High kinesin family member 18A expression correlates with poor prognosis in primary lung adenocarcinoma

Abstract

Background: Lung adenocarcinoma (LUAD) is the most prevalent pathological subtype of lung cancer. Kinesin family member 18A (KIF18A) plays an important role in tumorigenesis. Its roles in breast cancer, colorectal cancer, and other tumors have been demonstrated; however, studies of KIF18A in LUAD are limited. This study aimed to determine the role of KIF18A in LUAD progression and prognostic prediction.

Methods: KIF18A expression was examined in LUAD cells and tissues by immunohistochemistry and Western blotting. Cell proliferation assay was performed to study the role of KIF18A in LUAD cells. Correlations between KIF18A expression and clinicopathological features were analyzed. The role of KIF18A in LUAD prognosis was evaluated using data from The Cancer Genome Atlas (TCGA).

Results: KIF18A expression was increased in tumor cells and tissues. Downregulation of KIF18A expression resulted in the suppression of cancer cell proliferation in in vitro assays, and was particularly related to poor tumor differentiation, big tumor size, lymph node metastasis, and more advanced tumor stage. In the TCGA dataset, high KIF18A messenger RNA expression was associated with poor disease-free and overall survival in patients with LUAD. In addition, multivariate analysis indicated that KIF18A is an independent prognostic factor of disease-free and overall survival in LUAD.

Conclusions: Collectively, our results demonstrate that KIFl8A is highly expressed in LUAD. KIFl8A plays an important role in LUAD cell proliferation, but is a poor prognostic factor.

Keywords: Bioinformatics; kinesin family member 18A (KIF18A); lung adenocarcinoma (LUAD); prognosis.

Figure 1

Expression level of kinesin family member (18A KIF18A) in lung adenocarcinoma (LUAD). (a) KIF18A messenger RNA expression was higher in LUAD tissues than in normal lung tissues, (The Cancer Genome Atlas and Genotype‐Tissue Expression databases). (b) KIF18A expression in different LUAD cells. (c) Immunostaining of KIF18A in LUAD and adjacent normal lung tissues showed different expression levels. Magnification 100 × (left) and 200 × (right). GAPDH, glyceraldehyde 3‐phosphate dehydrogenase.

Figure 2

Kinesin family member (18A KIF18A) regulates the proliferation of lung adenocarcinoma (LUAD) cells in vitro. (a) Confirmation of RNA interference against KIF18A in A549 cells by Western blot. (b) Western blot analysis shows Ki67 and PCNA expression in A549 cells transfected with the indicated small interfering RNA (siRNA). Glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) was used as an internal control. (c) A Cell Counting Kit‐8 assay was performed to determine the proliferation of A549 cells in response to knocked down KIF18A. Scrambled siRNA, siKIF18A. (d) Representative image and numbers of colony formation assays of A549 cells transfected with KIF18A siRNA or control plasmids.

Figure 3

Kaplan–Meier analysis of kinesin family member 18A (KIF18A) expression in lung adenocarcinoma (LUAD) patients (The Cancer Genome Atlas) and survival. Protein levels showed that KIF18A played a prognostic role in (a) disease‐free survival and (b) overall survival. Low KIF18A TPM, high KIF18A TPM, Low censored, high censored. Low KIF18A TPM, high KIF18A TPM, low censored, high censored. TPM, Transcripts per kilobase of exonmodel per million.