Construction of a three-component regulatory network of transcribed ultraconserved regions for the identification of prognostic biomarkers in gastric cancer

Research output: Contribution to journalResearch articleContributedpeer-review


  • Anis Khalafiyan - , Isfahan University of Medical Sciences (Author)
  • Modjtaba Emadi-Baygi - , Shahrekord University (Author)
  • Markus Wolfien - , Centre for Medical Informatics, University of Rostock (Author)
  • Ali Salehzadeh-Yazdi - , Jacobs University Bremen (Author)
  • Parvaneh Nikpour - , Isfahan University of Medical Sciences (Author)


Altered expression and functional roles of the transcribed ultraconserved regions (T-UCRs), as genomic sequences with 100% conservation between the genomes of human, mouse, and rat, in the pathophysiology of neoplasms has already been investigated. Nevertheless, the relevance of the functions for T-UCRs in gastric cancer (GC) is still the subject of inquiry. In the current study, we first used a genome-wide profiling approach to analyze the expression of T-UCRs in GC patients. Then, we constructed a three-component regulatory network and investigated potential diagnostic and prognostic values of the T-UCRs. The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) dataset was used as a resource for the RNA-sequencing data. FeatureCounts was utilized to quantify the number of reads mapped to each T-UCR. Differential expression analysis was then conducted using DESeq2. In the following, interactions between T-UCRs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were combined into a three-component network. Enrichment analyses were performed and a protein-protein interaction (PPI) network was constructed. The R Survival package was utilized to identify survival-related significantly differentially expressed T-UCRs (DET-UCRs). Using an in-house cohort of GC tissues, expression of two DET-UCRs was furthermore experimentally verified. Our results showed that several T-UCRs were dysregulated in TCGA-STAD tumoral samples compared to nontumoral counterparts. The three-component network was constructed which composed of DET-UCRs, miRNAs, and mRNAs nodes. Functional enrichment and PPI network analyses revealed important enriched signaling pathways and gene ontologies such as "pathway in cancer" and regulation of cell proliferation and apoptosis. Five T-UCRs were significantly correlated with the overall survival of GC patients. While no expression of uc.232 was observed in our in-house cohort of GC tissues, uc.343 showed an increased expression, although not statistically significant, in gastric tumoral tissues. The constructed three-component regulatory network of T-UCRs in GC presents a comprehensive understanding of the underlying gene expression regulation processes involved in tumor development and can serve as a basis to investigate potential prognostic biomarkers and therapeutic targets.


Original languageEnglish
Pages (from-to)396-408
Number of pages13
JournalJournal of cellular biochemistry
Issue number3
Publication statusPublished - Mar 2023

External IDs

Scopus 85147527095
ORCID /0000-0002-1887-4772/work/149439286


Sustainable Development Goals


  • Humans, Rats, Mice, Animals, Stomach Neoplasms/genetics, Prognosis, Conserved Sequence/genetics, Gene Expression Regulation, Neoplastic, MicroRNAs/genetics, Adenocarcinoma/genetics, Biomarkers, RNA, Long Noncoding, Gene Regulatory Networks, Biomarkers, Tumor/genetics