Clinical significance and prognostic value of extracellular signal-regulated kinases in epithelial ovarian cancer

AIM: To investigate the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) in epithelial ovarian cancer and to analyze the correlation between the expression of p-ERK and prognosis of epithelial ovarian cancer patients. METHODS: The samples of normal ovarian tissues, benign ovarian tissues and ovarian carcinoma were collected. The expression of p-ERK in each sample was detected by Western blotting. Assemble clinical data and survival were analyzed with Kaplan-Meier method and Cox regression. RESULTS: The expression level of p-ERK in ovarian carcinoma was significantly higher than that in benign ovarian tissues and in normal ovarian tissues. The overexpression of p-ERK protein was significantly higher in stage Ⅲ/Ⅳ disease than that in stage I/II disease. No difference of p-ERK expression level between the benign ovarian tissues and the normal ovarian tissues was observed. The overexpression of p-ERK was found more often in poorly-differentiated ovarian cancer. Compared with serous carcinoma of ovary, the expression level of p-ERK was similar in undifferentiated adenocarcinoma. The expression level of p-ERK was low in endometrioid carcinoma of ovary and mucinous carcinoma of ovary. The expression level of p-ERK was negatively correlated with the survival time. Increased p-ERK expression was strongly correlated to the poor survival. Shorter survival time was significantly associated with p-ERK expression, residual tumor, stage, grade and chemotherapy course. Shorter survival time was not significantly correlated with tumorous pathology. CONCLUSION: p-ERK is a key regulation kinase involved in epithelial ovarian cancer. The expression level of p-ERK seems to have a prognosis value in epithelial ovarian cancer.     

Vasculogenic mimicry and E-cadherin expression in epithelial ovarian cancer

AIM: To explore whether vasculogenic mimicry (VM) exists in human epithelial ovarian cancer (EOC), and to elucidate the relationship between E-cadherin (E-cad) expression and VM. METHODS: The E-cad expression and VM in 80 specimens of EOC and 20 specimens of benign ovarian epithelial tumor tissues were detected by the methods of immunohistochemical and histochemical staining. RESULTS: The positive rates of VM and E-cad protein in EOC were 57.4% and 48.7%, respectively.The positive rates of VM and E-cad protein in benign epithelial tumor tissues were 0% and 75.0%, respectively.There was a significant difference between the two groups (P<0.05 or P<0.01). The E-cad expression and VM in EOC was significantly related to differentiation, metastasis to abdominal organ and lymphnode, and PTNM stage (P<0.05). A negative relationship between the expression of E-cad and VM (r=-0.578,P<0.01) was also observed. PTNM stage, metastasis to abdominal organ and lymphnode, the expression of E-cad and VM were independent prognosis factors of EOC patients after total correction (P<0.05). The five-year survival rate between VM-positive group and VM-negative group was significantly different (4.3% vs 88.2%), while the five-year survival rate was significantly lower in E-cad-negative group than that in E-cad-positive group (9.8% vs 71.8%). CONCLUSION: EOC with VM has a poor differentiation and a bad clinical prognosis. The levels of VM and E-cad correlate with the progression and prognosis of EOC.     

Correlation between expression of ALDH1/ABCG2 and microvessel formation in epithelial ovarian cancer

