Jingshu Geng

Harbin Medical University, Charbin, Heilongjiang Sheng, China

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Publications (25)60.44 Total impact

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    ABSTRACT: The aim of this study is to investigate the expression of ribosome-binding protein 1(RRBP1) in invasive breast cancer and to analyze its relationship to clinical features and prognosis. RRBP1 expression was studied by Real-time quantitative PCR and western blotting using pair-matched breast samples and immunohistochemical staining using a tissue microarray. Then the correlation between RRBP1 expression and clinicopathologic features was analyzed. RRBP1 mRNA and protein expression were significantly increased in breast cancer tissues compared with that in normal tissues. The protein level of RRBP1 is proved to be positively related to histological grade (P=0.02), molecular subtype (P=0.048) and status of Her-2 (P=0.026) and P53 (P=0.015). We performed a grade-stratified analysis of all patients according to the level of RRBP1 expression and found that RRBP1 overexpression highly affected OS in patients with early-stage (I and II) (P=0.042). Furthermore, patients of Her-2 positive with negative RRBP1 expression had longer overall survival (OS) than ones with positive RRBP1 expression (P=0.031), lymph node metastasis (LNM, P=0.002) and RRBP1 expression (P=0.005) were independent prognosis factors for OS by multivariate analysis. RRBP1 is a valuable prognostic factor in Her-2 positive breast cancer patients, indicating RRBP1 may be a potentially important target for the prediction of prognosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Cancer Science 04/2015; 106(6). DOI:10.1111/cas.12666 · 3.52 Impact Factor
  • Shuzhe Deng · Huilei Qiu · Hongtao Song · Jingshu Geng ·

    Zhonghua bing li xue za zhi Chinese journal of pathology 12/2014; 43(12):856-8. DOI:10.3760/cma.j.issn.0529-5807.2014.12.019
  • Zhennan Tian · Guodong Yao · Hongtao Song · Yang Zhou · Jingshu Geng ·
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    ABSTRACT: Background: Insulin-like growth factor (IGF) pathway has been suggested as a new molecular target for the treatment of cancer including Non-small cell lung cancer (NSCLC). We postulated that IGF-2 receptor (IGF2R) may be associated with treatment response and prognosis of NSCLC patients receiving chemotherapy. Methods: A total of 464 patients with inoperable advanced stage of NSCLC were enrolled. All patients received platinum-based chemotherapy. Meanwhile, the IGF2R expression in tumor samples was detected by Immunohistochemical analysis. The IGF2R expression was inhibited in several human NSCLC cell lines (H292, A549, NCI-H460, Calu-3 and NCI-H23) after small interfering RNA (siRNA) transfection and the cellular biology behavior were evaluated. Results: Of all NSCLC patients, 204 had high IGF2R expression and 260 had low IGF2R expression. The low IGF2R expression was significantly associated with the smoking status, higher tumor stage, and poorer differentiation status of these patients. Notably, we found that the low IGF2R expression was closely associated with the chemotherapy response in NSCLC patients. Patients with low IGF2R expressions had a poorer prognosis than those with high IGF2R expressions. IGF2R inhibition by si-RNA technique in NSCLC cell lines increased the proliferation, migration and invasion abilities, but reduced the apoptosis rate. IGF2R silencing significantly enhanced the chemo-resistance of NSCLC cell lines to cisplatin treatment. Conclusion: The IGF2R expression in tumor is associated with the chemotherapy response and prognosis of Patients with advanced NSCLC. © 2014 S. Karger AG, Basel.
