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长链非编码 RNA 和信使 RNA 特征与直肠癌新辅助放化疗降期效果相关。

LncRNA and mRNA signatures associated with neoadjuvant chemoradiotherapy downstaging effects in rectal cancer.

机构信息

Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Department of Radiation Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.

出版信息

J Cell Biochem. 2019 Apr;120(4):5207-5217. doi: 10.1002/jcb.27796. Epub 2018 Oct 15.

DOI:10.1002/jcb.27796
PMID:30320451
Abstract

Radiotherapy plays a crucial role in combined treatment modality in local advanced rectal cancer (LARC). While neoadjuvant chemoradiotherapy responses were variable in LARC patients, so, it is important to identify genes that closely associated with short-term and long-term responses to radiotherapy. In this study, we profiled long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression values of LARC patients with different neoadjuvant chemoradiotherapy downstaging depth score based on Agilent Arraystar Human LncRNA V3.0 Array(Agilent, CA). LncRNAs and mRNAs with aberrant expression values between the two groups of LARC patients were identified and lncRNA-miRNA-mRNA regulation network was also obtained through the combination of miRcode and miRTarBase database. Gene interaction network and module analysis of differential expression mRNAs contained in the lncRNA-miRNA-mRNA network identified five hub genes, including KRAS, PDPK1, PPP2R5C, PPP2R1B, and YES1, that should be closely associated with LARC's response to chemoradiotherapy. Besides, Kaplan-Meier analysis based on the Cyber Research Center (CRC) data set from The Cancer Genome Atlas indicated that aberrant expression of the five hub genes is significantly associated with CRC overall survival. In conclusion, we obtained several biomarkers that should be associated with neoadjuvant chemoradiotherapy response in LARC, which should be helpful for individual treatment and prognosis improvement.

摘要

放射治疗在局部晚期直肠癌(LARC)的综合治疗模式中起着至关重要的作用。虽然新辅助放化疗在 LARC 患者中的反应各不相同,但确定与放疗短期和长期反应密切相关的基因非常重要。在这项研究中,我们根据 Agilent Arraystar Human LncRNA V3.0 Array(Agilent,CA)对不同新辅助放化疗降期评分的 LARC 患者的长非编码 RNA(lncRNA)和信使 RNA(mRNA)表达值进行了分析。通过 miRcode 和 miRTarBase 数据库的结合,确定了两组 LARC 患者之间存在异常表达值的 lncRNA 和 mRNA,并获得了 lncRNA-miRNA-mRNA 调控网络。lncRNA-miRNA-mRNA 网络中差异表达 mRNA 的基因相互作用网络和模块分析确定了五个关键基因,包括 KRAS、PDPK1、PPP2R5C、PPP2R1B 和 YES1,这些基因可能与 LARC 对放化疗的反应密切相关。此外,基于癌症基因组图谱中 Cyber Research Center(CRC)数据集的 Kaplan-Meier 分析表明,这五个关键基因的异常表达与 CRC 的总生存率显著相关。总之,我们获得了一些与 LARC 新辅助放化疗反应相关的生物标志物,这可能有助于个体化治疗和改善预后。

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