10.2147/OTT.S264616. eCollection 2020.

DOI:10.2147/OTT.S264616

PMID:33204110

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7667198/

Abstract

PURPOSE

The molecular mechanism of perineural invasion (PNI) in stage II colorectal cancer (CRC) remains not to be defined clearly. This study aims to identify the genomic aberrations related to PNI in stage II CRC.

PATIENTS AND METHODS

Using array-based comparative genomic hybridization (array-CGH), primary tumor tissues and paracancerous normal tissues of stage II CRC with PNI and without PNI were analyzed. We identified genomic aberrations by using Genomic Workbench and MD-SeeGH and validated the aberrations of selected genes by real-time polymerase chain reaction (PCR). Gene ontology (GO) and pathway analysis were performed to determine the most likely biological effects of these genes.

RESULTS

The most frequent gains in stage II CRC were at 7q11.21-q11.22, 8p11.21, 8p12-p11.23, 8q11.1-q11.22, 13q12.13-q12.2, and 20q11.21-q11.23 and the most frequent losses were at 17p13.1-p12, 8p23.2, and 118q11.2-q23. Four high-level amplifications at 8p11.23-p11.22, 18q21.1, 19q11-q12, and 20q11.21-q13.32 and homozygous deletions at 20p12.1 were discovered in Stage II CRC. Gains at 7q11.21-q22.1, 16p11.2, 17q23.3-q25.3, 19p13.3-p12, and 20p13-p11.1, and losses at 11q11-q12.1, 11p15.5-p15.1, 18p11.21, and 18q21.1-q23 were more commonly found in patients with PNI by frequency plot comparison together with detailed genomic analysis. It is also observed that gains at 8q11.1-q24.3, 9q13-q34.3, and 13q12.3-q13.1, and losses at 8p23.3-p12, 17p13.3-p11.2, and 21q22.12 occurred more frequently in patients without PNI. Further validation showed that the expression of FLT1, FBXW7, FGFR1, SLC20A2 and SERPINI1 was significantly up-regulated in the NPNI group compared to the PNI group. GO and pathway analysis revealed some genes enriched in specific pathways.

CONCLUSION

These involved genomic changes in the PNI of stage II CRC may be useful to reveal the mechanisms underlying PNI and provide candidate biomarkers.

摘要

目的

II期结直肠癌（CRC）中神经周围浸润（PNI）的分子机制仍未明确界定。本研究旨在鉴定II期CRC中与PNI相关的基因组畸变。

患者与方法

使用基于芯片的比较基因组杂交（array-CGH）技术，对伴有PNI和不伴有PNI的II期CRC的原发性肿瘤组织和癌旁正常组织进行分析。我们使用基因组工作台（Genomic Workbench）和MD-SeeGH软件鉴定基因组畸变，并通过实时聚合酶链反应（PCR）验证所选基因的畸变情况。进行基因本体（GO）和通路分析以确定这些基因最可能的生物学效应。

结果

II期CRC中最常见的扩增区域位于7q11.21-q11.22、8p11.21、8p12-p11.23、8q11.1-q11.22、13q12.13-q12.2和20q11.21-q11.23，最常见的缺失区域位于17p13.1-p12、8p23.2和118q11.2-q23。在II期CRC中发现了位于8p11.23-p11.22、18q21.1、19q11-q12和20q11.21-q13.32的四处高水平扩增以及位于20p12.1的纯合缺失。通过频率图比较及详细的基因组分析发现，7q11.21-q22.1、16p11.2、17q23.3-q25.3、19p13.3-p12和20p13-p11.1区域的扩增以及11q11-q12.1、11p15.5-p15.1、18p11.21和18q21.1-q23区域的缺失在伴有PNI的患者中更为常见。还观察到，8q11.1-q24.3、9q13-q34.3和13q12.3-q13.1区域的扩增以及8p23.3-p12、17p13.3-p11.2和21q22.12区域的缺失在不伴有PNI的患者中更为频繁出现。进一步验证表明，与PNI组相比，非PNI组中FLT1、FBXW7、FGFR1、SLC20A2和SERPINI1的表达显著上调。GO和通路分析揭示了一些在特定通路中富集的基因。