    Cellular Physiology and Biochemistry 10/2014; 34(5):1578-1588. DOI:10.1159/000366361 · 2.88 Impact Factor
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    ABSTRACT: S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, can induce the apoptosis of many types of cancer cells through the MAPK signaling pathway. The TGF-β signaling pathway also plays a pivotal role in the process of oncogenesis, and has a certain crosstalk with the MAPK pathway. In the present study, hepatocellular carcinoma cell line HepG2 with an intact TGF-β signal and colon cancer cell line SW620 with an imperfect TGF-β signal were selected to ascertain whether SAMC induces the apoptosis of cancer cells by TGF-β signaling. In both cell lines treated with MAPK inhibitors and SAMC, an increased apoptosis rate was observed by electron microscopy, TUNEL and flow cytometric assays. Immunohistochemistry and western blot assays showed that SAMC induced the apoptosis of cancer cells by activating TGF-β1, TβRII, p-smad2/3, smad4 and smad7 signals, and promoting Bim expression while decreasing Bcl-2 expression and finally activating the mitochondrial apoptosis pathway proteins caspase-3 and caspase-9 in the HepG2 cell line. In contrast, in the SW620 cell line, the apoptosis induced by SAMC only affected TGF-β1 and smad7 signals, and promoted the expression of Bax and Bad and finally activated the mitochondrial apoptosis pathway protein caspase-9. When we compare the apoptosis rate in both cell lines, a significantly lower apoptosis rate was noted in the SW620 cell line than the rate noted in the HepG2 cell line. In summary, SAMC induces the apoptosis of cancer cells by activating the TGF-β signaling pathway, after MAPK signaling is inhibited.
    Oncology Reports 06/2014; 32(3). DOI:10.3892/or.2014.3295 · 2.30 Impact Factor
  • Hongtao Song · Zhennan Tian · Yu Qin · Guodong Yao · Songbin Fu · Jingshu Geng ·
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    ABSTRACT: The molecular mechanism underlying the invasiveness of colorectal cancer (CRC) cells remains largely unknown. Here, we found that astrocyte elevated gene-1 (AEG-1) was significantly upregulated in CRC tissues, compared with the adjacent normal tissues from human patients. Ectopic expression of AEG-1 enhanced the invasive ability of CRC cells, while small interfering RNA (siRNA)-induced knockdown of AEG-1 inhibited the invasive ability of CRC cells. Transcription, protein levels, and secretion of matrix metalloproteinase 9 (MMP9), all increased by AEG-1 overexpression in CRC cells, and all decreased by AEG-1 inhibition. Suppression of endogenous MMP9 abrogated the effects of AEG-1 on invasiveness, without affecting AEG-1 levels. Taken together, these findings suggest that AEG-1 contributes to CRC invasiveness and metastasis by enhancing MMP9 activity. Thus, AEG-1 appears to be a novel therapeutic target for preventing the metastasis of CRC.
    Tumor Biology 04/2014; 35(7). DOI:10.1007/s13277-014-1883-3 · 3.61 Impact Factor
  • Yina Gao · Jingshu Geng · Xuan Hong · Jiping Qi · Yang Teng · Yang Yang · Di Qu · Gongyan Chen ·
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    ABSTRACT: To investigate the correlation among p300, CBP and MLL expression and the clinicopathological characteristics in resected SCLC patients. Two hundred and twenty-two resected SCLC patients were included in this study. We evaluated p300, CBP and MLL expression by immunohistochemistry. Patients with high p300 expression had shorter OS and DFS than those with low p300 expression (p = 0.01; p = 0.009, respectively). The patients with CBP-positive tumors had significantly lower OS and DFS than those with CBP-negative tumors (p = 0.005 and p = 0.007, respectively). Moreover, the p300- and CBP-positive (+) group had a significantly poor OS and DFS. The multivariate Cox regression analysis showed that high p300 and CBP expression are independent markers of poor overall survival (p = 0.006; p = 0.017, respectively) in operable SCLC patients. High p300 and CBP expression are independent prognostic markers of poor overall survival for resected SCLC patients. The combination of p300 and CBP expression may be useful in identifying patients with increased risks of cancer recurrence of SCLC.
