Monitoring the Outcomes of Systemic Chemotherapy Including Immune Checkpoint Inhibitor for HER2-Positive Metastatic Gastric Cancer by Liquid Biopsy

Purpose@#For precision medicine, exploration and monitoring of molecular biomarkers are essential. However, in advanced gastric cancer (GC) with visceral lesions, an invasive procedure cannot be performed repeatedly for the follow-up of molecular biomarkers. @*Materials and Methods@#To verify the clinical implication of serial liquid biopsies targeting circulating tumor DNA (ctDNA) on treatment response, we conducted targeted deep sequencing for serially collected ctDNA of 15 HER2-positive metastatic GC patients treated with anti-PD-1 inhibitor in combination with standard systemic treatment. @*Results@#In the baseline ctDNAs, 14 patients (93%) harbored more than one genetic alteration. A number of mutations in wellknown cancer-related genes, such as KRAS and PIK3CA, were identified. Copy number alterations were identified in eight GCs (53.3%), and amplification of the ERBB2 gene (6/15, 40.0%) was the most recurrent. When we calculated the mean variant allele frequency (VAF) of mutations in each ctDNA as the molecular tumor burden index (mTBI), the mTBI trend was largely consistent with the VAF profiles in both responder and non-responder groups. Notably, in the longitudinal analysis of ctDNA, mTBI provided 2–42 weeks (mean 13.4 weeks) lead time in the detection of disease progression compared to conventional follow-up with CT imaging. @*Conclusion@#Our data indicate that the serial genetic alteration profiling of ctDNA is feasible to predict treatment response in HER2-positive GC patients in a minimally invasive manner. Practically, ctDNA profiles are useful not only for the molecular diagnosis of GC but also for the selection of GC patients with poor prognosis for systemic treatment (ClinicalTrials.gov identifier:NCT02901301).

Distal Femur Fractures Treated with Distal Femoral Locking Plate Fixation:A Retrospective Study of One Year Mortality and Risk Factors

Purpose@#This study examined the one-year mortality after locking plate fixation for distal femur fractures and the risk factors related to death. @*Materials and Methods@#From July 2011 to June 2020, 128 patients who underwent locking plate fixation for distal femur fractures were analyzed retrospectively. Epidemiologic information of the patients, characteristics related to fracture and surgery, and death were investigated. The risk factors related to death were investigated using Cox analysis, and a subgroup analysis was also performed based on the age of 65 years. @*Results@#The one-year mortality rate after locking plate fixation for distal femur fractures was 3.9%, and the mortality rates in patients younger than 65 years and older than 65 years were 0% and 6.7%, respectively. There were no significant risk factors related to death in the total population. On the other hand, in patients aged 65 years or older, however, high-energy fracture and high comorbidity index increased the risk of death after surgery by 6.9-fold and 1.9-fold, respectively. @*Conclusion@#The one-year mortality rate for the total patients was 3.9%, but the mortality rate for patients over 65 years of age increased to 6.7%. High-energy fractures and high comorbidity index were risk factors related to death after surgery for distal femur fractures in patients aged 65 years or older.

Development of an RNA sequencing panel to detect gene fusions in thyroid cancer

In addition to mutations and copy number alterations, gene fusions are commonly identified in cancers. In thyroid cancer, fusions of important cancer-related genes have been commonly reported; however, extant panels do not cover all clinically important gene fusions. In this study, we aimed to develop a custom RNA-based sequencing panel to identify the key fusions in thyroid cancer. Our ThyChase panel was designed to detect 87 types of gene fusion. As quality control of RNA sequencing, five housekeeping genes were included in this panel. When we applied this panel for the analysis of fusions containing reference RNA (HD796), three expected fusions (EML4-ALK, CCDC6-RET, and TPM3-NTRK1) were successfully identified. We confirmed the fusion breakpoint sequences of the three fusions from HD796 by Sanger sequencing. Regarding the limit of detection, this panel could detect the target fusions from a tumor sample containing a 1% fusion-positive tumor cellular fraction. Taken together, our ThyChase panel would be useful to identify gene fusions in the clinical field.

PAIVS: prediction of avian influenza virus subtype

Highly pathogenic avian influenza (HPAI) viruses have caused severe respiratory disease and death in poultry and human beings. Although most of the avian influenza viruses (AIVs) are of low pathogenicity and cause mild infections in birds, some subtypes including hemagglutinin H5 and H7 subtype cause HPAI. Therefore, sensitive and accurate subtyping of AIV is important to prepare and prevent for the spread of HPAI. Next-generation sequencing (NGS) can analyze the full-length sequence information of entire AIV genome at once, so this technology is becoming a more common in detecting AIVs and predicting subtypes. However, an analysis pipeline of NGS-based AIV sequencing data, including AIV subtyping, has not yet been established. Here, in order to support the pre-processing of NGS data and its interpretation, we developed a user-friendly tool, named prediction of avian influenza virus subtype (PAIVS). PAIVS has multiple functions that support the pre-processing of NGS data, reference-guided AIV subtyping, de novo assembly, variant calling and identifying the closest full-length sequences by BLAST, and provide the graphical summary to the end users.

PAIVS: prediction of avian influenza virus subtype

Highly pathogenic avian influenza (HPAI) viruses have caused severe respiratory disease and death in poultry and human beings. Although most of the avian influenza viruses (AIVs) are of low pathogenicity and cause mild infections in birds, some subtypes including hemagglutinin H5 and H7 subtype cause HPAI. Therefore, sensitive and accurate subtyping of AIV is important to prepare and prevent for the spread of HPAI. Next-generation sequencing (NGS) can analyze the full-length sequence information of entire AIV genome at once, so this technology is becoming a more common in detecting AIVs and predicting subtypes. However, an analysis pipeline of NGS-based AIV sequencing data, including AIV subtyping, has not yet been established. Here, in order to support the pre-processing of NGS data and its interpretation, we developed a user-friendly tool, named prediction of avian influenza virus subtype (PAIVS). PAIVS has multiple functions that support the pre-processing of NGS data, reference-guided AIV subtyping, de novo assembly, variant calling and identifying the closest full-length sequences by BLAST, and provide the graphical summary to the end users.

Potential Oncogenic Role of the Papillary Renal Cell Carcinoma Gene in Non-Small Cell Lung Cancers

PURPOSE: Papillary renal cell carcinoma (PRCC) gene, which located in 1q23.1, is recurrently amplified in non-small cell lung cancer (NSCLC). However, it is unknown whether PRCC is overexpressed in primary NSCLCs and whether PRCC overexpression contributes to lung tumorigenesis. In this study, we aimed to identify the profiles of PRCC expression in Korean NSCLC patients and to elucidate the role of PRCC overexpression on lung tumorigenesis. MATERIALS AND METHODS: We performed immunohistochemistry analysis with a tissue array containing 161 primary NSCLCs. Small interfering RNA targeting PRCC (siPRCC) was transfected into two lung cancer cell lines (NCI-H358 and A549), after which tumor growth, migration, and invasion were observed. Expressions of cell proliferation-, cell cycle-, and metastasis-related molecules were examined by Western blot analysis. We also explored the in vivo effect of PRCC silencing. RESULTS: PRCC overexpression was recurrently observed in NSCLCs (95/161, 59%). After siPRCC treatment, tumor cell proliferation, colony formation, and anchorage independent growth were significantly reduced (p < 0.001 for all three effects). Migration and invasiveness were also significantly repressed (p < 0.001 for both effects). Reflecting cell proliferation, cell cycle, and metastasis, the expressions of Ki67, cyclin D1, AKT-1, pAKT, NF-kB p65, vimentin and CXCL-12 were found to be downregulated. Through mouse xenograft analysis, we confirmed that PRCC silencing significantly repressed a xenograft tumor mass in vivo (p < 0.001). CONCLUSION: The present data provide evidence that PRCC overexpression is involved in the tumorigenesis and progression of lung cancer.

A Brain Atlas of the Long Arm Octopus, Octopus minor

Cephalopods have the most advanced nervous systems and intelligent behavior among all invertebrates. Their brains provide comparative insights for understanding the molecular and functional origins of the human brain. Although brain maps that contain information on the organization of each subregion are necessary for a study on the brain, no whole brain atlas for adult cephalopods has been constructed to date. Here, we obtained sagittal and coronal sections covering the entire brain of adult Octopus minor (Sasaki), which belongs to the genus with the most species in the class Cephalopoda and is commercially available in East Asia throughout the year. Sections were stained using Hematoxylin and Eosin (H&E) to visualize the cellular nuclei and subregions. H&E images of the serial sections were obtained at 30~70-µm intervals for the sagittal plain and at 40~80-µm intervals for the coronal plain. Setting the midline point of the posterior end as the fiducial point, we also established the distance coordinates of each image. We found that the brain had the typical brain structure of the Octopodiformes. A number of subregions were discriminated by a Hematoxylin-positive layer, the thickness and neuronal distribution pattern of which varied markedly depending upon the region. We identified more than 70 sub-regions based on delineations of representative H&E images. This is the first brain atlas, not only for an Octopodiformes species but also among adult cephalopods, and we anticipate that this atlas will provide a valuable resource for comparative neuroscience research.

Revision Anterior Cruciate Ligament Reconstruction: Analysis of the Causes of Failure, Associated Injuries and Clinical Results / 대한정형외과학회잡지

PURPOSE: The aim of this study was to analyze the causes of failure after a primary anterior cruciate ligament reconstruction (ACLR), associated injuries, and the clinical results of revision ACLR. MATERIALS AND METHODS: This study evaluated 46 patients (46 knees), who were followed at least two years after revision ACLR. The evaluations included the causes of failure after primary ACLR, associated injuries, 2000 International Knee Documentation Committee (IKDC) subjective knee scores, Lachman test, Pivot shift test, and KT-1000 arthrometer measurement. RESULTS: The most common cause of failure was trauma (27 patients, 58.7%) and 19 failures (19 patients, 41.3%) were caused using an inappropriate surgical technique. The associated injuries were meniscus tears in 29 cases (63.0%) and articular cartilage injuries of Outerbridge grade II to IV in 19 cases (41.3%). The IKDC scores, Lachman test, Pivot shift test, and KT-1000 arthrometer measurements were improved significantly at the final follow-up. CONCLUSION: The most common cause of failure after primary ACLR was trauma. One stage revision ACLR resulted in relatively satisfactory stability but less satisfactory clinical function than the primary reconstruction, as reported previously, which is believed to be due to the more associated injuries.

Mutational signatures and chromosome alteration profiles of squamous cell carcinomas of the vulva

Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (−)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (−) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (−) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (−) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (−) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (−) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (−)) SCCs. Our data indicate that HPV (+) and HPV (−) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (−) vulvar SCCs and may aid in the development of clinical treatment strategies.

Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues

Patient-derived xenograft (PDX) models are useful tools for tumor biology research and testing the efficacy of candidate anticancer drugs targeting the druggable mutations identified in tumor tissue. However, it is still unknown how much of the genetic alterations identified in primary tumors are consistently detected in tumor tissues in the PDX model. In this study, we analyzed the genetic alterations of three primary colorectal cancers (CRCs) and matched xenograft tissues in PDX models using a next-generation sequencing cancer panel. Of the 17 somatic mutations identified from the three CRCs, 14 (82.4%) were consistently identified in both primary and xenograft tumors. The other three mutations identified in the primary tumor were not detected in the xenograft tumor tissue. There was no newly identified mutation in the xenograft tumor tissues. In addition to the somatic mutations, the copy number alteration profiles were also largely consistent between the primary tumor and xenograft tissue. All of these data suggest that the PDX tumor model preserves the majority of the key mutations detected in the primary tumor site. This study provides evidence that the PDX model is useful for testing targeted therapies in the clinical field and research on precision medicine.

Differential Diagnosis and Treatment of Cervical Spondylotic Myelopathy Mimicking Myelitis in an Adolescent Patient: A Case Report

STUDY DESIGN: Case report OBJECTIVES: This study introduces an interesting case of adolescent cervical myelopathy with atypical cervical magnetic resonance imaging (MRI) findings. A differential diagnosis was made, followed by successful surgical treatment. SUMMARY OF LITERATURE REVIEW: A careful differential diagnosis of high signal intensity on T2-weighted cervical MRI is necessary if there is no evidence of cervical stenosis. Recent reports have suggested that the differential diagnosis should be based on a comprehensive analysis of data, including brain MRI, a cerebrospinal fluid examination, and empirical steroid treatment. MATERIALS AND METHODS: A 17-year-old male patient complained of upper extremity weakness, gait disturbance, and decreased sensation in the upper extremity. Cervical spine MRI findings suggested C3/4 disc herniation, moderate cervical stenosis, and high signal intensity in the spinal cord. A differential diagnosis was made between cervical myelopathy and myelitis. RESULTS: Decompression and posterolateral fusion of C3/4 were performed in a 17-year-old patient with cervical myelopathy without significant cervical stenosis. Postoperatively, upper extremity sensation and weakness and gait disturbance showed improvement, and the Japanese Orthopedic Association score improved to 17 points at 6 months after surgery. CONCLUSIONS: In patients with cervical myelopathy showing high signal intensity on T2-weighted imaging without evident spinal stenosis, a differential diagnosis should be made between cervical myelopathy and myelitis; surgical decompression can be an effective treatment choice upon the diagnosis of cervical myelopathy.

Phenolic Compounds from the Leaves of Homonoia riparia and their Inhibitory Effects on Advanced Glycation End Product Formation

In a search for novel treatments for diabetic complications from natural resources, we found that the ethyl acetate-soluble fraction from the 80% ethanol extract of the leaves of Homonoia riparia has a considerable inhibitory effect on advanced glycation end product (AGE) formation. Bioassay-guided isolation of this fraction resulted in identification of 15 phenolic compounds (1 – 15). These compounds were evaluated in vitro for inhibitory activity against the formation of AGE. The majority of tested compounds, excluding ethyl gallate (15), markedly inhibited AGE formation, with IC₅₀ values of 2.2 – 89.9 µM, compared with that of the positive control, aminoguanidine (IC₅₀ = 962.3 µM). In addition, the effects of active isolates on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval zebrafish was investigated; (–)-epigallocatechin-3-O-gallate (6), corilagin (7), and desmanthine-2 (11) significantly decreased HG-induced dilation of hyaloid–retinal vessels compared with the HG-treated control group.

A Variant in RUNX3 Is Associated with the Risk of Ankylosing Spondylitis in Koreans

Ankylosing spondylitis (AS) is a chronic autoinflammatory disease that affects the spine and sacroiliac joints. Regarding its etiology, although HLA-B27 is known to be the strongest genetic factor of AS, much evidence suggests the potential contribution of non-MHC genes to the susceptibility to AS. Most of these non-MHC genes have been discovered in non-Asian populations; however, just some of them have been validated in Koreans. In this study, we aimed to identify additional AS-associated single-nucleotide polymorphism (SNP) candidates by replicating the candidate SNPs in Korean AS patients and healthy controls. For this, we selected three SNPs (rs11249215 in RUNX3, rs6556416 in IL12B, and rs8070463 in TBKBP1), which were previously reported as risk factors of AS but have not been studied in Koreans, and performed genotyping assays using a total of 1138 Korean samples (572 AS patients and 566 healthy controls). Of the three SNP candidates, one SNP in RUNX3 (rs11249215) was significantly associated with the risk of AS (odds ratio, 1.31; 95% confidence interval, 1.02 to 1.68, p = 0.03). These results will be helpful in elucidating the pathogenesis of AS and may be useful for developing AS risk prediction models in Koreans.

Status and compliance with standard open format of public open data in healthcare in Korea

In the era of government 3.0, the availability of open government-owned public data and data sharing with the private sector are important. We surveyed the status of public data openness in the healthcare domain and of compliance with the standard open data format based on the “5 stars of linked data” model. We examined healthcare data on the Open Data Portal (https://www.data.go.kr). We also surveyed data on the websites of the public institutions and state administrative agencies that provided healthcare data on the Portal. In terms of data on the Portal, all public institutions except the National Medical Center, the Korea Institute of Science and Technology Information, and the Korea Environment Corporation were found to have provided data in the 3-stars format corresponding to the Public Data Open Standard Maintenance Guide. All data provided by state administrative agencies met the 3-stars format. Only 2 institutions (the Health Insurance Review & Assessment Service and the Korea Health Industry Development Institute) released data in the 3-stars format on their websites. Among the major state administrative agencies providing data on the Portal, none released data in the 3-stars format on their websites. Government-owned data should be provided in a standard format both on the Open Data Portal and on data-holders' websites to facilitate communication and collaboration. Considering the huge potential of linked healthcare data from a single national health insurance system, providing open data in compliance with the standard open format will promote the opening and sharing of public data.

Circulating Tumor DNA in a Breast Cancer Patient's Plasma Represents Driver Alterations in the Tumor Tissue

Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy. In this study, we performed whole-exome sequencing for a breast cancer tissue and identified PTEN p.H259fs*7 frameshift mutation. In the plasma DNA (liquid biopsy) analysis by targeted NGS, the same variant initially identified in the tumor tissue was also detected with low variant allele frequency. This mutation was subsequently validated by digital polymerase chain reaction in liquid biopsy. Our result confirm that driver alterations identified in the tumor tissue were detected in liquid biopsy by targeted NGS as well, and suggest that a higher depth of sequencing coverage is needed for detection of genomic alterations in a liquid biopsy.

Validation of Customized Cancer Panel for Detecting Somatic Mutations and Copy Number Alterations

Accurate detection of genomic alterations, especially druggable hotspot mutations in tumors, has become an essential part of precision medicine. With targeted sequencing, we can obtain deeper coverage of reads and handle data more easily with a relatively lower cost and less time than whole-exome or whole-genome sequencing. Recently, we designed a customized gene panel for targeted sequencing of major solid cancers. In this study, we aimed to validate its performance. The cancer panel targets 95 cancer-related genes. In terms of the limit of detection, more than 86% of target mutations with a mutant allele frequency (MAF) 3% MAF can be detected. When we applied this system for the analysis of Acrometrix Oncology Hotspot Control DNA, which contains more than 500 COSMIC mutations across 53 genes, 99% of the expected mutations were robustly detected. We also confirmed the high reproducibility of the detection of mutations in multiple independent analyses. When we explored copy number alterations (CNAs), the expected CNAs were successfully detected, and this result was confirmed by target-specific genomic quantitative polymerase chain reaction. Taken together, these results support the reliability and accuracy of our cancer panel in detecting mutations. This panel could be useful for key mutation profiling research in solid tumors and clinical translation.

Relationship between Mucoid Degeneration of the Anterior Cruciate Ligament and Posterior Tibial Slope in Patients with Total Knee Arthroplasty

PURPOSE: The purpose was to analyze the relationship between posterior tibial slope (PTS) and mucoid degeneration of the anterior cruciate ligament (ACL) in patients with total knee arthroplasty. MATERIALS AND METHODS: Four hundred and twenty-four patients (24 males and 400 females; 636 knees) who received total knee arthroplasty for osteoarthritis were included. Their mean age was 68.9 years (range, 48 to 88 years). The patients were classified into three groups according to the status of ACL; normal ACL group (group I), mucoid degeneration of ACL group (group II) and ruptured or absent ACL group (group III). Plain lateral radiographs were used to measure the PTS and the values were compared among groups. RESULTS: There were no significant differences with regard to gender, age and left-to-right side ratio among groups (p>0.05). The mean PTS was 9.9degrees (range, 0.6degrees to 20.1degrees) in group I (161 knees), 10.8degrees (range, 0.2degrees to 21.8degrees) in group II (342 knees) and 12.3degrees (range, 2degrees to 22.2degrees) in group III (133 knees), which showed significant differences (p<0.001). CONCLUSIONS: The patients with mucoid degeneration of the ACL and those with ruptured or absent ACL had greater PTS than those with normal ACL. These findings suggest that an increased PTS may be one of the causative factors for mucoid degeneration of the ACL.

Clinical implications of copy number variations in autoimmune disorders

Human genetic variation is represented by the genetic differences both within and among populations, and most genetic variants do not cause overt diseases but contribute to disease susceptibility and influence drug response. During the last century, various genetic variants, such as copy number variations (CNVs), have been associated with diverse human disorders. Here, we review studies on the associations between CNVs and autoimmune diseases to gain some insight. First, some CNV loci are commonly implicated in various autoimmune diseases, such as Fcgamma receptors in patients with systemic lupus erythemoatosus or idiopathic thrombocytopenic purpura and beta-defensin genes in patients with psoriasis or Crohn's disease. This means that when a CNV locus is associated with a particular autoimmune disease, we should examine its potential associations with other diseases. Second, interpopulation or interethnic differences in the effects of CNVs on phenotypes exist, including disease susceptibility, and evidence suggests that CNVs are important to understand susceptibility to and pathogenesis of autoimmune diseases. However, many findings need to be replicated in independent populations and different ethnic groups. The validity and reliability of detecting CNVs will improve quickly as genotyping technology advances, which will support the required replication.

Osteoid Osteoma in Wrist: A Case Report / 대한골관절종양학회지

Osteoid osteoma can occur in all parts of the skeletal system. More than half occur in lower extremity and rare in wrist.Clinically pain is almost the only symptom worse at night and which is characterized by a rapid improvement by NSAID. We report the cases of osteoid osteoma which shows the characteristic symptoms and got a good results with appropriate imaging work up and surgical treatment.

Silencing of KIF14 interferes with cell cycle progression and cytokinesis by blocking the p27(Kip1) ubiquitination pathway in hepatocellular carcinoma

Although it has been suggested that kinesin family member 14 (KIF14) has oncogenic potential in various cancers, including hepatocellular carcinoma (HCC), the molecular mechanism of this potential remains unknown. We aimed to elucidate the role of KIF14 in hepatocarcinogenesis by knocking down KIF14 in HCC cells that overexpressed KIF14. After KIF14 knockdown, changes in tumor cell growth, cell cycle and cytokinesis were examined. We also examined cell cycle regulatory molecules and upstream Skp1/Cul1/F-box (SCF) complex molecules. Knockdown of KIF14 resulted in suppression of cell proliferation and failure of cytokinesis, whereas KIF14 overexpression increased cell proliferation. In KIF14-silenced cells, the levels of cyclins E1, D1 and B1 were profoundly decreased compared with control cells. Of the cyclin-dependent kinase inhibitors, the p27Kip1 protein level specifically increased after KIF14 knockdown. The increase in p27Kip1 was not due to elevation of its mRNA level, but was due to inhibition of the proteasome-dependent degradation pathway. To explore the pathway upstream of this event, we measured the levels of SCF complex molecules, including Skp1, Skp2, Cul1, Roc1 and Cks1. The levels of Skp2 and its cofactor Cks1 decreased in the KIF14 knockdown cells where p27Kip1 accumulated. Overexpression of Skp2 in the KIF14 knockdown cells attenuated the failure of cytokinesis. On the basis of these results, we postulate that KIF14 knockdown downregulates the expression of Skp2 and Cks1, which target p27Kip1 for degradation by the 26S proteasome, leading to accumulation of p27Kip1. The downregulation of Skp2 and Cks1 also resulted in cytokinesis failure, which may inhibit tumor growth. To the best of our knowledge, this is the first report that has identified the molecular target and oncogenic effect of KIF14 in HCC.