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筛选与食管鳞癌肿瘤分级相关的 mRNAs 和 lncRNAs。

Screening of tumor grade-related mRNAs and lncRNAs for Esophagus Squamous Cell Carcinoma.

机构信息

Department of Radiotherapy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Department of Oncology, Dongying People's Hospital, Dongying, China.

出版信息

J Clin Lab Anal. 2021 Jun;35(6):e23797. doi: 10.1002/jcla.23797. Epub 2021 May 7.

DOI:10.1002/jcla.23797
PMID:33960436
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8183932/
Abstract

BACKGROUND

The goal of our study was to screen tumor grade-related lncRNAs and mRNAs to reveal the underlying molecular mechanism of esophagus squamous cell carcinoma (ESCC).

METHODS

The lncRNA and mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA). Tumor grade correlation analysis of lncRNAs and mRNAs was executed, followed by the functional enrichment analysis of all tumor grade-related mRNAs. The differentially expression mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were obtained. PPI network and DEmRNA-DElncRNA interaction analysis were constructed. The functional annotation of the DEmRNAs co-expressed with DElncRNAs was performed. The expression levels of the candidate genes were validated using qRT-PCR.

RESULTS

A total of 1864 tumor grade-related mRNAs (846 positively related and 1018 negatively related) and 552 tumor grade-related lncRNAs (331 positively related and 221 negatively related) were obtained. The top 10 significantly grade-related mRNAs and lncRNAs included CA12, FABP4, DECR1, BAIAP2, IL1RAPL2, PPARD, LAD1, TSPAN10, LDOC1, ZNF853, RP11-25G10.2, RP11-557H15.3, RP11-521D12.5, CHKB-AS1, RP11-219B4.3, CH17-335B8.4, RP11-99 J16-A.2, CTB-111H14.1, ADNP-AS1, and JHDM1D-AS1. SFN, IL1RAPL2, and RP11-25G10.2 were overlapped from grade 1, grade 2, and grade 3. PPI network showed that top 10 proteins with higher degrees, including GNAI1, RAP2B, GNAZ, SHH, ADCY1, PRKAR2B, SH3GL1, GNA15, and ARRB1. A DElncRNAs-nearby DEmRNAs network was constructed to obtain hub lncRNAs including ADAMTS9-AS2, RP11-210 M15.2, RP11-13 K12.1, ZBED3-AS1, and RP11-25G10.2. Except for RP11-25G10.2, ADAMTS9-AS1, ZBED3-AS1, SFN, ATP1A2, and GNA15 were consistent with our TCGA analysis.

CONCLUSIONS

Alterations of DEmRNAs and DElncRNAs may provide key insights into the molecular mechanisms of ESCC.

摘要

背景

本研究旨在筛选与肿瘤分级相关的长链非编码 RNA（lncRNA）和信使 RNA（mRNA），以揭示食管鳞状细胞癌（ESCC）的潜在分子机制。

方法

从癌症基因组图谱（TCGA）中获取 lncRNA 和 mRNA 测序数据。对 lncRNA 和 mRNA 进行肿瘤分级相关性分析，然后对所有与肿瘤分级相关的 mRNA 进行功能富集分析。获得差异表达的 mRNA（DEmRNAs）和差异表达的 lncRNA（DElncRNAs）。构建 PPI 网络和 DEmRNA-DElncRNA 相互作用分析。对与 DElncRNAs 共表达的 DEmRNAs 进行功能注释。使用 qRT-PCR 验证候选基因的表达水平。

结果

共获得 1864 个与肿瘤分级相关的 mRNAs（846 个正相关，1018 个负相关）和 552 个与肿瘤分级相关的 lncRNAs（331 个正相关，221 个负相关）。前 10 个与分级显著相关的 mRNAs 和 lncRNAs 包括 CA12、FABP4、DECR1、BAIAP2、IL1RAPL2、PPARD、LAD1、TSPAN10、LDOC1、ZNF853。RP11-25G10.2、RP11-557H15.3、RP11-521D12.5、CHKB-AS1、RP11-219B4.3、CH17-335B8.4、RP11-99J16-A.2、CTB-111H14.1、ADNP-AS1 和 JHDM1D-AS1。SFN、IL1RAPL2 和 RP11-25G10.2 从 1 级、2 级和 3 级重叠。PPI 网络显示，前 10 个具有较高度数的蛋白质，包括 GNAI1、RAP2B、GNAZ、SHH、ADCY1、PRKAR2B、SH3GL1、GNA15 和 ARRB1。构建了一个 DElncRNAs-邻近 DEmRNAs 网络，以获得包括 ADAMTS9-AS2、RP11-210M15.2、RP11-13K12.1、ZBED3-AS1 和 RP11-25G10.2 在内的核心 lncRNAs。除了 RP11-25G10.2 外，ADAMTS9-AS2、ZBED3-AS1、SFN、ATP1A2 和 GNA15 与我们的 TCGA 分析一致。

结论

DEmRNAs 和 DElncRNAs 的改变可能为 ESCC 的分子机制提供关键见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74cd/8183932/260e660405e0/JCLA-35-e23797-g009.jpg
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