Kinesin family member 2A high expression correlates with advanced tumor stages and worse prognosis in non-small cell lung cancer patients

Abstract

Background: This present study was to explore the association of kinesin family member 2A (KIF2A) expression with clinicopathological features and survival profiles, and the effect of KIF2A on cell proliferation and chemosensitivity in non-small cell lung cancer (NSCLC).

Methods: Tumor and paired adjacent specimens were collected from 380 patients with NSCLC underwent resection for immunohistochemistry assay of KIF2A expression. In vitro, the effect of KIF2A on cell proliferation, chemosensitivity to cisplatin/vinorelbine was detected via KIF2A plasmids transfection into NCI-H1299 NSCLC cells.

Results: Kinesin family member 2A expression was upregulated in tumor tissues compared with adjacent tissues, and tumor tissue KIF2A high expression was associated with higher pathological grade (P < .001), larger tumor size (P = .021), lymph node metastasis (P = .044), and increased tumor-node-metastasis stage (P = .001). As for survival profiles, disease-free survival (P < .001) and overall survival (P < .001) were worse in patients with KIF2A high expression compared with those with KIF2A low expression. Multivariate Cox's regression exhibited that KIF2A high expression was an independent predictive factor for lower DFS (P < .001) and OS (P < .001). In vitro, KIF2A promoted proliferation and decreased chemosensitivity to cisplatin but not vinorelbine in NCI-H1299 NSCLC cells.

Conclusions: The correlation of KIF2A expression with tumor features, survival, and its cellular function implies its potential as a prognostic biomarker and a treatment target in NSCLC.

Keywords: cell proliferation; chemosensitivity; clinical features; kinesin family member 2A; non-small cell lung cancer.

Figure 1

Expression of KIF2A in NSCLC tumor tissues and adjacent tissues. Examples of IHC images about KIF2A high expression in tumor tissues (*200; *100) and KIF2A low expression in adjacent tissues (*200; * 100). IHC, immunohistochemistry; KIF2A, kinesin family member 2A; NSCLC, non‐small cell lung cancer

Figure 2

Correlation of KIF2A expression with DFS and OS. Comparison of DFS between patients with KIF2A high expression and low expression (A). Comparison of OS between patients with KIF2A high expression and low expression (B). The survivals for NSCLC patients were exhibited by Kaplan‐Meier curve, and the comparison of survival between patients with KIF2A high expression and low expression was performed by log‐rank test. P < .05 was considered significant. DFS, disease‐free survival; KIF2A, kinesin family member 2A; NSCLC, non‐small cell lung cancer; OS, overall survival

Figure 3

Effect of KIF2A on cell proliferation and chemosensitivity. Comparison of cell proliferation between NC(+) and KIF2A(+), between NC(−) and KIF2A(−) (A). Comparison of relative cell viability between NC(+) and KIF2A(+), between NC(−) and KIF2A(−) in 1, 2, 4, 8, 16, and 32 μmol/L cisplatin‐treated cells (B). Comparison of relative cell viability between NC(+) and KIF2A(+), between NC(−) and KIF2A(−) in 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 μmol/L vinorelbine‐treated cells (C). Comparison of IC₅₀ of cisplatin and vinorelbine between NC(+) and KIF2A(+) as well as between NC(−) and KIF2A(−) (D). Comparison was determined by the unpaired t test. IC₅₀ was calculated by probit regression model. P < .05 was considered significant. *P < .05, **P < .01. IC₅₀, 50% inhibitory concentration; KIF2A(+), KIF2A over‐expression group; NC(+), over‐expression negative control group; KIF2A(−), KIF2A knockdown group; and NC(−), knockdown negative control group