Abstract

To analyze and construct a survival-related endogenous RNA (ceRNA) network in gastric cancer (GC) with lymph node metastasis, we obtained expression profiles of long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs) in GC from The Cancer Genome Atlas database. The edgeR package was used to screen differentially expressed lncRNAs, mRNAs, and miRNAs between GC patients with lymphatic metastasis and those without lymphatic metastasis. Then, we used univariate Cox regression analysis to identify survival-related differentially expressed RNAs. In addition, we used multivariate Cox regression analysis to screen lncRNAs, miRNAs, and mRNAs for use in the prognostic prediction models. The results showed that 2,247 lncRNAs, 155 miRNAs, and 1,253 mRNAs were differentially expressed between the two patient groups. Using univariate Cox regression analysis, we found that 395 lncRNAs, eight miRNAs, and 180 mRNAs were significantly related to the survival time of GC patients. We next created a survival-related network consisting of 59 lncRNAs, seven miRNAs, and 36 mRNAs. In addition, we identified eight RNAs associated with prognosis by multivariate Cox regression analysis, comprising three lncRNAs (AC094104.2, AC010457.1, and AC091832.1), two miRNAs (miR-653-5p and miR-3923), and three mRNAs (C5orf46, EPHA8, and HPR); these were used to construct the prognostic prediction models, and their risk scores could be used to assess GC patients’ prognosis. In conclusion, this study provides new insights into ceRNA networks in GC and the screening of prognostic biomarkers for GC.

Highlights

  • Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide (Venerito et al, 2018)

  • Many studies have shown that Long non-coding RNAs (lncRNAs) can act as competing endogenous RNA (ceRNA) to regulate the development of gastric cancer (GC); these lncRNAs include MT1JP (Zhang et al, 2018a), TMPO-AS1 (Sun and Han, 2020), and TRPM2-AS (Xiao et al, 2020)

  • As lymphatic metastasis may affect the prognosis of patients, differentially expressed RNAs (DE-RNAs) obtained in this way will be more representative as prognostic biomarkers for GC patients

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Summary

Introduction

Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide (Venerito et al, 2018). MicroRNAs (miRNAs) are a type of noncoding RNA of approximately 22 nucleotides in length They can target the 3' untranslated regions (3' UTRs) of mRNAs, thereby silencing RNA expression at the posttranscriptional level (Kim et al, 2018; Zhang et al, 2018b). The famous competing endogenous RNA (ceRNA) hypothesis proposes that lncRNAs can act as ceRNAs to compete for miRNA response elements, regulating target mRNA expression (Salmena et al, 2011). The function of such a ceRNA network has been verified in many cancers, including Wilms’ tumor (Zheng et al, 2020) and cervical cancer (Chen et al, 2020). The survival-related ceRNA network in GC needs further study

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