WWC proteins mediate LATS1/2 activation by Hippo kinases and imply a tumor suppression strategy.

YAP and TAZ (YAP/TAZ), two major effectors of the Hippo signaling pathway, are frequently activated in human cancers. The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. However, it is unclear how LATS1/2 are precisely regulated by upstream factors such as Hippo kinases MST1/2. Here, we show that WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. Hence, WWC1/2/3 play an organizer role in a signaling module that mediates LATS1/2 activation by MST1/2. Moreover, we have defined a minimum protein interaction interface on WWC1/2/3 that is sufficient to activate LATS1/2 in a robust and specific manner. The corresponding minigene, dubbed as SuperHippo, can effectively suppress tumorigenesis in multiple tumor models. Our study has uncovered a molecular mechanism underlying LATS1/2 regulation and provides a strategy for treating diverse malignancies related to Hippo pathway dysregulation.

Two Hippo signaling modules orchestrate liver size and tumorigenesis.

The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2-SAV1-WWC1-3 (HPO1) and MAP4K1-7-NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC). On the contrary, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality. Interestingly, HPO1 has a predominant role in regulating organ size. HPO1 inactivation causes a homogenous YAP/TAZ activation and cell proliferation across the whole liver, resulting in a proportional and rapid increase in liver size. Thus, this study has reconstructed the order of the Hippo signaling network and suggests that LATS1/2 and YAP/TAZ activities are finetuned by HPO1 and HPO2 modules to cause different cell fates, organ size changes, and tumorigenesis trajectories.

Gasless Single-Incision Endoscopic Surgery via Subclavicular Approach for Lateral Neck Dissection in Patients with Papillary Thyroid Cancer.

BACKGROUND: The technical difficulties and trauma of remote access methods in endoscopic surgery (ES) for lateral neck dissection (LND) can be daunting for most patients with papillary thyroid cancer (PTC) and surgeons. The purpose of study was to introduce gasless single-incision ES via a subclavicular approach (ESSA) and to explore its safety and efficacy for LND. METHODS: Between January 2022 and February 2023, we retrospectively reviewed 17 patients with PTC who underwent ESSA for LND. In addition, 22 patients who received video-assisted ES (VAES) and 48 patients who underwent open surgery (OP) for LND during the same period were included. Clinicopathological characteristics, complications, and efficacy of the lymph node yield (LNY) were compared between the ESSA and the other two groups (VAES and OP). RESULTS: The LNY from central and lateral neck dissection by ESSA was comparable to that by VAES (9.2 ± 8.1 vs. 9.5 ± 4.2, P = 0.986, and 33.5 ± 11.6 vs. 30.6 ± 9.2, P = 0.382, respectively) and OP (9.2 ± 8.1 vs. 11.0 ± 5.4, P = 0.420, and 33.5 ± 11.6 vs. 31.5 ± 7.9, P = 0.383, respectively). Swallowing impairment scores at 1 and 3 months were significantly lower after ESSA than those after VAES (1.8 ± 1.0 vs. 3.0 ± 1.2, P = 0.003, and 0.9 ± 0.8 vs. 1.7 ± 0.8, P = 0.006, respectively). The cosmetic satisfaction rate 1 month after surgery was significantly higher in the ESSA group than that in the VAES group (100 vs. 31.8%, P < 0.001). CONCLUSIONS: ESSA is a safe and minimally invasive procedure that provides a scarless cervical appearance and has good efficacy for LND. Therefore, ESSA may be a feasible choice for selected patients with N1b PTC with cervical cosmetic needs.

Characterization of myeloid signature genes for predicting prognosis and immune landscape in Ewing sarcoma.

Myeloid cells as a highly heterogeneous subpopulation of the tumor microenvironment (TME) are intimately associated with tumor development. Ewing sarcoma (EWS) is characterized by abundant myeloid cell infiltration in the TME. However, the correlation between myeloid signature genes (MSGs) and the prognosis of EWS patients was unclear. In this research, we synthetically characterized the expression of MSGs in a training cohort and classified EWS patients into two subtypes. Immune cell infiltration analysis revealed that MSGs subtypes correlated closely with different immune statuses. Furthermore, a three-gene prognostic model (CTSD, SIRPA, and FN1) was constructed by univariate, LASSO, and multivariate Cox analysis, and it showed excellent prognostic accuracy in EWS patients. We also developed a nomogram for better predicting the long-term survival of EWS. Functional enrichment analysis showed immune-related pathways were distinctly different in the high- and low-risk groups. Further analysis revealed that patients in the high-risk group were tightly associated with an immunosuppressive microenvironment. Finally, we validated the expression of these candidate genes by Western blot (WB), qPCR, and immunohistochemistry (IHC) analysis. To sum up, our study identified that the MSGs model was strongly linked to prognostic prediction and immune infiltration in EWS patients, providing novel insights into the clinical treatment and management of EWS patients.

