Genome‑wide investigation of the clinical significance and prospective molecular mechanisms of kinesin family member genes in patients with lung adenocarcinoma

Abstract

The current study aimed to identify the potential clinical significance and molecular mechanisms of kinesin (KIF) family member genes in lung adenocarcinoma (LUAD) using genome-wide RNA sequencing (RNA-seq) datasets derived from The Cancer Genome Atlas (TCGA) database. Clinical parameters and RNA-seq data of patients with LUAD from the TCGA database enabled the assessment of the clinical significance of KIF genes, while the potential mechanisms of their interactions in LUAD were investigated by gene set enrichment analysis (GSEA). A gene signature with potential prognostic value was constructed via a stepwise multivariable Cox analysis. In total, 23 KIF genes were identified to be differentially expressed genes (DEGs) between the LUAD tumor and adjacent non-cancerous tissues. Of these, 8 differentially expressed KIF genes were strongly found to be strongly associated with the overall survival of patients with LUAD. Three of these genes were found to be able to be grouped as a potential prognostic gene signature. Patients with higher risk scores calculated using this gene signature were found to have a markedly higher risk of mortality (adjusted P=0.003; adjusted HR, 1.576; 95% CI, 1.166–2.129). Time-dependent receiver operating characteristic analysis indicated that this prognostic signature was able to accurately predict patient prognosis with an area under curve of 0.636, 0.643,0.665, 0.670 and 0.593 for the 1-, 2-, 3-, 4- and 5-year survival, respectively. This prognostic gene signature was identified as an independent risk factor for LUAD and was able to more accurately predict prognosis in comparison to other known clinical parameters, as shown via comprehensive survival analysis. GSEA enrichment revealed that that KIF14, KIF18B and KIF20A mediated basic cell physiology through the regulation of the cell cycle, DNA replication, and DNA repair biological processes and pathways. On the whole, the findings of this study identified 23 KIF genes that were DEGs between LUAD tumor and adjacent non-cancerous tissues. In total, 8 of these genes had the potential to function as prognostic and diagnostic biomarkers in patients with LUAD.

Identification of KIF18B as a Hub Candidate Gene in the Metastasis of Clear Cell Renal Cell Carcinoma by Weighted Gene Co-expression Network Analysis

“…Another research (Xiang X. H. et al, 2019) reveals that KIF18B is down-regulated in senescent cells and abnormally up-regulated in hepatocellular carcinoma cells, and the overexpression of KIF18B was a risk factor for poorer survival. Other reports have drawn similar conclusions in lung adenocarcinoma (Zhang et al, 2019) and bladder cancer (Pan et al, 2019). Accordingly, we suppose the high utilization value of KIF18B as a biomarker for prognosis evaluating and a specific target for precise treatment in ccRCC.…”

The High Expression of PTPRH Is Associated with Poor Prognosis of Human Lung Adenocarcinoma

“…The occurrence of LUAD is associated with genetic factors, environmental factors, and other external factors (including smoking), among which genetic factors can be used as more objective biomarkers or indicators for diagnosis, treatment, and prognosis of LUAD [ 14 ]. The continuous development of high-throughput sequencing technology and database provides great convenience for verification of these biomarkers.…”

Prognostic Nomogram Based on Circular RNA-Associated Competing Endogenous RNA Network For Patients With Lung Adenocarcinoma

“…As a mitotic kinesin, KIF14 has been reported to serve oncogenic roles through the regulation of the cell cycle, DNA replication and DNA repair biological processes in a variety of malignancies, such as colorectal cancer [30], ovarian cancer [31], gastric cancer [32], prostate cancer [33], and so on. Zhang et al had con rmed that KIF14 was notably up-regulated in tumor tissues of LUAD and the expression levels of the KIF14 exhibited a strongly correlation with OS [34]. PRR11, located on chromosome 17q22, has been reported to be closely associated with cell cycle progression and was also demonstrated to participate in various biological processes in tumor cells, including cell invasion, migration and proliferation, by acting as an oncogene [35][36][37][38].…”