Evaluation of KIF23 variant 1 expression and relevance as a novel prognostic factor in patients with hepatocellular carcinoma

Abstract

BackgroundKIF23 (kinesin family member 23) is a kinesin-like motor protein and plays an important role in cytokinesis. In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that KIF23 was upregulated in HCC tissues. At present, much less is known about its expression and functions in tumor cells. In this work, we aimed to investigate the expression of KIF23 in HCC and the correlation between its expression and clinical features.MethodsTotal RNA was extracted from 16 HCC and paired adjacent non-cancerous tissues. The expressions of the two KIF23 splice variants (KIF23 V1 and KIF23 V2) in normal and HCC tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Polyclonal antibody specific to KIF23 V1 was prepared, and the specificity of the antibody was confirmed by siRNA knockdown and Western blotting experiments. KIF23 protein expression in HCC was examined by immunohistochemistry staining with anti-KIF23 V1 or anti-KIF23 (commercially available for recognizing both KIF23 V1 and V2) antibodies, respectively. Univariate and Multivariate Cox regression analyses were used to determine the correlation between KIF23 protein expression and overall survival of HCC patients.ResultsThe two splicing variants of KIF23 mRNA were not detected in normal liver tissue by RT-PCR, but they were aberrantly expressed in HCC tissues. Immunohistochemistry staining with anti-KIF23 V1 antibody revealed that KIF23 V1 was mainly distributed in the nucleus, whereas the positive staining signals were predominantly in the cytoplasm when using anti-KIF23 antibody, suggesting that KIF23 V2 might localize in the cytoplasm of HCC cells. KIF23 V1 protein was detected in 57.6 % (83/144) HCC patients and the mean H-score was 42, while KIF23 V2 was detected in 94.4 % (135/143) HCC samples and the mean H-score was 68. Follow-up study showed that HCC patients with expression of KIF23 V1 had a longer 5-year survival (p = 0.0052), however, expression of KIF23 V2 protein did not associate with 3- and 5-year survival.ConclusionIn this study we show for the first time that KIF23 V1 and V2 have different localizations in HCC cells. Furthermore, KIF23 V1 protein expression might be a marker of longer overall survival in HCC patients.

Identification of Prognostic Biomarkers and Correlation with Immune Infiltrates in Hepatocellular Carcinoma Based on a Competing Endogenous RNA Network

“…HCC patients with positive identified KIF V1 had a better overall 5-year survival rate than those with no KIF V1. However, there was no significant correlation between expression of KIF V2 and overall survival in patients [48,49]. These discoveries by Xiaotong et al conflicted with results in this study, indicating that additional investigations should be performed to further elucidate the role of KIF23 in the tumorigenesis of HCC [48].…”

“…However, there was no significant correlation between expression of KIF V2 and overall survival in patients [48,49]. These discoveries by Xiaotong et al conflicted with results in this study, indicating that additional investigations should be performed to further elucidate the role of KIF23 in the tumorigenesis of HCC [48]. MYBL2 (MYB proto-oncogene like 2) is included in the family of MYB transcription factors and was overexpressed in breast cancer.…”

NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection

“…ANLN has been reported to be associated with poorer prognosis in breast, 28 bladder 29 and colorectal cancers 30 while BIRC5, KIF23 and NUF2 have been reported to be functionally important for HCC cell growth. 15,31,32 Multivariate logistic regression identified NUF2 as the minimal biomarker sufficient to predict HCC early recurrence (Fig. 2b).…”

Peer Review #1 of "Identification of key genes and long non-coding RNA associated ceRNA networks in hepatocellular carcinoma (v0.2)"

“…Therefore, further in-depth studies should be undertaken to evaluate the function of KIF23 in HCC. (Sun et al 2015) HMGB2 overexpression was detected at both mRNA and protein levels in tumor tissues from HCC patients. It is associated with shorter OS, and is considered to be an independent prognostic factor.…”