Expression and clinical significance of Bmi-1 in gastric carcinoma

AIM: To investigate the relationship between expression of Bmi-1 (B cell-specific MLV integration site-1) in gastric cancer and its clinicopathologic significance.METHODS: 146 surgical patients with gastric carcinoma were followed up at least 2 years.Expression of Bmi-1 protein was examined by immunohistochemistry in their archival paraffin embedded tissue specimens.RESULTS: The intensive positive rate of Bmi-1 expression in gastric cancer was 67.8% (99/146).Expression of Bmi-1 was highly correlated with tumor size,clinical stage,lymph node metastasis and T classification (P<0.05),but not with sex,age,tumor differentiation,etc.(P>0.05).The survival rate in the patients with Bmi-1 expression was much lower than that in those patients without Bmi-1 expression (P<0.01).Multivariate analysis indicated that Bmi-1 expression,T classification,lymph node metastasis,distant metastasis,tumor size and postoperative chemotherapy were all significantly prognostic factors of gastric carcinoma.CONCLUSION: Overexpression of Bmi-1 in patients with gastric carcinoma enhances the possibility of invasion and metastasis,implying a poor prognosis.Bmi-1 may serve as fairly a good prognostic factor to indicate biologic behavior and prognosis in gastric carcinoma.     

Expression and prognostic significance of SLP-2 in gastric cancer

AIM: To investigate the expression of the red cell membrane integration protein SLP-2 (stomatin-like protein 2) in gastric cancer tissues and to analyze its correlation with clinicopathological manifestations and prognosis. METHODS: One hundred and ninety gastric cancer tissue samples with detailed clinical information were collected from the Department of Pathology, Sun Yat-sen University Cancer Center. The protein expression of SLP-2 in ganstric cancer was detected by the method of immunohistochemistry. The relationships between SLP-2 expression and the clinicopathological manifestations were evaluated. RESULTS: The positive rate of SLP-2 in gastric cancer tissue was 63.2% (120/190). SLP-2 expression was relevant to infiltration depth, TNM stage and lymph node metastasis (P<0.05). However, no statistical difference was observed in the SLP-2 expression associated with sex, age, differentiation, tumor size and distant metastases. Kaplan-Meier survival curves revealed that increased expression of SLP-2 was associated with poor prognosis in gastric adenocarcinoma patients (P<0.01). Based on the univariate analysis, 7 factors were found to have statistical significance of associations with overall survival, including SLP-2 expression, lymph node metastasis, histological grade, tumor size, invasive depth, distant metastases and the 7th edition of the UICC TNM classification. Only the tumor size and the 7th edition of the UICC TNM classification were independent prognostic factors for overall survival in the multivariate analysis. CONCLUSION: SLP-2 is highly expressed in gastric adenocarcinoma tissues and may play an important role in tumor progression and metastasis. Although SLP-2 is not an independent prognostic factor, it may influence the prognosis of gastric cancer. Increased expression of SLP-2 can be used for predicting unfavorable prognosis in gastric adenocarcinoma patients.     

Expression and clinical significance of Bmi-1 in colorectal cancer

AIM:This study was to investigate the expression and significance of Bmi-1 in colorectal carcinoma (CRC), and to explore the effect of Bmi-1 on Ki67 expression in human CRC.METHODS:The samples from sixty CRC, thirty adenomas and twenty normal colorectal mucosal tissues were used in this study.The expression of Bmi-1 protein was detected by immunohistochemistry.The clinicopathological features and survival rate of patients were also analyzed.RESULTS:The overexpression of Bmi-1 was respectively 25.0％, 6.7％and 0% in CRC and adenomas as well as normal colorectal mucosal tissues.The results showed that the expression of Bim-1 was significantly higher in CRC, compared with that in adenomas and normal colorectal mucosal tissues (P<0.05).The overexpression of Bmi-1 protein in CRC was obviously associated with distant metastasis and TNM stage (P<0.05), but not with gender, age, tumor size, tumor site, histological type, differentiation degree and lymph node metastasis (P>0.05).Kaplan-Meier survival analysis showed that the overexpression of Bmi-1 reduced significantly survival of CRC patients (P<0.05).No statistical relation between expression of Bmi-1 and Ki67 in CRC was observed.CONCLUSION:The overexpression of Bmi-1 protein is significantly correlated with tumorigenesis, metastasis and prognosis of CRC.Bmi-1 might be regarded as a parameter in evaluating prognosis of CRC.     