Development and experimental validation of a folate metabolism-related gene signature to predict the prognosis and immunotherapeutic sensitivity in bladder cancer.

Folate metabolism is critical for the maintenance of genomic stability due to its regulatory ability to methylation, nucleotide metabolism, and reduction capabilities in cancer cells. However, the prognostic value of folate metabolism-related genes has not been clarified, especially in bladder cancer (BLCA). 91 folate metabolism-related genes were retrieved from the public database. TCGA-BLCA cohort, obtained from the Cancer Genome Atlas, was selected for training, while GSE13507, GSE31684, and GSE32894, downloaded from the Gene Expression Omnibus, and 35 BLCA samples collected from the local hospital were used for external validation. Through genomic difference detection, protein-protein interaction network analysis, LASSO regression, and Cox regression, a three-gene signature, including ATIC, INS, and MTHFD1L, was constructed. The signature was a reliable prognosis predictor across multiple independent cohorts (pooled hazard ratio = 2.79, 95% confidence interval = 1.79-4.33). The signature was associated with the BLCA malignant degree, which was validated in the local clinical samples (P < 0.01) and multiple cell lines (all P < 0.05). Additionally, the TIDE algorithm, GSE111636 cohort, and IMvigor210 cohort indicated that the signature was a promising tool to evaluate the immunotherapeutic response. Collectively, a folate metabolism-related gene signature was constructed to predict the prognosis and immunotherapeutic sensitivity in BLCA, which was verified in multiple large-scale cohorts, clinical samples, and cellular experiments, providing novel insights into the biological mechanisms.

Identification of key biomarkers related to epithelial-mesenchymal transition and immune infiltration in ameloblastoma using integrated bioinformatics analysis.

OBJECTIVE: This study aimed to elucidate the underlying mechanisms of ameloblastoma (AM) through integrated bioinformatics analysis. METHODS: We downloaded two microarrays of AMs from the GEO database and identified differentially expressed genes (DEGs) by integrated bioinformatics analysis. The enrichment analysis of DEGs was conducted to characterize GO and KEGG pathways. Protein-protein interaction (PPI) network and hub genes were screened via STRING and Cytoscape. CIBERSORT algorithm was utilized to analyze immune infiltration in AMs. We also verified the diagnostic and therapeutic value of hub genes. RESULTS: Overall, 776 DEGs were identified in AMs through bioinformatics analysis. The function enrichment analysis shed light on pathways involved in AMs. Subsequently, we screened six hub genes via PPI network. Furthermore, we evaluated immune infiltration in AMs and found that macrophages may be participating in the progression of AMs. The upregulated expression of FN1 was related to the macrophages M2 polarization. Finally, ROC analysis indicated that six hub genes had high diagnostic value for AMs and 11 drugs interacted with upregulated hub genes were identified by screening the DGIdb database. CONCLUSION: This study revealed the underlying mechanisms of pathogenesis and biological behavior of AMs and provided candidate targets for the diagnosis and treatment of AMs.

TOR1AIP1-Associated Nuclear Envelopathies.

Human TOR1AIP1 encodes LAP1, a nuclear envelope protein expressed in most human tissues, which has been linked to various biological processes and human diseases. The clinical spectrum of diseases related to mutations in TOR1AIP1 is broad, including muscular dystrophy, congenital myasthenic syndrome, cardiomyopathy, and multisystemic disease with or without progeroid features. Although rare, these recessively inherited disorders often lead to early death or considerable functional impairment. Developing a better understanding of the roles of LAP1 and mutant TOR1AIP1-associated phenotypes is paramount to allow therapeutic development. To facilitate further studies, this review provides an overview of the known interactions of LAP1 and summarizes the evidence for the function of this protein in human health. We then review the mutations in the TOR1AIP1 gene and the clinical and pathological characteristics of subjects with these mutations. Lastly, we discuss challenges to be addressed in the future.

