Abstract
BackgroundBecause its metastasis to the lymph nodes are closely related to poor prognosis, miRNAs and mRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of colorectal cancer (CRC). This study aimed to identify novel gene signatures in the lymph node metastasis of CRC.MethodsGSE56350, GSE70574, and GSE95109 datasets were downloaded from the Gene Expression Omnibus (GEO) database, while data from 569 colorectal cancer cases were also downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DE-miRNAs) were calculated using R programming language (Version 3.6.3), while gene ontology and enrichment analysis of target mRNAs were performed using FunRich (http://www.funrich.org). Furthermore, the mRNA–miRNA network was constructed using Cytoscape software (Version 3.8.0). Gene expression levels were verified using the GEO datasets. Similarly, quantitative real-time PCR (qPCR) was used to examine expression profiles from 20 paired non-metastatic and metastatic lymph node tissue samples obtained from patients with CRC.ResultsIn total, five DE-miRNAs were selected, and 34 mRNAs were identified after filtering the results. Moreover, two key miRNAs (hsa-miR-99a, hsa-miR-100) and one gene (heparan sulfate-glucosamine 3-sulfotransferase 2 [HS3ST2]) were identified. The GEO datasets analysis and qPCR results showed that the expression of key miRNA and genes were consistent with that obtained from the bioinformatic analysis. A novel miRNA–mRNA network capable of predicting the prognosis and confirmed experimentally, hsa-miR-99a-HS3ST2-hsa-miR-100, was found after expression analysis in metastasized lymph node tissue from CRC samples.ConclusionIn summary, miRNAs and genes with potential as biomarkers were found and a novel miRNA–mRNA network was established for CRC lymph node metastasis by systematic bioinformatic analysis and experimental validation. This network may be used as a potential biomarker in the development of lymph node metastatic CRC.
Highlights
Because its metastasis to the lymph nodes are closely related to poor prognosis, miRNAs and mRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of colorectal cancer (CRC)
Identification of the miRNAs between non‐metastatic and metastatic lymph node tissues We performed a comprehensive bioinformatics analysis to elucidate the key miRNA–mRNA axis in the metastatic lymph node of CRC
We found that hsa-miR-100 and hsamiR-99a had different expression levels in non-metastasized and metastasized lymph node tissue through quantitative real-time PCR (qPCR) analysis
Summary
Because its metastasis to the lymph nodes are closely related to poor prognosis, miRNAs and mRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of colorectal cancer (CRC). Compared to the early stage of disease, the treatment response and overall survival of patients with advanced CRC is still very poor. Surgical tumor resectioning is still the cornerstone. Wang et al Cancer Cell Int (2021) 21:358 of the treatment of localized, advanced CRC. While lymph node metastasis is not the only form of metastasis in patients with advanced CRC, it is one of the most essential prognostic risk factors [5]. As to promote the prognosis and individualized treatment, it is urgent to determine the key factors influencing lymph node metastasis in CRC
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