Abstract
BackgroundKIF15 plays a vital role in many biological processes and has been reported to influence the occurrence and development of certain human cancers. However, there are few systematic evaluations on the role of KIF15 in human cancers, and the role of KIF15 in the diagnosis and prognosis of nasopharyngeal carcinoma (NPC) also remains unexplored. Therefore, this study aimed to conduct a pan-cancer analysis of KIF15 and evaluate its diagnostic and prognostic potential in NPC.MethodsThe expression pattern, prognostic value, molecular function, tumor mutation burden, microsatellite instability, and immune cell infiltration of KIF15 were examined based on public databases. Next, the diagnostic value of KIF15 in NPC was analyzed using the Gene Expression Omnibus (GEO) database and immunohistochemistry (IHC). Kaplan–Meier curves, Cox regression analyses, and nomograms were used to evaluate the effects of KIF15 expression on NPC prognosis. Finally, the effect of KIF15 on NPC was explored by in vitro experiments.ResultsThe expression of KIF15 was significantly upregulated in 20 out of 33 cancer types compared to adjacent normal tissue. Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analysis showed that KIF15 could participate in several cancer-related pathways. The increased expression level of KIF15 was correlated with worse clinical outcomes in many types of human cancers. Additionally, KIF15 expression was related to cancer infiltration of immune cells, tumor mutation burden, and microsatellite instability. In the analysis of NPC, KIF15 was significantly upregulated based on the GEO database and immunohistochemistry. A high expression of KIF15 was negatively associated with the prognosis of patients with NPC. A nomogram model integrating clinical characteristics and KIF15 expression was established, and it showed good predictive ability with an area under the curve value of 0.73. KIF15 knockdown significantly inhibited NPC cell proliferation and migration.ConclusionsOur findings revealed the important and functional role of KIF15 as an oncogene in pan-cancer. Moreover, high expression of KIF15 was found in NPC tissues, and was correlated with poor prognosis in NPC. KIF15 may serve as a potential therapeutic target in NPC treatment.
Highlights
Cancer has become the leading cause of morbidity and mortality in low- and high-income countries around the world [1]
We evaluated the correlation between KIF15 and the survival results (OS, Relapse-Free Survival (RFS), and Distant metastasis-free survival (DMFS)) by the pooled hazard ratios (HRs) and 95% confidence intervals (CIs)
In The Cancer Genome Atlas (TCGA) database, KIF15 was upregulated in 20 cancer types, including BLCA, BRCA, CESC, CHOL, COAD, ESCA, GBM, HNSC, KICH, KIRC, LIHC, LUAD, LUSC, PCPG, PRAD, READ, SARC, STAD, THCA and UCEC (Figure 1A)
Summary
Cancer has become the leading cause of morbidity and mortality in low- and high-income countries around the world [1]. Despite great advances in diagnostic and therapeutic methods of treating cancer in recent years, the survival outcome and quality of life of patients remains unsatisfactory [3]. Among all types of cancers, nasopharyngeal carcinoma (NPC) is endemic to southeast Asia, north Africa, and southern China. Advanced NPC had worse clinical outcomes due to delayed diagnosis and distant metastasis are the critical factors for treatment failure [7]. It is necessary to identify novel biomarkers and investigate the molecular mechanisms for improving early diagnosis and prognosis of NPC. There are few systematic evaluations on the role of KIF15 in human cancers, and the role of KIF15 in the diagnosis and prognosis of nasopharyngeal carcinoma (NPC) remains unexplored. This study aimed to conduct a pan-cancer analysis of KIF15 and evaluate its diagnostic and prognostic potential in NPC
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