Customized three dimensional printed prosthesis as a novel intercalary reconstruction for resection of extremity bone tumours: a retrospective cohort study.

AIMS: The 3D-printed prosthesis (3DP) is a novel treatment for massive bone defect reconstruction after tumor resection. This study was aiming to explore the clinical efficacy of customized 3DP for intercalary reconstruction by comparing the clinical outcomes after implanting customized 3DP or conventional allograft in limb salvage surgery. METHODS: A total of 28 patients with extremity bone tumors who underwent customized 3DP or conventional allograft reconstruction between 2011 and 2018 at our institution were analyzed retrospectively. Among them, 14 cases received customized 3DP reconstruction (3DP group), and 14 cases received conventional allograft reconstruction (control group). Demographics, surgical outcomes, radiographical assessments, limb functions, and post-operative complications between these two groups were collected to evaluate clinical outcomes. RESULTS: No significant difference was observed in the demographics, mean intra-operative blood loss, MOSI scores, and MSTS scores between the two groups. Patients in 3DP group had a shorter operative time (157.9 vs 199.6 min, p = 0.03) and lesser number of fluoroscopy (4.1 vs 8.1, p < 0.001) compared to control group. The mean time to osseointegration at bone-implant interfaces in 3DP group was significantly earlier than that in control group (6.1 vs 12.2 months, p < 0.001). Moreover, the 3DP group had a significantly lower post-operative complication rate than the control group (7% vs 50%, p = 0.03). CONCLUSIONS: The customized 3DP might provide a promising strategy for intercalary reconstruction in limb salvage surgery with more precise reconstruction, higher surgical efficiency, and comparable satisfactory clinical outcomes.

Lonidamine potentiates the oncolytic efficiency of M1 virus independent of hexokinase 2 but via inhibition of antiviral immunity.

BACKGROUND: Viruses are obligate parasites that depend on host cells to provide the energy and molecular precursors necessary for successful infection. The main component of virus-induced metabolic reprogramming is the activation of glycolysis, which provides biomolecular resources for viral replication. However, little is known about the crosstalk between oncolytic viruses and host glycolytic processes. METHODS: A MTT assay was used to detect M1 virus-induced cell killing. Flow cytometry was used to monitor infection of M1 virus expressing the GFP reporter gene. qPCR and western blotting were used to detect gene expression. RNA sequencing was performed to evaluate gene expression under different drug treatments. Scanning electron microscopy was performed to visualize the endoplasmic reticulum (ER). Caspase activity was detected. Last, a mouse xenograft model was established to evaluate the antitumor effect in vivo. Most data were analyzed with a two-tailed Student's t test or one-way ANOVA with Dunnett's test for pairwise comparisons. Tumor volumes were analyzed by repeated measures of ANOVA. The Wilcoxon signed-rank test was used to compare nonnormally distributed data. RESULTS: Here, we showed that the glucose analog 2-deoxy-D-glucose (2-DG) inhibited infection by M1 virus, which we identified as a novel type of oncolytic virus, and decreased its oncolytic effect, indicating the dependence of M1 replication on glycolysis. In contrast, lonidamine, a reported hexokinase 2 (HK2) inhibitor, enhanced the infection and oncolytic effect of M1 virus independent of HK2. Further transcriptomic analysis revealed that downregulation of the antiviral immune response contributes to the lonidamine-mediated potentiation of the infection and oncolytic effect of M1 virus, and that MYC is the key factor in the pool of antiviral immune response factors inhibited by lonidamine. Moreover, lonidamine potentiated the irreversible ER stress-mediated apoptosis induced by M1 virus. Enhancement of M1's oncolytic effect by lonidamine was also identified in vivo. CONCLUSIONS: This research demonstrated the dependence of M1 virus on glycolysis and identified a candidate synergist for M1 virotherapy.

The circRNA circP4HB promotes NSCLC aggressiveness and metastasis by sponging miR-133a-5p.

