Prognostic Impact and Functional Annotations of KIF11 and KIF14 Expression in Patients with Colorectal Cancer

Abstract

Genomic instability (GIN) has an important contribution to the pathology of colorectal cancer (CRC). Therefore, we selected mitosis and cytokinesis kinesins, KIF11 and KIF14, as factors of potential clinical and functional value in CRC, as their aberrant expression has been suspected to underlie GIN. We examined the expression and the prognostic and biological significance of KIF11 and KIF14 in CRC via in-house immunohistochemistry on tissue microarrays, public mRNA expression datasets, as well as bioinformatics tools. We found that KIF11 and KIF14 expression, at both the protein and mRNA level, was markedly altered in cancer tissues compared to respective controls, which was reflected in the clinical outcome of CRC patients. Specifically, we provide the first evidence that KIF11 protein and mRNA, KIF14 mRNA, as well as both proteins together, can significantly discriminate between CRC patients with better and worse overall survival independently of other relevant clinical risk factors. The negative prognostic factors for OS were high KIF11 protein, high KIF11 protein + low KIF14 protein, low KIF11 mRNA and low KIF14 mRNA. Functional enrichment analysis revealed that the gene sets related to the cell cycle, DNA replication, DNA repair and recombination, among others, were positively associated with KIF11 or KIF14 expression in CRC tissues. In TCGA cohort, the positive correlations between several measures related to GIN and the expression of KIFs were also demonstrated. In conclusion, our results suggest that CRC patients can be stratified into distinct risk categories by biological and molecular determinants, such as KIF11 and KIF14 expression and, mechanistically, this is likely attributable to their role in maintaining genome integrity.

Characterization of Cell Cycle-Related Competing Endogenous RNAs Using Robust Rank Aggregation as Prognostic Biomarker in Lung Adenocarcinoma

“…MKI67, a marker gene in the cell cycle, also has been reported with prognostic value in NSCLC (62) and breast cancer (63). Furthermore, the prognostic value of KIF11 has been reported in oral cancer (64) and colorectal cancer (65).…”

Role of kinesin family member 14 in disease monitoring and prognosis in patients with gastrointestinal cancer

“…As a crucial member of the kinesin family, KIF14 has been reported to be a regulator of tumor development and progression in previous studies and could also be a potential biomarker in the management of patients with cancer ( 24 , 25 ). A prior study revealed that KIF14 inhibition using small interfering (si)RNA could repress proliferation and enhance apoptosis in medulloblastoma cells, while KIF14 inhibition using short hairpin RNA could suppress cell viability, colony formation, invasion, migration and tumor sphere formation in medulloblastoma cells ( 18 ).…”

“…In addition, KIF14 was upregulated in tumor tissues and could predict unfavorable outcomes in patients with ovarian cancer ( 29 ). These aforementioned studies indicated that in numerous types of cancer, KIF14 might be a promoter of cancer progression, and could be a potential biomarker for prognosis ( 21 , 24 – 29 ).…”

SPDL1 Is an Independent Predictor of Patient Outcome in Colorectal Cancer

“…Histologically normal tissues adjacent to the tumor were available for 27 cases, and these constituted the control group. The same cohort of patients was previously described [36]. This study was carried out in accordance with the guidelines of the Declaration of Helsinki.…”

“…Immunohistochemical (IHC) staining was performed on tissue microarrays, the construction of which was described in our previous reports [36,37]. SPDL1 protein was stained in BenchMark ® ULTRA (Roche Diagnostics/Ventana Medical Systems, Tucson, AZ, USA) using ultraView Universal DAB Detection Kit (Roche Diagnostics/Ventana, Tucson, AZ, USA) according to the previously validated protocol [7].…”