Relationship between expression of COX-2 and clinicopathological features in esophageal carcinoma

AIM:To examine COX-2 expression in esophageal carcinoma, and to study relationships between COX-2 expression and clinicopathological features and prognosis of esophageal carcinoma patients. METHODS:89 paraffin - embedded tissue samples from patients with esophageal carcinoma were collected, its clinicopathological features such as tumour differentiation, depth of invasion, length and site of the tumor, regional lymph node metastases, distant metastasis were recorded. Survival time of 81 cases were also recorded. By SP immunohistochemistry method, the expression of COX-2 in tumor samples was examined. RESULTS:COX-2 expression in esophageal carcinoma was markedly higher than that in nomal esophagus, the expression was higher in less differentiated and deeper invaded cases (P<0.05), but it had no correlations with other clinicopathological features such as age,sex, length and site of the tumor, regional lymph node metastases, and distant metastasis (P>0.05). Cases of esophageal carcinoma with lower COX-2 expression had longer survival time than those with higher COX-2 expression (P<0.01). CONCLUSIONS:COX-2 expression is higher in esophageal carcinoma than normal esophagus. COX-2 expression of esophageal carcinoma is higher in less differentiated and deeper invaded cases, but it has no correlation with age, sex, length and site of the tumor, regional lymph node metastases, and distant metastasis. Patients with lower COX-2 expression have longer survival time than those with higher COX-2 expression.     

Expression and clinical significance of PAK4 in non-small cell lung cancer

AIM: To investigate the expression and clinical significance of PAK4 in the cell lines and tissues of non-small cell lung cancer (NSCLC). METHODS: PAK4 expression in human bronchial epithelial (HBE) cells, NSCLC cell lines, NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry, real-time PCR and Western blot. Prognostic value of PAK4 expression was evaluated by Kaplan-Meier analysis and Cox regression. RESULTS: PAK4 was over-expressed in the NSCLC cell lines at both mRNA and protein levels compared with HBE cells (P<0.05). PAK4 was over-expressed in the NSCLC tissues at both mRNA and protein levels compared with adjacent non-tumor tissues (P<0.05). PAK4 was over-expressed in the metastatic NSCLC tissues compared with the primary NSCLC tissues (P<0.05). Higher PAK4 staining scores were positively correlated with differentiation, lymph node metastasis, distant metastasis, and clinical stage. Kaplan-Meier analysis and log-rank test showed that overall survival was significantly different between the patients with up-regulated PAK4 and the patients with down-regulated PAK4(P<0.05). PAK4 over-expression was associated with NSCLC progression.CONCLUSION: Increased PAK4 expression was associated with tumor invasion, metastasis and prognosis in the patients with NSCLC. PAK4 is an important prognostic marker and potential therapeutic target in NSCLC.     

Expression of ERK5 in colorectal cancer tissues and its correlation with distant metastasis in colorectal cancer patients

AIM: To investigate the expression of extracellular signal-regulated kinase 5 (ERK5) in primary colorectal cancer (CRC) and adjacent normal mucosa, and to analyze the relationship between ERK5 expression and clinicopathological parameters for exploring the functions of ERK5 in the occurrence and development of CRC. METHODS: The expression of ERK5 in carcinoma tissues and normal mucosa was examined by a set of tissue microarrays and the method of immunohistochemistry. The potential relationship between ERK5 expression and clinicopathological features was also analyzed. RESULTS: ERK5 expression was significantly higher in CRC tissues (134/338, 39.6%) than that in normal tissues (21/80, 26.2%; P<0.05). Overexpression of ERK5 in CRC tissues was significantly correlated with distant metastasis (P<0.05). However, no correlation between ERK5 expression and age at surgery, sex, tumor location, the depth of invasion, lymph node metastasis, TNM staging or differentiation grade was found (P>0.05). According to the Kaplan-Meier analysis, there is no significant difference in 5-year overall survival between the patients with ERK5 expression at high level and at low level. CONCLUSION: ERK5 protein is highly expressed in CRC with distant metastasis. This may be a promotive factor in the process of distant metastasis.     