BACKGROUND: Non-small cell lung carcinoma (NSCLC) continues to top the list of cancer mortalities worldwide. The role of circular RNAs (circRNAs) in tumorigenesis has been increasingly appreciated, although it is relatively unexplored in NSCLC. Herein, we report on the role of circP4HB in NSCLC. METHODS: First, we evaluated circP4HB levels in patient-derived NSCLC tissue versus paired healthy samples. Next, we conducted experiments in vitro in NSCLC cell-lines and in vivo in a murine xenograft NSCLC model to assess the impact of circP4HB on epithelial-mesenchymal transition (EMT) in vitro and metastasis in vivo. The downstream impact of circP4HB on the microRNA miR-133a-5p, and its target the EMT marker vimentin, were also evaluated. RESULTS: NSCLC tumor specimens exhibited higher circP4HB levels in comparison to paired healthy lung samples and was associated with metastatic disease and poorer survival. circP4HB promoted EMT and vimentin expression in vitro and xenograft metastasis in vivo through sequestration of miR-133a-5p. CONCLUSION: circP4HB enhances EMT and metastatic disease through miR-133a-5p sequestration, leading to upregulation of vimentin. Therefore, these findings advocate targeting the circP4HB/miR-133a-5p/vimentin axis as a potential therapeutic option for NSCLC patients.

Acid sphingomyelinase mediates the noise-induced liver disorder in mice.

Noise-induced structural and functional disorder of the liver has been realized, but the underlying mechanism remains to be characterized, which has limited the introduction of precautious measures. Over-activation of acid sphingomyelinase (ASM)/ceramide (Cer) pathway takes centre stage in hepatocyte injury entailed by various stimulus. We aimed to investigate whether it mediated the noise elicited liver disorder on infrastructure, lipid metabolism, apoptosis, and oxidative stress. Mice were exposed to broad band noise (20-20k Hz, 90-110 dB) for 1, 3, 5 or 7 days by 3 hr/d. Doxepin hydrochloride (DOX), an ASM inhibitor was given by 5 mg/kg/d gavage. We showed that 5 or 7 days intense, broad band noise exposure caused significant infrastructure derangement and lipid droplets storage in hepatocytes. The content of cholesterol, free fatty acids or triglyceride was increased significantly in liver tissue upon noise stimulation. Moreover, the noise promoted apoptosis and superoxide generation in hepatocytes significantly, enhancing activity of aspartate aminotransferase (AST) or alanine amino transferase (ALT) in serum. Acid sphingomyelinase activity and Cer generation in liver tissue were elevated by noise exposure, which was normalized with DOX administrated. Accordingly, DOX alleviated steatosis, apoptosis, oxidative stress and enzymatic change in hepatocytes or serum of noise exposed mice substantially. In summary, our results suggest the ASM/Cer pathway contributes to the broad band noise elicited liver damage in mice.

MTHFD2 Overexpression Predicts Poor Prognosis in Renal Cell Carcinoma and is Associated with Cell Proliferation and Vimentin-Modulated Migration and Invasion.

BACKGROUND/AIMS: To investigate the role of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in the clinical prognosis and cell biology of renal cell carcinoma (RCC). METHODS: A total of 137 RCC tissues were evaluated by immunohistochemistry. The relationship between MTHFD2 overexpression and clinical parameters and vimentin expression was assessed. Kaplan-Meier curves and the log-rank test were applied for survival analysis according to MTHFD2 and vimentin expression in RCC tissues. The expression of MTHFD2 mRNA and protein was examined by quantitative reverse transcription PCR and western blotting, respectively. To determine further the biological activity of MTHFD2 in RCC, 786-O cells were transfected with short hairpin RNA specifically targeting MTHFD2 (shMTHFD2) with or without tumor necrosis factor (TNF)-α stimulation. Cell proliferation, cell migration and invasion and drug sensitivity were subsequently assessed using Cell Counting Kit-8, wound healing, and Transwell assays. RESULTS: Immunohistochemical analysis demonstrated that both MTHFD2 and vimentin overexpression was positively associated with clinical staging, pathological grade, and poor overall survival (all P < 0.05). MTHFD2 expression was closely correlated with vimentin overexpression in RCC (r = 0.402, P < 0.001). After knocking down MTHFD2 expression in 786-O cells, decreased cell proliferation, migration, and invasion were observed and accompanied by the reduced expression of vimentin. The effects of MTHFD2 down-regulation could be partially restrained by TNF-α treatment. Vimentin expression and cell migration and invasion, but not cell proliferation, were reversed by TNF-α stimulation. Furthermore, treatment of 786-O cells with shMTHFD2 increased their sensitivity to chemotherapy drugs. CONCLUSION: The current results demonstrated that MTHFD2 was overexpressed in RCC and associated with poor clinical characteristics, vimentin expression, and cellular features connected to malignant disease, thus, implicating MTHFD2 as a potential target for RCC therapy.

