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.

MAP4 acts as an oncogene and prognostic marker and affects radioresistance by mediating epithelial–mesenchymal transition in lung adenocarcinoma

“…MAP4 expression is ubiquitous in nonneural samples and plays a key role in microtubule assembly in human cells. Researchers found that the ratio of MAP4 to Stathmin mRNA in NSCLC tissues was higher than that in normal specimens, suggesting that this ratio may be a potential prognostic marker in NSCLC patients (Singharajkomron et al 2022 ). Luo et al studied the relationship between the mRNA transcript level and protein expression level of different MAPs and related prognosis in NSCLC patients (Stanton et al 2011 ).…”

Identification and verification of microtubule associated genes in lung adenocarcinoma

“…Previous research mainly focused on a single gene, but little literature described the characteristics of all MAGs. Singharajkomron 17 investigated the prognostic function of microtubule-associated proteins in lung cancer and distinguished six genes as biomarkers. Consistent with this, KIF4A was also identified as a biomarker in this research.…”

A Comprehensive Genetic Study of Microtubule-Associated Gene Clusters for Male Infertility in a Taiwanese Cohort

“…NEK2 (NIMA-related kinase 2) is involved in centrosome duplication, a key process that ensures the correct organization of the MT organizing center of the cell [26]. Accurate cell division is essential for proper sperm development.…”