LIMD2 is a Prognostic and Predictive Marker in Patients With Esophageal Cancer Based on a ceRNA Network Analysis.

Yuanmei Chen,Lin Chen,Haiyan Peng,Yuanji Xu,Tianya Xiao,Junqiang Chen,Guibin Weng,Yangfan Zhang,Changkun Li,Kunshou Zhu,Zhengrong Huang,Xinyi Huang

doi:10.3389/fgene.2021.774432

Yuanmei Chen, Lin Chen + Show 10 more

Open Access

https://doi.org/10.3389/fgene.2021.774432

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Abstract

Globally, esophageal cancer (ECA) is the seventh most common cancer and sixth most common cause of cancer-associated mortality. However, there are no reliable prognostic and predictive molecular markers for ECA; in addition, the pathogenesis of ECA is not fully elucidated. The expressions of circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) of ECA and control groups were obtained from the RNA-sequencing (RNA-seq) data of our hospital, the Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) datasets. Analyses of differentially expressed genes, the circRNA–miRNA–mRNA–competing endogenous RNA (ceRNA) network, and functional/pathway enrichment were conducted. The key targets in the ceRNA network that showed significant results in survival Cox regression analyses were selected. Furthermore, analyses of immune infiltration and autophagy genes related to the key targets were performed. Seven circRNAs, 22 miRNAs, and 34 mRNAs were identified as vital genes in ECA; the nuclear factor-κ-gene binding (NF-κB) and phosphatidylinositol-3 kinase/protein kinase B (PI3K-Akt) signaling were identified as the most enriched pathways. In addition, the LIM domain containing 2 (LIMD2) was an independent predictor of prognosis in ECA patients and closely associated with immunity and autophagy. Moreover, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed significant upregulation of LIMD2 expression in ECA tissues. ECA may be closely correlated with NF-κB and PI3K/Akt signaling. In addition, LIMD2 could be a potential prognostic and predictive marker of ECA.

Highlights

Esophageal cancer (ECA), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is the seventh most common malignant tumor in the world and the sixth most common primary cause of tumor-associated death, especially in Asia (Bray et al, 2018)
The results showed that most principal components could separate or tended to separate esophageal cancer (ECA) samples from normal esophageal tissues
GSE131969 (Figure 1B), 493 DEcircRNAs were identified in RNA-seq data (Figure 1E), 1576 differentially expressed mRNAs (DEmRNAs) were identified in RNA-seq data (Figure 2B), 2450 DEmRNAs were identified in The Cancer Genome Atlas (TCGA) (Figure 2E), and 86 DEmRNAs were identified in TCGA (Figure 3B)

Summary

Introduction

Esophageal cancer (ECA), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is the seventh most common malignant tumor in the world and the sixth most common primary cause of tumor-associated death, especially in Asia (Bray et al, 2018). In-depth exploration of potential prognostic and predictive markers, therapeutic targets, and mechanisms of ECA is a key imperative to improve the treatment outcomes and prognosis of ECA patients. Recent studies have found that the mRNAs targeted by miRNAs in the circRNA–miRNA–mRNA–competing endogenous RNA (ceRNA) regulatory network could serve as a key therapeutic target in cancer. CircRNAs in the ceRNA network may indirectly regulate those target mRNAs by serving as miRNA “sponges” (Zhang et al, 2017; Wu et al, 2019). Low expression of large tumor suppressor kinase 1 (LATS1) was found to be related to the tumor stage and poor prognosis of gastric cancer patients; in addition, circLARP4 was found to inhibit the malignant biological behavior of gastric cancer as a tumor suppressor via the modulation of the circLARP4/miR-424-5p/LATS1 axis (Yang et al, 2018)

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