Integrative Pan-Cancer Analysis of KIF15 Reveals Its Diagnosis and Prognosis Value in Nasopharyngeal Carcinoma

Abstract

Background: KIF15 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.

Methods: The 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.

Results: The 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.

Conclusions: Our 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.

Keywords: KIF15; diagnosis; nasopharyngeal carcinoma; pan-cancer analysis; prognosis.

Figure 1

The expression level of KIF15 in pan-cancer. (A) Differential expression of KIF15 between tumor and normal tissues of KIF15 in TCGA. (B) Differential expression of KIF15 between tumor and normal tissues of KIF15 in Oncomine. (C) Differential expression of KIF15 between tumor and normal tissues of KIF15 in Kaplan–Meier plotter. *P < 0.05; **P < 0.01 and ***P < 0.001.

Figure 2

Correlation of KIF15 mRNA expression and different pathological stages of certain cancers in TCGA.

Figure 3

The prognosis value of KIF15 of differ cancers using Univariate Cox proportional hazards models. (A) Overall survival (OS). (B) Disease-free survival (DFI). (C) Disease-specific survival (DSS). (D) Progression-free interval (PFI).

Figure 4

The prognostic value of KIF15 in different cancers using Kaplan–Meier method. (A) Overall survival (OS). (B) Disease-free survival (DFI). (C) Disease-specific survival (DSS). (D) Progression-free interval (PFI). (E) OS curve of KIF15 in all cancer based on GEPIA. (F) Disease-free survival (DFS) curve of KIF15 in all cancer based on GEPIA.

Figure 5

Functional analysis of KIF15 and relevant genes. (A) Protein–protein interaction (PPI) network display the top 100 relevant genes of KIF15. (B) Gene Oncology (GO) analysis of KIF15 and relevant genes. (C) Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of KIF15 and relevant genes.

Figure 6

The alteration frequency with mutation type of KIF15 in different cancer types from TCGA database.

Figure 7

Association of KIF15 mRNA expression with tumor mutational burden (TMB), microsatellite instability (MSI) and immune genes. (A) A radar map shows the relationship of KIF15 and TMB. (B) A radar map shows the relationship of KIF15 and MSI. (C) Heatmap shows the relationship of KIF15 and immune genes. *P < 0.05; **P < 0.01 and ***P < 0.001.

Figure 8

The expression of KIF15 in nasopharyngeal carcinoma (NPC) and normal tissues were investigated by GEO database. (A–C) KIF15 was significantly upregulated in NPC tissue in three datasets. (D–F) The diagnostic operating characteristic (ROC) curves of KIF15 in NPC and normal tissues in three datasets.

Figure 9

Preliminary experimental verification of KIF15 in patients with nasopharyngeal carcinoma (NPC). (A) Immunohistochemical analysis of KIF15 protein expression between nasopharyngeal carcinoma (NPC) and normal tissues (200×). (B) Kaplan–Meier survival curves for KIF15 in NPC.

Figure 10

Nomogram for predicting the prognosis of NPC patient. (A) Nomogram. (B, C) 3-year and 5-year calibration curves. (D) Operating characteristic (ROC) curves for the mode. (E) Survival curve of high-risk and low-risk groups.

Figure 11

Enrichment plots of GSEA from GSE12452 dataset. (A–C) KIF15 related signaling pathways in c2.cp.kegg.v7.1.symbols.gmt.

Figure 12

Effect of KIF15 in NPC cell proliferation and migration. (A) qRT-PCR analysis of KIF15 expression level in normal and NPC cell lines. (B) qRT-PCR analysis confirmed the knockdown efficacy of KIF15 in NPC cell line CNE1. (C, D) CCK-8 and colony formation assay were applied to examine the proliferation ability of KIF15 knockdown cells. (E, F) Wound-healing and transwell assay employed to detect the migration ability of KIF15 knockdown cells. **P < 0.01 and ***P < 0.001.