Identification and functional characterization of microRNAs reveal a potential role in gastric cancer progression.

Abstract

PURPOSE:

To investigate the potential candidate microRNA (miRNA) biomarkers for the clinical diagnosis, classification, and prognosis of gastric cancer (GC).

METHODS:

We use bioinformatics overlapping subclasses analysis to find the tumor grade and lymphatic metastasis-related GC specific miRNAs from the Cancer Genome Atlas (TCGA) database. Then, we further investigated these GC specific miRNAs distributions in different GC clinical features and their correlations overall survival on the basis of GC patients' information and their related RNA sequencing profile from TCGA. Finally, we randomly selected some of key miRNAs use qRT-PCR to confirm the reliability and validity.

RESULTS:

22 GC specific key miRNAs were identified (Fold-change >2, P < 0.05), 11 of them were discriminatively expressed with tumor size, grade, TNM stage and lymphatic metastasis (P < 0.05). In addition, nine miRNAs (miR-196b-5p, miR-135b-5p, miR-183-5p, miR-182-5p, miR-133a-3p, miR-486-5p, miR-144-5p, miR-129-5p and miR-145-5p) were found to be significantly associated with overall survival (log-rank P < 0.05). Finally, four key miRNAs (miR-183-5p, miR-486-5p, miR-30c-2-3p and miR-133a-3p) were randomly selected to validation and their expression levels in 53 newly diagnosed GC patients by qRT-PCR. Results showed that the fold-changes between TCGA and qRT-PCR were 100 % in agreement. We also found miR-183-5p and miR-486-5p were significantly correlated with tumor TNM stage (P < 0.05), and miR-30c-2-3p and miR-133a-3p were associated with tumor differentiation degree and lymph-node metastasis (P < 0.05). These verified miRNAs clinically relevant, and the bioinformatics analysis results were almost the same.

CONCLUSION:

These key miRNAs may functions as potential candidate biomarkers for the clinical diagnosis, classification and prognosis for GC.

• Authors: C-Y Li, G-Y Liang, W-Z Yao, J Sui, X Shen, Y-Q Zhang, H Peng, W-W Hong, Y-C Ye, Z-Y Zhang, W-H Zhang, L-H Yin, Y-P Pu
• Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (Clin Transl Oncol) Vol. 19 Issue 2 Pg. 162-172 (Feb 2017) ISSN: 1699-3055 [Electronic] Italy
• PMID: 27173517 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Biomarkers, Tumor
• MicroRNAs

Topics

• Adenocarcinoma (genetics, secondary)
• Aged
• Biomarkers, Tumor (genetics)
• Case-Control Studies
• Computational Biology
• Disease Progression
• Female
• Follow-Up Studies
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Lymphatic Metastasis
• Male
• MicroRNAs (genetics)
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Oligonucleotide Array Sequence Analysis
• Prognosis
• Stomach Neoplasms (genetics, pathology)
• Survival Rate