Kinesin 18A expression: Clinical relevance to colorectal cancer progression

Abstract

Kif18A, a member of the kinesin superfamily of molecular motor proteins, is a microtubule depolymerase and a key regulator of chromosome congregation. Kif18A's role in cancer progression has not been well defined. Our hypothesis is that Kif18A has a role in the progression of colorectal cancer (CRC). To investigate this expression of Kif18A, mRNA was assessed by quantitative real-time PCR in 113 operative specimens of primary CRC. Kif18A was overexpressed and significantly (p < 0.0001) higher in CRC than in normal colon tissue. Kif18A overexpression in CRC significantly correlated with clinicopathologic factors such as tumor stage (p < 0.0001), lymphatic invasion (p 5 0.001), lymph node metastasis (p 5 0.01), venous invasion (p 5 0.002) and peritoneal dissemination (p 5 0.02), suggesting that it has a key role in CRC progression. In multivariate analysis, high Kif18A expression had independent significance for poorer overall survival after resection of CRC (p 5 0.037). To demonstrate Kif18A's role in CRC progression, we performed translational and in situ studies. Using in vitro studies on CRC cell lines, we evaluated Kif18A's role in proliferation, migration and invasion. CRC cells transfected with Kif18A cDNA demonstrated significant enhanced migration (p < 0.01) and invasion (p 5 0.018) compared to mock-transfected cells. When Kif18A was targeted with specific small interfering RNA, CRC cells had significantly reduced proliferation (p < 0.01), migration (p < 0.01) and invasion (p < 0.05). The in vitro and translational studies demonstrated that Kif18A expression is related to events of metastasis and is a significant factor for CRC progression.Colorectal cancer (CRC) is one of the most common solid cancers and is increasing in incidence worldwide.

Elevated expression of KIF18A enhances cell proliferation and predicts poor survival in human clear cell renal carcinoma

“…Furthermore, it has been confirmed that KIF18A plays critical roles in the modulation of motility and mitosis, suggesting that KIF18A acts as a critical regulator in cell transformation and carcinogenesis (15). Notably, several studies have indicated that KIF18A is involved in breast carcinogenesis and colorectal cancer progression (16,17). Moreover, KIF18A has also been identified as a potential biomarker of lung cancer and cholangiocarcinoma using proteomic analysis (18,19).…”

Clinicopathological relevance of kinesin family member 18A expression in invasive breast cancer

“…It has been reported that KIF18A is involved in breast, colorectal and hepatocellular cancers, and cholangiocarcinoma (21)(22)(23)(24). However, there is essentially no information regarding the clinical relevance of KIF18A in breast cancer patients.…”

Serum KIF5A, KIF18A, and p53 Autoantibody Concentrations as Potential Biomarkers of Asbestos Exposure

“…KIF18A has been shown to be essential in the congression of chromosomes and the accurate alignment of the spindle equator and to suppress kinetochore movements during mitosis [25]. KIF18A overexpression has been positively related to tumor size and clinical tumor-node-metastasis in hepatocellular carcinoma (HCC), tumor grade and metastasis in breast cancer, and tumor stage, lymphatic invasion, lymph node metastasis, venous invasion, and peritoneal dissemination in colorectal cancer (CRC) as well as poor clinical outcomes [16][17][18][19].…”

“…The optimal cutoff level for KIF5A and KIF18A protein concentrations was explored via several methods including: the mean KIF5A level among the unexposed individuals plus 2 standard deviations; the mean KIF18A level among the unexposed individuals minus 1 standard deviation, due to a large standard deviation (greater than half the mean value which would result in a negative concentration) among control KIF18A levels; the mean KIF18A level among the unexposed individuals plus 1 standard deviation; and empirically determined cutoffs utilizing ROC analyses. The direction of the cutoffs explored is due to the observed increase in serum KIF5A levels and decreased serum KIF18A levels observed in a subset of asbestos cancer patients from an occupationally exposed Finnish asbestosis cohort reported previously, as well as the observed increases in KIF18A expression reported in the literature above [16][17][18][19][20]. These assays have been demonstrated to be highly reproducible and to have high sensitivity (LLD<118 pg/mL) and specificity (no cross-reactivity between each specific KIF and known analogues).…”