Research on high-resolution imaging technology based on light field manipulation for a lenslet-based plenoptic camera.

In this paper, an aberration correction method for an extended target is proposed to solve the problem of the lenslet-based plenoptic camera not imaging clearly under the influence of aberrations. We propose a light field manipulation method to improve performance of the light field imaging system. The principle of this method is that the sub-aperture images extracted from the raw light field image are offset when the light field imaging system is affected by aberrations, and the symmetrical arrangement of the sub-aperture image array is destroyed. By repairing the symmetrical arrangement of the sub-aperture image array, the influence of phase aberrations on the imaging system can be eliminated, and the resolution of the plenoptic camera can be improved. We use an image correlation algorithm to process the sub-aperture images of the plenoptic camera, calculate and compensate each sub-aperture image's displacement caused by aberrations, and restore the symmetrical arrangement of the sub-aperture image array; then, a corrected high-resolution refocused image can be generated. In particular, this method uses only the raw light field information obtained by the plenoptic camera in a single exposure, without adding other hardware devices. Furthermore, it takes the extended target itself as the reference image, so the ideal position need not be calibrated in advance. Also, the parallax information of the sub-aperture images is retained, and the method is simple and easy to use. Numerical simulation and experimental results show that the technology proposed in this paper can work well for high-resolution imaging of a plenoptic camera with phase aberrations. This method can be potentially applied to analyze lens aberration, media-induced image distortion such as water turbulence in underwater imaging, and atmospheric turbulence in remote imaging. It may have important application prospects in the fields of astronomical object detection, remote sensing, etc.

Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus-related hepatocellular carcinoma metastasis through the upregulation of ADAM9.

Hepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, baseline miR-126 expression levels in hepatitis B virus-related hepatocellular carcinoma patients who did not undergo pre-operational treatment remains unknown since hepatitis B virus infection and pre-operational transcatheter arterial chemoembolization were shown to upregulate miR-126 expression. Here, we demonstrated that miR-126 is generally downregulated in a homogeneous population of pre-operational treatment-naïve hepatitis B virus-related hepatocellular carcinoma patients (84.0%, 84/100), and its expression is significantly associated with pre-operational alpha-fetoprotein levels ( p < 0.05), microvascular invasion ( p < 0.05), tumor metastasis ( p < 0.05), as well as early recurrence (12 months after surgery; p < 0.01). Furthermore, the results of our study revealed that miR-126 is negatively correlated with ADAM9 expression in hepatitis B virus-related hepatocellular carcinoma patients. Overexpression of miR-126 was shown to attenuate ADAM9 expression in hepatocellular carcinoma cells, which subsequently inhibits cell migration and invasion in vitro. In addition, Cox proportional hazards regression model analysis showed that ADAM9 levels, tumor number, microvascular invasion, and tumor metastasis rate represent independent prognostic factors for shorter recurrence-free survival. In conclusion, we demonstrated that the loss of tumor suppressor miR-126 in hepatitis B virus-related hepatocellular carcinoma cells contributes to the development of metastases through the upregulated expression of its target gene, ADAM9. MiR-126-ADAM9 pathway-based therapeutic targeting may represent a novel approach for the inhibition of hepatitis B virus-related hepatocellular carcinoma metastases.

TPX2 Level Correlates with Hepatocellular Carcinoma Cell Proliferation, Apoptosis, and EMT.

BACKGROUND: Targeting protein for Xklp2 (TPX2) is a microtubule-associated protein involved in targeting the motor protein Xklp2 to microtubules. TPX2 overexpression plays a key role in the progression of human cancers. But the underlying mechanism remains unclear. AIMS: This study aimed to investigate the effects and mechanisms of TPX2 on the cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC). METHODS: The tissue TPX2 mRNA and protein were assessed by quantitative reverse transcriptase PCR and immunoblot. Cell proliferation, cell cycle, apoptosis, and invasion were determined by CCK-8, FACS, TdT-UTP nick end-labeling, and transwell assays. Immunoblotting was performed to detect the expression of target proteins. RESULTS: TPX2 was highly expressed in tumor tissues compared with non-tumoral tissues, and TPX2 overexpression was positively correlated with poor prognosis. Knockdown TPX2 effectively reduced cell growth, G2/M arrest, induced apoptosis and cell death, and inhibited EMT. Mechanistically, in the TPX2-siRNA-treated groups, cell-cycle-related proteins cyclin A1, cyclin B1, cyclin E1, and cdk4 were up-regulated, while cyclin D1, cdk2, and p21 proteins were down-regulated. Cell-apoptosis-related proteins Bax, p53, caspase-3, and caspase-8 levels were increased. EMT-related proteins E-cadherin was up-regulated, while N-cadherin, ß-catenin, MMP-9, MMP-2, and Slug were down-regulated. We also found that knockdown TPX2 in HCC cell lines caused a significant decrease in the level of p-Akt and p-ERK which are important signaling pathways in tumor formation. CONCLUSIONS: TPX2 expression is associated with proliferation, apoptosis, and EMT in hepatocellular carcinoma cell and patients.

[The preliminary study on the function of methylenetetrahydrofolate dehydrogenase 2 in hepatocellular carcinoma].

OBJECTIVE: To investigate the expression of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in hepatocellular carcinoma (HCC) tissues and its correlation with clinical parameters. METHOD: Fluorogenic quantitative-polymerase chain reaction (FQ-PCR) was used to measure the MTHFD2 mRNA expression. The MTHFD2 protein expression was detected by immunohistochemical staining in cancerous tissues and adjacent noncancerous counterparts. The relationship of MTHFD2 expression, clinicopathological parameters and the prognosis of hepatocellular carcinoma was subsequently analysed. RESULTS: The MTHFD2 mRNA expression in cancerous tissues was higher than that in adjacent noncancerous counterparts (31/47) (P<0.05). The positive rate of MTHFD2 protein in cancerous tissues was significantly higher than that in adjacent noncancerous counterparts (69.5% vs. 33.9%) (P<0.05). MTHFD2 overexpression was found to correlate with clinical pathological parameters such as tumor metastasis, recurrence and poor prognosis (P<0.05). The patients with overexpressed MTHFD2 had shorter tumor-free survival time. CONCLUSIONS: Overexpression of MTHFD2 in HCC may be a risk factor of tumor metastasis and recurrence. MTHFD2 could be a new biomarker for prognosis of HCC.

[Expression of TPX2 in hepatocellular carcinoma and its clinical significance].

OBJECTIVE: To explore the expression of TPX2 and its significance in hepatocellular carcinoma (HCC) tissue and examine the relationship between TPX2 and clinicopathological characteristics of HCC. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining were used to compare the expression of TPX2 in tumor and adjacent non-tumoral tissues. RESULTS: The TPX2 mRNA expression was higher in tumor tissues than that in non-tumoral counterparts (30/50) (P < 0.05). The positive rate of TPX2 protein in tumor tissues was significantly higher than that in non-tumoral counterparts (56.0% vs 16.0%) (P < 0.05). The expression of TPX2 mRNA and protein were correlated with metastasis, recurrence and time of recurrence after curative resection (P < 0.05). CONCLUSION: An over-expression of TPX2 may be risk factor of metastasis and recurrence after curative resection so that it is a potential biomarker for early diagnosis and prognosis of HCC.

[Expression of novel metastasis-promoting gene 1 and its clinical significance in hepatocellular carcinoma].

OBJECTIVE: To explore the expression of NVM-1(novel metastasis-promoting gene 1) in hepatocellular carcinoma (HCC) tissue and examine its clinical significance. METHODS: The expression of NVM-1 in 92 cases of HCC tumor tissues and non-tumor tissues was detected by immunohistochemical staining with SP (streptavidin-perosidase). And its clinical significance was evaluated. RESULTS: The staining of NVM-1 was predominantly located in the nucleus of HCC tumor tissue. The positive rate of NVM-1 was 52.2% in all detected cancers and it was higher than that in control non-tumor tissues (28.3%) and benign hepatic lesions (0) . A significant difference of positive rates existed between tumor and non-tumor tissues (P < 0.05). The expression of NVM-1 in HCC was not correlated with hepatic B virus (HBV), size, amount or cirrhosis, etc. However, it was correlated with TNM (P = 0.016), BCLC stage (P = 0.015), poor differentiation (P = 0.000), intrahepatic metastasis (P = 0.002), portal vein tumor thrombus (P = 0.023) and recurrence (P = 0.001). By Kaplan-Meier analysis, the median tumor-free survival time was 5 months in positive expression group and it was significantly shorter than 13 months in negative expression group (P = 0.001). CONCLUSION: There is probably a close relation between recurrence and metastasis and the expression of NVM-1 in HCC.