    International journal of clinical and experimental pathology 02/2014; 7(2):760-7. · 1.89 Impact Factor
  • Fang Yang · Yina Gao · Jingshu Geng · Di Qu · Qiuyue Han · Jiping Qi · Gongyan Chen ·
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    ABSTRACT: Objectives: The central issue in this study is to investigate the expression of Sex determining region Y-BOX2 (SOX2) and fibroblast growth factor receptor 1 (FGFR1), evaluate their clinicopathological variables and prognostic significance in small cell lung cancer (SCLC). Methods: Specimens from 222 SCLC patients and 53 adjacent normal lung tissues were detected by the immunohistochemistry for SOX2 and FGFR1 expression. The relationship between the expression of both markers and survival status was determined. Results: Overexpression of SOX2 and FGFR1 were revealed in SCLC tumors than in normal tissues (P<0.05). SOX2 expression was associated with clinical stage (P=0.014) and lymph node status (P=0.041). Besides, FGFR1 expression was significantly higher in ever smokers (P=0.030) and late stage SCLC (P=0.005). SOX2, FGFR1 and TNM stage were independent prognostic factors for overall survival (OS) and Recurrence-free survival (RFS) by multivariate analysis. In stage I patients, only overexpression of SOX2, but not of FGFR1, predicted poor OS (0.027) and RFS (P=0.013). According to the expression of SOX2 and FGFR1, patients were categorized into three groups. Patients with elevated expression of both markers belonged to the group with the shortest RFS (P<0.0001) and OS (P<0.0001). Conclusions: Increased expression of SOX2 and FGFR1 may be available as poor prognostic indicators in SCLC patients.
    International journal of clinical and experimental pathology 12/2013; 6(12):2846-54. · 1.89 Impact Factor
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    ABSTRACT: Breast cancers are heterogeneous and complex diseases, and subtypes of breast cancers may involve unique molecular mechanisms. The p16(INK4a) and p53 pathways are two of the major pathways involved in control of the cell cycle. They also play key roles in tumorigenesis. However, whether the roles of these pathways differ in the subtypes of breast cancer is unclear. Therefore, p16 and p53 expression were investigated in different breast cancer subtypes to ascertain their contributions to these cancers. A total of 400 cases of non-invasive ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), including the major molecular subtypes luminal-A, luminal-B, Her-2, and triple-negative subtypes, and 50 cases of normal controls were compared. Luminal-A cancers expressed the lowest level of p16 among the subtypes in DCIS, and the level of p16 expression was up-regulated in the luminal-A of IDC (P<0.008). Triple-negative breast cancers were characterized by a correlation of p53 overexpression with a high level of p16 expression. Luminal lesion types with high p16 expression in DCIS were found to be more likely to develop into aggressive breast cancers, possibly promoted by p53 dysfunction. Taken together, the present study suggest that p16 expression in luminal-A breast cancers is associated with their progression from DCIS to IDC, and both p53 and p16 expressions are important for the development of triple-negative breast cancers in DCIS and IDC.
    PLoS ONE 10/2013; 8(10):e76408. DOI:10.1371/journal.pone.0076408 · 3.23 Impact Factor
  • Qian Sun · Xianyu Zhang · Tong Liu · Xiaolong Liu · Jingshu Geng · Xiaohui He · Yang Liu · Da Pang ·
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    ABSTRACT: Aneuploidy is a characteristic of human cancers, and recent studies have suggested that defects of mitotic checkpoints play a role in carcinogenesis. Mitotic Arrest Deficient-Like 1 (MAD1L1), whose altered expression is associated with chromosomal instability, is a checkpoint gene. We examined MAD1L1 protein expression from 461 breast cancer tissues and patients' normal breast tissues by tissue microarray to study the correlation between the MAD1L1 expression and the clinicopathological features. MAD1L1 protein expression was significantly increased in the nuclei of cancer cells (28.4 %) compared with that in normal mammary cells (2.2 %), and was correlated with Her-2 status, cancer subtypes, p53 status, and age. High level of MAD1L1 expression in nuclei was associated with worse OS (p = 0.018). Furthermore, patients with high level of MAD1L1 expression (in nuclei) and undergone Taxol chemotherapy treatment have shorter overall survival than ones without Taxol treatment in this study (p = 0.026). In conclusion, our data demonstrated a significant correlation between nuclear expression of MAD1L1 protein and adverse prognosis in breast cancer. MAD1L1 might be used as a prognostic biomarker for breast cancer and expression of MAD1L1 in nuclei is also a predict biomarker of contraindication to pacilitaxel treatment in breast cancer.
