Evaluating the Expression and Prognostic Value of Genes Encoding Microtubule-Associated Proteins in Lung Cancer.

Abstract

Microtubule-associated proteins (MAPs) play essential roles in cancer development. This study aimed to identify transcriptomic biomarkers among MAP genes for the diagnosis and prognosis of lung cancer by analyzing differential gene expressions and correlations with tumor progression. Gene expression data of patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) from the Cancer Genome Atlas (TCGA) database were used to identify differentially expressed MAP genes (DEMGs). Their prognostic value was evaluated by Kaplan-Meier and Cox regression analysis. Moreover, the relationships between alterations in lung cancer hallmark genes and the expression levels of DEMGs were investigated. The candidate biomarker genes were validated using three independent datasets from the Gene Expression Omnibus (GEO) database and by quantitative reverse transcription polymerase chain reaction (qRT-PCR) on clinical samples. A total of 88 DEMGs were identified from TCGA data. The 20 that showed the highest differential expression were subjected to association analysis with hallmark genes. Genetic alterations in TP53, EGFR, PTEN, NTRK1, and PIK3CA correlated with the expression of most of these DEMGs. Of these, six candidates-NUF2, KIF4A, KIF18B, DLGAP5, NEK2, and LRRK2-were significantly differentially expressed and correlated with the overall survival (OS) of the patients. The mRNA expression profiles of these candidates were consistently verified using three GEO datasets and qRT-PCR on patient lung tissues. The expression levels of NUF2, KIF4A, KIF18B, DLGAP5, NEK2, and LRRK2 can serve as diagnostic biomarkers for LUAD and LUSC. Moreover, the first five can serve as prognostic biomarkers for LUAD, while LRRK2 can be a prognostic biomarker for LUSC. Our research describes the novel role and potential application of MAP-encoding genes in clinical practice.

• Authors: Natsaranyatron Singharajkomron, Varalee Yodsurang, Suthasinee Seephan, Sakkarin Kungsukool, Supinda Petchjorm, Nara Maneeganjanasing, Warunyu Promboon, Wadsana Dangwilailuck, Varisa Pongrakhananon
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 23 (Nov 25 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36499051 (Publication Type: Journal Article)

Chemical References

• Microtubule-Associated Proteins
• Biomarkers, Tumor
• KIF4A protein, human
• Kinesins
• NEK2 protein, human
• NIMA-Related Kinases
• KIF18B protein, human

Topics

• Humans
• Prognosis
• Microtubule-Associated Proteins (genetics)
• Biomarkers, Tumor (genetics)
• Lung Neoplasms (diagnosis, genetics, pathology)
• Adenocarcinoma of Lung (genetics, pathology)
• Carcinoma, Non-Small-Cell Lung (genetics)
• Carcinoma, Squamous Cell (diagnosis, genetics, pathology)
• Gene Expression Regulation, Neoplastic
• Kinesins (genetics)
• NIMA-Related Kinases