Bioinformatics analysis and experimental validation of TTK as a biomarker for prognosis in non-small cell lung cancer.

Abstract

BACKGROUND:

Despite the prominent development of medical technology in recent years, the prognosis of non-small cell lung cancer (NSCLC) is still not optimistic. It is crucial to identify more reliable diagnostic biomarkers for the early diagnosis and personalized therapy of NSCLC and clarify the molecular mechanisms underlying NSCLC progression.

METHODS:

In the present study, bioinformatics analysis was performed on three datasets obtained from the Gene Expression Omnibus to identify the NSCLC-associated differentially expressed genes (DEGs). Immunohistochemistry-based tissue microarray of human NSCLC was used to experimental validating the potential targets obtained from bioinformatics analysis.

RESULTS:

By using protein-protein interaction (PPI) network analysis, Kaplan-Meier plotter, and Gene Expression Profiling Interactive Analysis, we selected 40 core DEGs for further study. Then, a re-analysis of 40 selected genes via Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that nine key genes involved in the cell cycle and p53 signaling pathway participated in the development of NSCLC. Then, we checked the protein level of nine key genes by semi-quantitative of IHC and checked the distribution at a single-cell level. Finally, we validated dual-specificity protein kinase TTK as a biomarker for prognosis in a tissue microarray. High TTK expression associated with a higher histological stage, advanced TNM stage, high frequency of positive lymph nodes, and worse 5-year overall survival.

CONCLUSIONS:

We found nine key genes were enriched in the cell cycle and p53 signaling pathway. TTK could be considered as a potential therapeutic target and for the prognosis biomarker of NSCLC. These findings will provide new insights for the development of individualized therapeutic targets for NSCLC.

• Authors: Jiajia Chen, Rong Wu, Ying Xuan, Min Jiang, Yuecan Zeng
• Journal: Bioscience reports (Biosci Rep) Vol. 40 Issue 10 (10 30 2020) ISSN: 1573-4935 [Electronic] England
• PMID: 32969465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s).

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• Protein Kinase Inhibitors
• Protein-Tyrosine Kinases
• Protein Serine-Threonine Kinases
• TTK protein, human

Topics

• Aged
• Biomarkers, Tumor (analysis, antagonists & inhibitors, metabolism)
• Carcinoma, Non-Small-Cell Lung (diagnosis, drug therapy, genetics, mortality)
• Cell Cycle Proteins (analysis, antagonists & inhibitors, metabolism)
• Computational Biology
• Datasets as Topic
• Feasibility Studies
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Regulatory Networks (drug effects)
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Lung (pathology)
• Lung Neoplasms (diagnosis, drug therapy, genetics, mortality)
• Male
• Middle Aged
• Neoplasm Staging
• Oligonucleotide Array Sequence Analysis
• Prognosis
• Protein Interaction Maps (genetics)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Protein Serine-Threonine Kinases (analysis, antagonists & inhibitors, metabolism)
• Protein-Tyrosine Kinases (analysis, antagonists & inhibitors, metabolism)