AIM: To elucidate the correlation between the expression of aldehyde dehydrogenase 1 (ALDH1)/ATP-binding cassette subfaminly G member 2 (ABCG2) and microvessel density (MVD) in epithelial ovarian cancer (EOC).METHODS: In 198 specimens of EOC and 60 specimens of ovarian benign epithelial tumor tissues, the protein expression of ALDH1/ABCG2 and CD105 (microvessel marker) was detected by immunohistochemical staining.RESULTS: The positive rates of ALDH1 and ABCG2 in the EOC were 64.1% and 61.6%, respectively, while the positive rates in benign epithelial tumor tissues were 8.3% and 6.7%, respectively, and there were significant differences between them (P<0.05). In EOC and benign epithelial tumor tissues, the MVD were 22.6±9.7 and 5.03±3.35, respectively, and the difference was also significant (P<0.05). The expression of ALDH1 and ABCG2 in EOC was significantly related to differentiation, FIGO stage,and abdominal organ and lymph node metastasis (P<0.05). MVD had correlation with differentiation, FIGO stage, ascite, and abdominal organ and lymph node metastasis (P<0.05). MVD had positive correlation with the expression of ALDH1 and ABCG2 (P<0.01). There was also a positive correlation between the expression of ALDH1 and ABCG2 (P<0.01). Over-expression of ALDH1/ABCG2 and MVD≥23 were related to the poor prognosis. The survival rates in ALDH1/ABCG2 positive and MVD≥23 groups were significantly lower than those in ALDH1/ABCG2 negative and MVD<23 groups (P<0.05). The FIGO stage, the expression of ALDH1/ABCG2 and MVD were indepen-dent prognosis factors of EOC (P<0.05).CONCLUSION: The results suggest that the expression of ALDH1/ABCG2 and MVD in EOC are related to differentiation, lymph node metastasis, clinical stage and prognosis. Combined detection of these indexes may play an important role in predicting the progression and prognosis of EOC.     

Expression of glypican-3 in hepatocellular carcinoma and its clinical significance

AIM: To study the expression of glypican-3 in hepatocellular carcinoma (HCC) tissues and to clarify its clinical significance. METHODS: The expression of GPC3 was detected in 59 cases of HCC and their para-cancerous tissues, 10 cases of intrahepatic cholangiocellular carcinoma (ICC), 11 cases of cirrhotic tissues and 14 cases of normal liver tissues (around haemangioma) by RT-PCR and immunohistochemical staining. The survival curves were constructed using Kaplan-Meier method and evaluated using the log-rank test. In addition, the Cox proportional hazards regression model was established to identify the factors that were independently associated with disease-free survival (DFS). RESULTS: The mRNA expression of GPC3 in the HCC tissues was significantly higher than that in the para-cancerous tissues (83.1% vs 35.6%, χ²=27.53, P<0.01). The protein expression of GPC3 in the HCC tissue was also higher than that in the para-cancerous tissues (78.0% vs 33.2%, χ²=24.97, P<0.01). The expression of GPC3 in ICC tissues, liver cirrhosis tissues and normal liver tissues was undetectable. Kaplan-Meier survival analysis indicated that the GPC3(+)HCC patients had worse 1-year DFS than that of GPC3(-) patients (33.6% vs 72.7%, P<0.05). The HCC patients with para-cancerous GPC3(+) also had worse 1-year DFS than that of the para-cancerous GPC3(-) patients (23.5% vs 40.1%, P<0.05). The DFS rate decreased significantly as the expression intensity of GPC3 increased. The Cox regression model analysis indicated that AFP(+) (odd ratio=0.372, 95% confidence interval: 0.140-0.900, P<0.05), tumor size (odd ratio=5.215, 95% confidence interval: 1.737-15.656, P<0.01), para-cancerous tissue GPC3(+) (odd ratio=0.226, 95% confidence interval: 0.085-0.599, P<0.01) and the intensity of GPC3 expression in HCC tissue (odd ratio=1.946, 95% confidence interval: 1.080-3.507, P<0.05) were the independent risk factors linked to DFS of patients. CONCLUSION: GPC3 protein is highly expressed in the HCC tissues,but not in ICC, cirrhotic liver and normal liver tissues. The expression of GPC3 in para-cancerous tissues and the intensity of GPC3 expression in HCC tissues are the important independent risk factors linked to DFS of patients.     

Expression of chemokine receptor CCR7 and VEGF-C is associated with prognosis of breast carcinoma

AIM: To explore the protein levels of chemokine receptor 7 (CCR7) and vascular endothelial growth factor (VEGF)-C in breast carcinoma, and to investigate the effects of CCR7 and VEGF-C on prognosis of breast carcinoma. METHODS: The protein expression levels of CCR7 and VEGF-C in the breast carcinoma tissues and normal breast tissues were detected by the method of immunohistochemistry. At the same time, the relationship between clinicopathologic characteristics and the protein expression of CCR7 and VEGF-C in the breast carcinoma tissues was analyzed. The relationship between the protein expression of CCR7 and VEGF-C and survival time of the breast cancer patients was estimated by Kaplan-Meier method.RESULTS: The positive expression rates of CCR7 and VEGF-C in the breast carcinoma tissues were significantly higher than those in the normal breast tissues (P<0.01). A positive correlation was observed between the protein expression of CCR7 and the protein expression of VEGF-C in the breast carcinoma tissues (r=0.613, P<0.01). The protein expression of CCR7 and VEGF-C was correlated with lymph node metastasis and TNM stage (P<0.05), but both were not related to patients' age, primary tumor size, estrogen receptor and progesterone receptor. The survival time of the patients with CCR7 and VEGF-C positive expression was significantly shorter than that of the patients without the expression (P<0.05).CONCLUSION: The positive expression of CCR7 and VEGF-C proteins is associated with the prognosis of breast cancer, and combined detection of CCR7 and VEGF-C protein expression levels may be helpful to judge the prognosis of breast cancer.     

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.     

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 Mnk2 protein expression and prognosis of patients with esophageal squamous cell carcinoma

AIM: To investigate the protein expression of mitogen-activated protein kinase-interacting kinase-2 (Mnk2) and its prognostic effect in the patients with resected esophageal squamous cell carcinoma (ESCC). METHODS: A total of 86 informative patients with surgically resected ESCC and 54 normal esophageal tissues were enrolled. Western blot and immunohistochemistry (IHC) were utilized to assess the protein expression of Mnk2, and its correlation with prognosis was statistically analyzed by the methods of Kaplan-Meier curve and Cox proportional hazard mode. RESULTS: The protein expression of Mnk2 was elevated in most of tumor tissues compared with the adjacent tissues. Clinicopathologic analysis showed that Mnk2 expression was significantly correlated with the TNM stage (P<0.05). Both disease-free survival (DFS) and overall survival (OS) of Mnk2 over-expression patients were shorter than those in Mnk2 negative expression group. Multivariate analysis confirmed that Mnk2 expression, as an independent and significant factor for both DFS and OS, predicted a poor prognosis of the patients with resected ESCC (P<0.05). CONCLUSION: The expression of Mnk2 was significantly related to the TNM stages, and might be a novel predictor for prognosis in ESCC.     

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.     

Role of multidrug resistance gene 1 polymorphism in prognosis of hepatocellular carcinoma patients treated with liver transplantation

AIM: To evaluate the relationship between three multidrug resistance gene 1 (MDR1) polymorphisms (C1236T, G2677A/T, C3435T) and the prognosis of hepatocellular carcinoma (HCC) in Chinese liver transplantation (LT) patients.METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotypes of MDR1 gene in 50 HCC patients treated with LT. The tumor-free survival and overall survival were compared among these patients according to the polymorphisms of MDR1 by Kaplan-Meier method, multivariate regression analysis was also performed.RESULTS: No significant association was found between C1236T, G2677T, C3435T and prognosis of these patients. But interestingly, 2677A carrier group had significantly higher tumor-free survival rate than 2677A noncarrier group (P<0.05). The multivariate regression analysis revealed that 2677A carrier genotype was one of the independent factors for predicting tumor-free survival (RR=0.143, P<0.01).CONCLUSION: MDR1 2677A carrier genotype is correlated with the tumor-free survival. MDR1 2677A carrier genotype may be a useful independent prognostic factor in HCC patients treated with LT.     

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.     

Prognostic significance of CUEDC2 expression in hepatocellular carcinoma

AIM: To investigate the expression of CUE domain-containing 2 (CUEDC2) in hepatocellular carcinoma (HCC) and to analyze its clinical prognostic significance. METHODS: Total 186 formalin-fixed paraffin-embedded tissues obtained from surgical HCC with detailed clinicopathological and follow-up data were used. The expression of CUEDC2 was detected by immunohistochemistry. The relationships between the expression of CUEDC2 and clinicopathological characteristics and prognosis were analyzed. RESULTS: The positive rate of CUEDC2 in HCC was 85.5% (159/186), among which, the low expression was 52.2% (97/186) and the high expression was 47.8% (89/186). CUEDC2 expression was correlated with serum alpha-fetal protein (AFP) level, tumor size, tumor number, tumor differentiation and TNM stage (P<0.05). Kaplan-Meier survival curves showed that the patients with high expression of CUEDC2 were associated with significantly shorter overall survival and recurrence-free survival than those with low CUEDC2 expression (P<0.05). Multivariate Cox regression analysis revealed 3 independent prognostic factors including CUEDC2 expression, serum AFP and tumor number. CONCLUSION: CUEDC2 was expressed in most HCC tissues, which was relevant to tumor growth, tumor differentiation and prognosis. CUEDC2 could be a novel valuable molecular marker to predict the HCC prognosis.     

Prognostic prediction of PTEN and Her-2 expression in breast cancer

AIM:To study the prognositic value of PTEN and Her-2 expression in primary breast cancer. METHODS:81 breast cancer specimens with 15 years follow-up were obtained from 1989 to 2004. Immunohistochemical methods were used to detect the expression of PTEN and Her-2 in 81 paraffin-embedded specimens. The correlation between expression of PTEN and clinipathological factors was discussed with the Chi-square test. The survival rate analysis results were calculated with Kaplan-meier method.Long-rank test and Cox model by SPSS 10.0 software. 〖JP+1〗RESULTS:(1) PTEN expression significantly affects 5-year and 10-year survival rate of breast cancer (P<0.01 and P<0.05), and significantly negative correlation with the Her-2 expression was observed. (2) The patients with negative PTEN combined with positive Her-2 expression had worse prognosis. (3) Tumor sizes, postoperative therapy and PTEN expression had significant relation with the 5-year survival rate (P<0.05), and ER, Her2 and PTEN expression had significant relation with the 10-year survival rate (P<0.05). CONCLUSION:PTEN and Her-2 expression significantly affects 5-year and 10-year survival rate in patients with breast cancer, and may be biomarkers and important prognostic factors in breast cancer.     

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 cyclin D1, RBL2/p130 and MCM7 in hepatocellular carcinoma

AIM: To investigate the expression and prognostic significance of cyclin D1, retinoblastoma-like protein 2(RBL2/p130) and minichromosome maintenance protein 7(MCM7) in hepatocellular carcinoma(HCC). METHODS: The expression of cyclin D1, RBL2/p130 and MCM7 in 44 HCC specimens, 26 adjacent noncancerous cirrhotic liver specimens and 18 normal liver specimens were detected by the method of immunohistochemistry. The correlations of cyclin D1, RBL2/p130 and MCM7 with the clinical parameters of HCC patients were analyzed. RESULTS: The positive expression rates of cyclin D1 and MCM7 in HCC were 68.2% and 72.7%, higher than those in normal livers and adjacent noncancerous cirrhotic livers(P<0.01). The positive expression rate of RBL2/p130 in HCC was 34.1%, lower than that in normal livers and adjacent noncancerous cirrhotic livers(P<0.01). The expression of MCM7 in HCC was positively correlated with the expression of cyclin D1(r=0.349, P<0.05), and negatively correlated with the expression of RBL2/p130(r=-0.421, P<0.01). The expression of cyclin D1 in HCC was negatively correlated with the expression of RBL2/p130(r=-0.435, P<0.01). The expression of MCM7 and cyclin D1 was associated with the integrity of tumor capsule, differentiation degree and TNM stage(P<0.05). The expression of MCM7 was also associated with tumor size and the value of alpha fetoprotein(AFP). The tumor size, the expression levels of MCM7 and cyclin D1 were correlated with the prognosis determined by multivariable analysis. The patients with positive expression of MCM7 and cyclin D1 had lower survival rate than those with negative expression(P<0.05). The patients with positive expression of RBL2/p130 had higher survival rate than those with negative expression(P<0.05). CONCLUSION: The abnormal expression of cyclin D1, RBL2/ p130 and MCM7 plays an important role in the development of HCC, indicating that monitoring their expression in HCC patients may be helpful to the judgment of prognosis.     

Effect of biological clock gene Timeless silencing on apoptosis and invasion of ovarian cancer SKOV3 cells

AIM:To evaluate the effect of biological clock gene Timeless (TIM) silencing on the apoptosis and invasion ability of human ovarian cancer SKOV3 cells. METHODS:The protein expression of TIM in the ovarian cancer tissues and normal ovarian tissues was detected by immunohistochemistry, and the correlation between the protein expression of TIM in ovarian cancer tissues and the pathological features was analyzed. The ovarian cancer SKOV3 cells were transfected with PBS (blank control group), control siRNA (siRNA control group) or TIM siRNA (TIM siRNA group). The protein expression of TIM, Bcl-2, Bax, MMP-2, MMP-9, caspase-3 and caspase-9 was determined by Western blot. The apoptosis was detected by flow cytometry. The invasion ability was measured by Transwell chamber test. RESULTS:The positive expression rate of TIM in the ovarian cancer tissues (84.0%) was significantly higher than that in the normal ovarian tissues (10.0%; P<0.01). TIM expression was associated with ovarian cancer differentiation, depth of invasion, lymph node metastasis and TNM stage (P<0.05), but was not associated with age and pathological type (P>0.05). The protein expression levels of TIM, MMP-2, MMP-9 and Bcl-2 in TIM siRNA group were significantly decreased as compared with control group and siRNA control group (P<0.01), and the protein expression of Bax, caspase-3 and caspase-9 in TIM siRNA group was significantly increased as compared with blank control group and siRNA control group (P<0.01). No significant difference of the protein expression of TIM, MMP-2, MMP-9, Bcl-2, Bax, caspase-3 and caspase-9 between blank control group and siRNA control group was observed (P>0.05). The apoptotic rate in TIM siRNA group was significantly higher than that in blank control group and siRNA control group (P<0.01), and that in blank control group and siRNA control group was not significantly different (P>0.05). The penetrated cell number in TIM siRNA group was significantly less than that in blank control group and siRNA control group (P<0.01), and that in blank control group and siRNA control group was not significantly different (P>0.05). CONCLUSION:Silencing of TIM gene in ovarian cancer SKOV3 cells by siRNA promotes apoptosis, and inhibits cell invasion.     

Clinical significance of KLF15 expression in human lung adenocarcinoma

AIM: To explore the clinical significance of Krüpple-like factor 15 (KLF15) protein expression in the patients with lung adenocarcinoma for exploring the therapeutic and prognositic biomarkers of lung cancer. METHODS: Four cases of lung adenocarcinoma tissues and matched adjacent tissues were collected from our hospital, and the expression of KLF15 protein in these tissues was analyzed by Western blot. At the same time, 72 cases of archived paraffin-embedded samples and clinical data of the patients with lung adenocarcinoma were also collected. The KLF15 protein expression in the archived paraffin-embedded lung adenocarcinoma samples was detected by immunohistochemical staining. The correlations between KLF15 protein expression and clinical characteristics of the patients including prognosis were also analyzed. In addition, the KLF15 protein was up-regulated in A549 cells, and then the effects of KLF15 protein on the viability of the cells were measured by CCK-8 assay. RESULTS: The protein expression of KLF15 in the 4 cases of lung adenocarcinoma tissues was significantly lower than that in matched paracancerous tissues. Fifty-three cases of lung adenocarcinoma specimens showed low expression or no expression of KLF15 protein in total 72 cases (73.6%). The 5-year survival rate of the patients with high expression of KLF15 protein in their specimens was higher than that of the patients with the low expression of KLF15 protein (P<0.01), and the expression of KLF15 protein was significantly correlated with the pathological staging (P<0.01) and T stage (P<0.01) of the patients with lung adenocarcinoma. Furthermore, the low expression of KLF15 protein was an important poor prognostic indicator of the patients. Up-regulation of KLF15 protein in the A549 cells significantly inhibited the growth of the cells. CONCLUSION: KLF15 inhibits the growth of lung adenocarcinoma cells. It could be used as a therapeutic target and a prognostic biomarker for the patients with lung adenocarcinoma.