    Breast Cancer Research and Treatment 07/2013; 140(2). DOI:10.1007/s10549-013-2633-8 · 3.94 Impact Factor
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    ABSTRACT: BACKGROUND: Inhibitor of growth 4 (ING4) has deserved attention as a tumor suppressor gene in many malignant tumors. In our study, we investigated ING4 immunoexpression in gastrointestinal stromal tumors (GISTs) and its prognostic value. METHOD: The expression of ING4 and Ki67 was investigated in 41 samples of various risk gastrointestinal stromal tumors by immunohistochemical technique. The associations of ING4 expression and clinicopathological parameters, and prognosis of the patients, were analyzed by multivariate Cox regression analysis. RESULTS: ING4 expression showed a decreased trend from lower-risk to high-risk gastrointestinal stromal tumors, and an opposite trend for Ki67 expression. In lower-risk tumors, it was found the expression level of ING4 was 78.95 % ± 27.90 % and that of Ki67 was 4.42 % ± 3.75 %. However, in high-risk tumors, the expression level of ING4 was 9.23 % ± 7.66 % and that of Ki67 was 18.50 % ± 9.09 %. There was a strongly negative correlation between the expression levels of ING4 and Ki67. A significant difference was observed in the expression of ING4 between invasion and non-invasion (p < 0.001). The expression of ING4 was markedly correlated with tumor size (p < 0.001), mitotic index (p < 0.001), tumor necrosis (p = 0.021), invasion (p < 0.001), recurrence and metastasis (p = 0.021), and mortality (p < 0.001). CONCLUSION: The low expression level of ING4 protein was correlated with high-risk GISTs. ING4 might be involved in the progression of GISTs and inhibit its invasion. ING4 might be one of the prognostic indicators in GISTs.
    Gastric Cancer 03/2013; 17(1). DOI:10.1007/s10120-013-0248-8 · 3.72 Impact Factor
  • Cong Li · Jianping Cai · Jingshu Geng · Yinghong Li · Zhenyu Wang · Rui Li ·
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    ABSTRACT: In this study, we purified a homogeneous polysaccharide (PGPW1) from the root of Panax ginseng. Its molecular weight was estimated to be 3.5×10(5)Da by high performance liquid chromatography (HPLC) and Gas chromatography (GC) analysis identified that PGPW1 contained Glc, Gal, Man and Ara in the molar ratio of 3.3:1.2:0.5:1.1. Furthermore the antitumor potential of PGPW1 on human bladder T24 cells was evaluated in vitro by MTT, lactate dehydrogenase (LDH), wound scratch and transwell motility assays. PGPW1 dose-dependently displayed potent anti-proliferation and anti-metastatic activities. Moreover the modulating effect of PGPW1 on the binding of (3)H-NMS to M3 muscarinic receptors on the surface of T24 cells was evaluated. In muscarinic receptor binding assay, the attenuated expression of M3 muscarinic receptor on the surface of T24 cells by PGPW1 would contribute to its antitumor functions. All the data indicated the potential of its clinical application for the prevention and treatment of bladder cancer metastasis.
    International journal of biological macromolecules 06/2012; 51(5):968-73. DOI:10.1016/j.ijbiomac.2012.06.031 · 2.86 Impact Factor
  • Shuhuai Wang · