ABSTRACT
BACKGROUND: The nuclear division cycle 80 (NDC80) complex assures proper chromosome segregation during the cell cycle progression. SPC25 is a crucial component of NDC80, and its role in hepatocellular carcinoma (HCC) has been explored recently. This study characterized the differential expression of SPC25 in HCC patients of different races and HBV infection status. METHODS: Expression patterns of SPC25 were evaluated in TCGA and Chinese HCC patients. Kaplan-Meier analysis was applied to examine the predictive value of SPC25. In vitro and in vivo functional assays were conducted to explore the role of SPC25 in HCC. Bioinformatics methods were applied to investigate the regulatory mechanisms of SPC25. FINDINGS: The mRNA levels of SPC25 were up-regulated in HCC. SPC25 has a significantly higher transcriptional level in Asian patients than Caucasian patients. SPC25 promoted HCC cell proliferation in vitro and tumor growth in vivo by accelerating the cell cycle. We identified transcription factors, miRNAs, and immune cells that may interact with SPC25. INTERPRETATION: The findings suggest that increased expression of SPC25 is associated with poor prognosis of HCC and enhances the proliferative capacity of HCC cells. SPC25 could serve as a valuable prognostic marker and a novel treatment target for HCC.
Subject(s)
Carcinoma, Hepatocellular/genetics , Cell Proliferation/genetics , Liver Neoplasms/genetics , Microtubule-Associated Proteins/genetics , RNA, Messenger/metabolism , Animals , Asian People , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/mortality , Cell Line, Tumor , Cytoskeletal Proteins , Databases, Genetic , Female , Hep G2 Cells , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/genetics , Humans , In Vitro Techniques , Liver Neoplasms/complications , Liver Neoplasms/mortality , Male , Mice , Mice, Nude , Middle Aged , Neoplasm Transplantation , Survival Rate , Up-Regulation , White PeopleABSTRACT
OBJECTIVE: To provide more evidence sources to the standard treatment for patients with advanced hepatocellular carcinoma, the writer analyze patients' time to progression (TTP) and overall survival (OS) after patients receiving transcatheter arterial chemoembolization (TACE) combined with sorafenib as a treatment of advanced hepatocellular carcinoma (HCC); observe the healing effect embolization combined with anti-angiogenic treatment for advanced hepatocellular carcinoma; and also analyze treatment of security. METHODS: There are 36 patients, 33 male and 3 female had been Pathologically or clinical diagnosis. After receiving Transcatheter Arterial Chemoembolization (TACE) therapy, in the following 3 to 7 days, this group of patients continuously take sorafenib (brand name: Nexavar) (per tablet 200 mg), 2 tablets each time, 2 times a day. Every 4 to 8 weeks is called as one period of treatment. Referring to RECIST Evaluation, the writers mainly observe patients' tumor progression (TTP) and overall survival (OS), record adverse events. Using life table method to analyze survival rate, using Kaplan-Meier method to analyze all the survival curves. RESULTS: Till March, 2010, 14 of 36 evaluable patients died and 22 survive; the median time to tumor progression (mTTP) to 8.62 months (95%CI: 6.51-10.24 months); the median survival time (mOS) of 12.41 months (95%CI: 9.57-14.80 months). The overall survival rate to observation period is 61.1%; 36 patients had been studied, 22 survive. Among the survivals, there is no CR cases, and 1 case PR, 15 patients SD, 6 patients PD; disease control rate (DCR) (CR + PR + SD) is 44.4%. The side effects of taking Sorafenib mainly are hand-foot skin reaction, diarrhea, fatigue and loss of appetite. These side effects can be markedly eased after symptomatic treatment. CONCLUSION: Combined with sorafenib treatment may give patients with advanced hepatocellular carcinoma a longer longevity and keep the disease in a steady state. This therapy can be added into the treatments to patients with advanced hepatocellular carcinoma. The side effects of taking Sorafenib (Nexavar) could be stand.