Central role of GRP78 in growth of gastric carcinoma cells

AIM: To explore the effect of glucose-regulated protein 78 (GRP78) on the gastric carcinogenesis. METHODS: GPR78 expression patterns were examined in 34 specimens from gastric carcinoma patients using the immunohistochemistry (IHC) assay, and in 10 specimens using Western blotting analysis. In addition, the expression of GPR78 and cyclin D1 was detected in human gastric cancer cell lines SGC7901 and SGC7901-H78 (overexpressing GRP78) by Western blotting. RESULTS: By IHC assay, GRP78 was found to be highly expressed in the cytoplasm of gastric carcinomas as compared with the adjacent non-malignant tissues and corresponding normal tissues. GRP78 expression was positively correlated with gender and histological differentiation (P<0.05), but not with age, tumor stage and lymph node metastasis (P>0.05). Furthermore, we found that with the increased expression of GRP78 in SGC7901-H78 cells, the expression of cyclin D1 was also elevated. CONCLUSION: GRP78 might be a key player to be involved in the growth of gastric cancer.     

Measures of cell turnover (apoptosis and proliferation) and their association with survival in gastric cancer

AIM: To investigate the ratio of apoptotic index and proliferative index (AI/PI) in gastric cancer and their association with survival. METHODS: The apoptotic population and the proliferative population were quantitatively analyzed by flow cytometry. The proliferative cells were identified by confocal microscope and Kaplan-Meier method was used to analyze survival. RESULTS: AI and PI were strongly correlated with a Pearson coefficient of 0.58 (P<0.01). A stepwise decrease trend in AI/PI was noted in clinical pathological variables, including lymph node metastasis and beyond metastasis (P<0.05 for each). No statistically significant difference in AI/PI expression based on different survival times was observed. Using the median AI/PI of 0.245, the cells were divided into two groups (greater than and less than the median AI/PI). Using Kaplan-Meier survival curves and the Log-rank test, no statistic difference was found in two groups. The high expression of Ki-67 in tumor was found by confocal microscope. CONCLUSION: AI and PI are significantly correlated. A stepwise decrease trend in AI/PI may exist in tumor progression. AI/PI may not be good as a prognostic factor for cancer evaluation.     

Clinical significance of miRNA-326 expression in gastric cancer and effect of up-regulation of its expression on viability and apoptosis of gastric cancer cells

AIM: To investigate the clinical significance of microRNA-326 (miRNA-326) expression in gastric carcinoma and the effect of up-regulation of its expression on the viability and apoptosis of gastric cancer cells. METHODS: The expression of miRNA-326 in 55 tissue samples of gastric cancer was detected by RT-qPCR, and the relationship between the expression and the clinicopathological features was analyzed. The expression of miRNA-326 in gastric cancer BGC-823 cells was detected by RT-qPCR. The BGC-823 cells were transfected by liposome method, and randomly divided into normal control group (untransfected), mimic-NC group (transfected with negative control mimic) and miRNA-326 mimic group (transfected with miRNA-326 mimic). After up-regulation of miRNA-326 expression, the cell viability was measured by CCK-8 assay, and the apoptosis of the cells was analyzed by flow cytometry. The protein levels of matrix metalloprotein 9 (MMP-9), p21, cyclin D1, Bcl-2 and cleaved caspase-3 were determined by Western blot, and the mRNA expression of cyclin D1 was detected by RT-qPCR. Whether CCND1 (the gene of cyclin D1) was the target gene of miRNA-326 was evaluated by dual-luciferase reporter assay. RESULTS: The expression of miRNA-326 in the gastric cancer tissues was significantly lower than that in the adjacent tissues (P<0.05). The miRNA-326 expression had a significant correlation with the tumor size, lymph node metastasis, differentiation, and clinical stages (P<0.05), but it had no correlation with the age and sex of the patients. Moreover, the expression of miRNA-326 was also closely related to the survival rate of the patients (P<0.05). The expression of miRNA-326 in the BGC-823 cells was significantly lower than that in the normal gastric mucosa GES-1 cells (P<0.05). Compared with normal control group, the expression of miRNA-326 in mimic-NC group did not change significantly, while that in miRNA-326 mimic group was increased significantly (P<0.05). Compared with normal control group, the cell viability in miRNA-326 mimic group was significantly decreased, and the apoptosis was increased (P<0.05). In addition, compared with normal control group, the protein levels of MMP-9, cyclin D1 and Bcl-2, and the mRNA expression of cyclin D1 in miRNA-326 mimic group were decreased, while the protein levels of p21 and cleaved caspase-3 were increased (P<0.05). However, no significant difference of above protein and mRNA levels between mimic-NC group and normal control group was observed. Compared with mimic-NC+miR-326 mimic group, the activity of luciferase in the cells transfected with pmiR-CCND1-WT plasmid was significantly decreased (P<0.05), but that in the cells transfected with pmiR-CCND1-Mut plasmid did not change significantly. CONCLUSION: The expression level of miRNA-326 in gastric cancer tissues is low, and it may promote cell viability and inhibit cell apoptosis by targeting CCND1.     

Expression of Foxp3+ Tregs and PD1 in gastric cancer tissues and their correlation with clinicopathological factors and prognosis

AIM: To investigate the expression of Foxp3⁺ regulatory T cells (Foxp3⁺ Tregs) and programmed death receptor 1 (PD1) in gastric cancer tissues and their association with clinicopathological factors and prognosis of the patients. The correlation between the 2 molecules was also analyzed at the same time. METHODS: The tumor sections from 111 gastric cancer patients were stained for Foxp3 and PD1 by the method of immunohistochemistry. The associations of the expression levels of these 2 molecules with clinicopathological factors involved in the disease progression and prognosis were statistically analyzed. The relationship of their expression was detected. RESULTS: Foxp3⁺ Tregs and PD1 were expressed in the gastric cancer tissues, and PD1 was expressed in the tumor infiltrating lymphocytes (TILs). The expression of Foxp3 and PD1 was correlated with lymph node metastasis, clinicopathological stage and prognosis of gastric cancer patients. The expression of these 2 determinants in the patients with lymph node metastasis and an advanced clinicopathological stage was distinctly higher (P <0.05). The patients with positive expression of the 2 indexes presented a lower overall survival rate and worse prognosis (P <0.05). A significantly positive correlation between the infiltration of Foxp3⁺ Tregs and the expression of PD1⁺ TILs was also observed (P <0.01).CONCLUSION: Foxp3⁺ Tregs and PD1⁺ TILs co-infiltrate in the gastric cancer tissues, which can be used as biological markers to predict the disease progression and prognosis.     

Relationship between proliferation,DNA proliferative fraction,DNA ploidy and survival in gastric cancer patients

AIM: To evaluate the relationship between cell proliferation, DNA proliferative fraction (S+G2/M), DNA ploidy, biological features and survival in gastric cancer patients. METHODS: Proliferation, DNA proliferative fraction and DNA ploidy were analyzed by flow cytometry using standard techniques. RESULTS: No correlation between proliferation and DNA proliferative fraction (P>0.05) was observed. Likewise, there was no correlation between proliferation, DNA proliferative fraction and survival (P>0.05), nor was there a difference between proliferation, DNA ploidy and clinical pathological variables (P>0.05). Using Kaplan-Meier survival curves and the Log-rank test, statistic difference was found in patients with DNA diploid tumors and those with DNA aneuploid tumors (P<0.05). CONCLUSION: Proliferation and DNA proliferative fraction in gastric cancer do not appear to correlate with survival, but DNA ploidy can be used as a prognostic factor in gastric cancer.     

Expression of KDM5B gene in breast cancer and its clinical significance

AIM:To investigate the expression of KDM5B gene in breast cancer tissues and its relationship with clinical data and prognosis of the patients. METHODS:Data sets of breast cancer were collected from The Cancer Genome Atlas (TCGA) database, and KDM5B mRNA expression profiles were downloaded. The mRNA expression of KDM5B in breast cancer tissues and adjacent tissues was detected by real-time PCR. The cases were divided into high expression group and low expression group according to the median expression of KDM5B, and the relationship with clinical data and case characteristics were analyzed. The relationship between KDM5B and prognosis of breast cancer patients was analyzed by Kaplan-Meier plotter. RESULTS:The expression of KDM5B in breast cancer tissues was significantly higher than that in normal breast tissues (P<0.01). In TCGA breast cancer data, the expression of KDM5B was significantly correlated with human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), age, histopathological type and lymph node metastasis (P<0.01), but not with progesterone receptor (PR), menopause and distant metastasis. The expression of KDM5B was significantly correlated with HER2, age and lymph node metastasis, but not with ER, PR, menopause, pathological type and distant metastasis. The higher the expression of KDM5B, the shorter the total survival time and the disease-free survival time of breast cancer patients. CONCLUSION:KDM5B is over-expressed in breast cancer tissues and correlated with prognosis of the patients. KDM5B expression is significantly correlated with HER2, age and lymph node metastasis. KDM5B may play an important role in the development of breast cancer.     

Correlation between E-cadherin and FOXO3a expression in gastric can-cer tissues and cells

AIM: To investigate the expression of E-cadherin and forkhead box protein O3a (FOXO3a) in gastric cancer tissues and cells, and its correlation with cell viability. METHODS: The expression of E-cadherin and FOXO3a was detected by immunohistochemical staining in 53 specimens of gastric cancer tissues and their adjacent tissues, and the relationship between their expression and clinicopathological characteristics were analyzed. E-cadherin-over-expressing gastric cancer AGS cells were constructed by lentivirus-mediated cell transfection, and the protein expression of E-cadherin and FOXO3a was detected by immunocytochemistry method. The expression of E-cadherin, FOXO3a, Akt, Bcl-2 and Bax was determined by Western blot. The cell viability was detected by CCK-8 assay. RESULTS: The positive expression rates of E-cadherin and FOXO3a proteins in gastric cancer tissues were both significantly lower than those in their adjacent tissues (P<0.05). E-cadherin positive expression in gastric cancer tissues was significantly related to tumor grade and TNM stage (P<0.05), but not related to age, sex, location, T stage or lymph node metastasis. FOXO3a positive expression was significantly related to tumor grade (P<0.05), but not related to age, sex, location, TNM stage, T stage or lymph node metastasis. The expression of E-cadherin was positively correlated with FOXO3a expression in gastric cancer tissues (r=0.376, P=0.003). After over-expression of E-cadherin, the viability of gastric cancer AGS cells was significantly inhibited, the expression of FOXO3a, Bcl-2 and Bax was significantly increased, and the expression of Akt was significantly decreased. CONCLUSION: E-cadherin and FOXO3a are involved in the development of gastric cancer, and E-cadherin may affect the viability of gastric cancer cells by regulating Akt/FOXO3a signaling pathway.     

Expression of Tpl-2 in colorectal carcinogenesis

AIM: To analyze the relationship between Tpl-2 (tumor progression locus 2)expression and clinicopathological parameters of colorectal carcinoma by investigating the expression of Tpl-2 in adjacent normal mucosa, colorectal adenomas and colorectal carcinoma. METHODS: Tpl-2 expression in normal mucosa, adenoma and carcinoma was examined and compared in a set of tissue microarrays by immunohistochemistry. The potential relationship between Tpl-2 expression and clinicopathological features was analyzed. RESULTS: The expression of Tpl-2 in carcinoma was significantly increased compared to the adenoma and normal mucosa (P<0.01). No significant difference was detected between the adenoma and normal mucosa (P>0.05). Meanwhile, the correlation between Tpl-2 expression and lymph node metastasis (N stage) and TNM stage (P<0.05) was observed. However, the correlation between the Tpl-2 expression and clinicopathological features of colorectal cancer including sex, age, body mass index (BMI), tumor size, histological differentiation, invasive depth (T stage),distant metastasis(M stage) and K-ras mutation (P>0.05) was not found. CONCLUSION: Tpl-2 has a relevance to the development of colorectal cancer as a promotive factor in the colorectal carcinogenesis.     

Clinical significance and prognostic value of β-catenin expression in colonic adenocarcinoma

AIM: To observe the expression of β-catenin in colonic adenocarcinoma and to investigate its clinical significance and prognostic value. METHODS: The integrated clinical and follow-up data of 52 patients, who were undergone radical operation, were retrospectively analyzed from June 2000 to June 2004 in our hospital. The paraffin-embedded tissues of 52 colonic adenocarcinoma specimens and 20 cases of normal paraneoplastic colonic mucous tissues were detected for β-catenin expression by immunohistochemical method. The relationships between β-catenin and clinical variables and prognostic value were statistically analyzed. RESULTS: β-catenin was normally expressed in all 20 normal cases. In the cases of colonic adenocarcinoma, the abnormal expression rate of β-catenin was 71%. The abnormal expression of β-catenin did not correlated with gender, age, histological differentiation and blood CEA (P>0.05), but it was correlated with lymph node metastasis and clinical stage (P<0.05). The abnormal expression of β-catenin were also correlated with the postoperative survive time (P<0.05). CONCLUSION: The abnormal expression of β-catenin is correlated with the lymph node metastasis and clinical stage, and the abnormal expression is an important adverse prognostic factor for survival in the patients with colonic adenocarcinoma. β-catenin may be a molecular prognostic marker in the patients with colonic adenocarcinoma.     

Analyzing clinical characteristic of miR-196b in human colorectal cancer using TCGA and effect of miR-196b on 5-FU resistance of CRC cell line

AIM: To investigate the clinical characteristics of microRNA (miR)-196b in colorectal cancer (CRC) and to study its biological function in 5-fluorouracil (5-FU) resistance. METHODS: miRNA sequence dataset and the corresponding clinical data of CRC patients were downloaded from The Cancer Genome Atlas (TCGA). Expression level and clinical characteristics of miR-196b in CRC patients were analyzed using SPSS 17.0. CRC cell line overexpres-sing miR-196b was established using transient transfection method. MTS test was used to evaluate the effect of miR-196b overexpression on 5-FU resistance. RESULTS: miR-196b expression was associated with lymph node metastasis and TNM stage (P<0.05), but not related with age and sex. Lymph node metastasis and distant metastasis were independent prognostic factors for rectal patients (P<0.05). The expression level of miR-196b was not associated with survival condition of rectal patients. The viability of the cells overexpressing miR-196b treated with different concentrations of 5-FU was significantly higher than that in control group (P<0.05). CONCLUSION: miR-196b may be a potential biomarker of TNM stage and lymph node metastasis in CRC. miR-196b increases the 5-FU resistance of CRC cells.     

Study of annexin A2 expression in gastric cancer by proteomics and tissue microarray

AIM: To investigate the differential expression of annexin A2 (ANXA2) in gastric carcinoma and to analyze the relationship between ANXA2 expression and clinicopathological parameters of gastric carcinoma. METHODS: Pure gastric adenocarcinoma cells (GAC) and normal gastric epithelial cells (NGEC) in 15 patients with gastric cancer were acquired by laser capture microdissection (LCM). All peptide specimens after trypsin digestion were labeled with ¹⁸O/¹⁶O. Quantitatively identification of differential expression of the proteins betweem GAC and NGEC was performed by Nano-RPLC-MS/MS. The expression of ANXA2 in the 2 kinds of tissues was detected by Western blotting. Tissue microarray containing 75 pairs of gastric carcinoma and para-carcinoma tissues was used and the expression of ANXA2 in these specimens was detected by the method of immunohistochemistry (IHC). The relationship between ANXA2 expression and clinicopathological parameters of the pateints with gastric carcinoma was analyzed. RESULTS: A total of 78 differential proteins were identified and ANXA2 was up-expressed in GAC (2.32∶ 1), which was confirmed by Western blotting (P<0.01). The results of IHC showed that the correlations between the expression level of ANXA2 protein and invasive depth (T stage), lymph node metastasis (N stage), histological differentiation, TNM stage and the size of tumor were observed (P<0.01), but the correlations between the ANXA2 expression and sex, age and distant metastasis (M stage) were not found (P>0.05). CONCLUSION: The up-expressed ANXA2 may play an important role in the biological behavior of gastric cancer.     

Relationship between the expression of MMP-2, TIMP-2 and VEGF-C in hepatocellular carcinoma with or without lymph node metastasis

AIM: To investigate the relationship between the expression of MMP-2, TIMP-2 and VEGF-C in hepatocellular carcinoma (HCC) with or without lymph node metastasis. METHODS: The expression of MMP-2, TIMP-2 and VEGF-C in 44 cases of HCC were examined using immunohistochemistry methods (SP).RESULTS: The positive expression of MMP-2, TIMP-2 and VEGF-C was associated with lymph node metastasis of HCC (P<0.05). CONCLUSIONS: There was a significant correlation between the high-expression of MMP-2 and VEGF-C, and the low-expression of TIMP-2 in lymph node metastasis of HCC. VEGF-C is an important factor promoting lymph node metastasis of HCC. The expression of MMP-2, TIMP-2 and VEGF-C may have important value in determining lymph node metastasis and prognosis of HCC.