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OBJECTIVE@#To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.@*METHODS@#Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.@*RESULTS@#The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).@*CONCLUSION@#S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.
Subject(s)
Animals , Mice , Humans , Adenocarcinoma of Lung/pathology , Cell Proliferation , Lung Neoplasms/pathology , Mice, Nude , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , S100 Proteins/geneticsABSTRACT
Purpose To analyze the expression and prognostic value of metastasis-associated protein 2 (MTA2) in epithelial ovarian carcinoma. Methods The expression of MTA2 protein was examined in 91 paraffin-embedded specimens by immunohistochemical SP method, and in fresh specimens by Western blot, and then combined with follow-up data for prognosis analysis. Results There was an increasing tendency in positive rate of MTA 2 expression from benign ovarian cysts (17.5％) to epithelial ovarian cancers (78.43％), and there were significant difference (χ2=33.328, P<0.001). The expression of the MTA2 was significantly correlated to FIGO stage and lymph node metastasis (both P<0.05). The relative expression of MTA2 in benign ovarian cysts and epithelial ovarian cancers was 0.58±0.05, and 1.22±0.10, respectively, and the difference was statistically significant (t=-22.274, P<0.001). The survival curve of patients with MTA2 (+) differed from the survival curve of patients with MTA2 (-) and the difference was statistically significant (χ2=10.203, P<0.05). The multiple factor analysis revealed that the expression of MTA2, FIGO stage and lymph node metastasis were independent prognostic factors for clinical outcome of epithelial ovarian cancer. Conclusion MTA2 may be involved in the progression and metastasis of epithelial ovarian cancer as an oncogene. Overexpression of the marker indicates poor prognosis of patients.
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Objective To detect the expression of CXCL8 in colorectal tumor tissues and marginal tissues,and analyze the correlation between CXCL8 and clinicopathological parameters. Methods Sixty colorectal cancer specimens and the mar-ginal tissues were collected from the colorectal cancer patients who were surgically removed in gastrointestinal surgery in Zhengzhou Central Hospital Affiliated to Zhengzhou University from November 2014 to November 2016 and were all confirmed by pathology. The expression of CXCL8 protein and mRNA in colorectal tumor tissues and marginal tissues was detected by im-munohistochemistry and real time fluorescent quantitation polymerase chain reaction respectively. Results The expression of CXCL8 mRNA in colorectal tumor tissues and marginal tissues was 157. 6 ± 26. 2 and 42. 7 ± 9. 6. The expression of CXCL8 mRNA in colorectal tumor tissues was higher than that in the marginal tissues(P < 0. 05). The positive expression rate of CXCL8 protein in the colorectal tumor tissue and marginal tissue was 83. 3％(50 / 60)and 25. 0％(15 / 60),respectively. The positive expression rate of CXCL8 in the colorectal tumor tissues was higher than that in the marginal tissues(χ2 = 41. 10,P <0. 01). The expression of CXCL8 in colorectal tumor tissues was correlated with lymph node metastasis and tumor staging(P <0. 01). The expression of CXCL8 in colorectal tumor tissues had not correlation with age,gender and differentiated degree colo-rectal tumor(P > 0. 05). Conclusion CXCL8 has high expression in colorectal cancer tissues,and it is closely related to the condition of lymph node metastasis and tumor staging in patients with colorectal cancer.
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Background: In English literature it is documented that the expression of ER and PR is low in Asian countries when compared to that of Western countries. HER2/neu over expression is uniform throughout the world. Studies have shown that triple-negative breast carcinomas are aggressive, likely to spread beyond the breast and recur after treatment. Aims and objectives: To correlate the expression of ER, PR and HER 2/neu with clinico-pathological parameters in infiltrating ductal carcinoma and other variants of breast carcinoma. To determine the clinicopathological parameters in triple negative cases. Methods: This is a prospective study for a period of two years in the Department of Pathology, Andhra Medical College, a tertiary care centre. We received 111 mastectomy specimens during this period out of which 52 patients were funded under Arogyasri and were subjected for ER, PR, HER2/neu receptor study. Results: In the present study total cases analyzed were 52. Infiltrating ductal carcinoma was 41/52 (78.84%) and other variants were 11/52 (21.15%). In our institute infiltrating duct cell carcinoma (NOS) type was the commonest type of carcinoma breast with significant group occurring in less than 45 years of age, 95 % of women were multipara with two or more children and triple negative tumors being 54.83%.In infiltrating ductal carcinoma ER, PR positive expression has no association with age and size of tumor. Their expression was higher in grade 1 tumors 83.3%.The ER,PR negative expression was more in size of tumor being greater than 2 cm; (92.5%),positive lymph nodes (51.8%) and stage II and stage III tumors (96.2%). HER2/neu negative expression was seen in 51.61% of cases. Triple negative receptor expression was seen in 54.83% of infiltrating ductal carcinoma. In the English literature medullary carcinoma is negative for HER2/neu expression but in the present study in 2 cases the expression for HER2/neu was positive. Conclusion: In the present study significant group occurred in less than 45 years of age presenting in advanced stage of the disease. Triple negative cases were seen in 54.8% cases of infiltrating duct cell carcinoma indicating bad prognosis.
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Background and purpose:Lung cancer is the leading cause of cancer-related deaths worldwide. Approximately 15%of all histological types consist of small cell lung cancer (SCLC). Chemotherapy is one of the major treatment methods. Though the current front-line standard chemotherapy regimen for SCLC is active in most SCLC cases, however, the disease recurs shortly after the ifrst successful treatment with multi-drug resistance phenotype. Our previously study showed that zinc ifnger protein X-linked (ZFX) was overexpressed in SCLC cells. This study aimed to investigate the expression of ZFX in SCLC tissues, and to clear their possible associations with clinical parameters and provide basis for therapy of SCLC. Methods:A total of 98 surgical specimens of small cell lung cancer were collected. The expression of ZFX was examined by quantiifcational real-time polymerase chain reaction in 78 specimens taken from patients with complete clinical data. Results:The expression of ZFX was signiifcantly increased in extensive stages than in limited stages. The expression of ZFX was associated with tumor stage, the sensitivity of chemotherapy, and survival times (all P0.05). Conclusion: ZFX expression might be associated with the development of SCLC, and may be a potential prognosis predictor.
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Objective To investigate the expression of serum vascular endothelial growth factor(VEGF) in patient with bladder transitional cell carcinoma (BTCC) and its relationship with clinicopathological parameters.Methods The clinical data of 68 patients with BTCC who underwent surgical treatment was retrospectively analyzed,the healthy subjects was considered as control group,the serum VEGF levels of patient with BTCC and healthy subjects were detected by ELISA and compared.Results The VEGF levels of bladder cancer group was (317.62 ±89.47) ng/L,and was significantly higher than that of the control group [(53.08 ± 17.40) ng/L] (t =16.017,P ＜0.01).The VEGF levels of invasive cancer group and pathological grading of high-level group were respectively higher than the superficial tumor group and pathological grading of low-level group,compared the difference was significant (t =8.191,6.230,all P ＜0.01).The VEGF level was not significantly difference between the different age groups,gender groups and tumor size groups(t =0.423,0.528,1.307,all P ＞ 0.05).Conclusion The serum VEGF levels are high expression in patients with BTCC,the VEGF levels are closely related to clinical stage and histological grade.The high expression of serum VEGF shows the invasion and progression of BTCC.
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Background: Smad4, Smad6 and Smad7 are important molecules in TGF-beta pathway, which plays an important role in pancreatic ductal adenocarcinoma (PDAC) biology. Aims : This study examined the expression profiles of Smad4, Smad6 and Smad7 mRNA in patient samples of PDAC and their relationship to Smad protein expression, SMAD4 gene mutations, clinicopathological parameters and patient survival. Settings and Design: Surgically resected, paired normal and tumor tissues of 25 patients of PDAC were studied. Materials and Methods: Protein and mRNA levels were assessed by immunohistochemistry and RT-PCR, respectively. Statistical Methods: Statistical analysis was done using Student's t-test, Pearson's chi-square test, Spearman's Rank Correlation, Pearson's Correlation test and Kaplan-Meier Logrank test. Results: While there was a highly significant difference in the protein levels of all three Smads in tumor as compared to normal samples, mRNA levels were significantly different only for Smad4. Protein levels did not correlate significantly with mRNA levels for any of the three Smads. The mRNA levels of Smad4 and Smad6, Smad4 and Smad7, and Smad6 and Smad7 in tumor samples showed a significant positive correlation. The relationship of Smad4 mRNA expression to SMAD4 gene status and Smad4 protein expression was discordant and there was no significant correlation between mRNA expression and clinicopathological parameters and patient survival. Conclusion : The absence of concordance between SMAD4 gene status, mRNA expression and Smad4 protein expression suggests the presence of other regulatory mechanisms in Smad4 transcription and translation in PDAC.
Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Adult , Aged , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/secondary , Female , Humans , Immunoenzyme Techniques , Male , Middle Aged , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Prognosis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Smad4 Protein/genetics , Smad4 Protein/metabolism , Smad6 Protein/genetics , Smad6 Protein/metabolism , Smad7 Protein/genetics , Smad7 Protein/metabolism , Survival RateABSTRACT
PURPOSE: Insulin-like growth factor binding protein (IGFBP-3) and phosphatase and tensin homolog (PTEN) are tumor-suppressor genes that may be involved in breast tumorigenesis. However, the roles of these genes in the regulation of breast cancer growth or progress are unclear. In this study, we aimed to find any correlation between the reduction of IGFBP-3 or PTEN protein expression in cancer tissues and the clinicopathological parameters in breast cancer. METHODS: We collected both cancer and adjacent normal tissues from 46 breast cancer patients (from January 1 to December 31, 2006), and checked the IGFBP-3 and PTEN protein levels in cancer and adjacent normal tissues using Western immunoblot. We evaluated the correlation of reduction status of IGFBP-3 and PTEN protein expression with variable clinicopathological parameters. RESULTS: The frequency of IGFBP-3 and PTEN protein reduction in cancer tissue, compared to adjacent normal tissue, was 63.0% and 34.8%, respectively. And in 87.5% of patients, who showed significant PTEN reduction, IGFBP-3 protein expression was reduced in cancer tissues. In contrast, IGFBP-3 protein reduced in only 50% of patients who didn't show PTEN reduction. However, we did not find any significant correlation between reduction of IGFBP-3 or PTEN expression in cancer tissue and variable clinicopathological parameters. CONCLUSION: The IGFBP-3 and PTEN genes were expressed in all breast cancer tissues. Nonetheless, we did not find any significant relationship between reduction of IGFBP-3 or PTEN expression and the clinicopathological parameters in this study. Therefore, further studies are needed to document the roles of IGFBP-3 and PTEN genes in breast cancer growth or progress.
Subject(s)
Humans , Blotting, Western , Breast , Breast Neoplasms , Carrier Proteins , Cell Transformation, Neoplastic , Insulin-Like Growth Factor Binding Protein 3 , Microfilament Proteins , PTEN PhosphohydrolaseABSTRACT
PURPOSE: In the current study, the relation between the clinicopathological parameters and levels of the amplification of the c-met and E-cadherin genes were investigated in patients with an advanced gastric carcinoma. METHODS: The levels of amplification of the c-met and E-cadherin genes in 44 advanced gastric carcinoma patients were retrospectively investigated using RT-PCR. The relationships between the levels of amplification of these genes and the clinicopathological parameters were evaluated using univariate and multivariate analyses. RESULTS: Seventeen (38.6%) and 13 (29.5%) of the 44 advanced gastric carcinoma patients were evaluated as having amplification of the c-met gene and down-regulation of the E-cadherin gene, respectivly. The amplification of c- met gene was significantly correlated with serosal invasion, lymph node metastasis and neural invasion, whereas the down-regulation of the E-cadherin gene was significantly correlated with the diffuse type of gastric carcinoma by Lauren's calssification, and neural invasion. CONCLUSION: The levels of the c-met and E-cadherin gene amplifications may be a powerful aids in evaluating the metastatic potential and prognosis in patients with advanced gastric cancer.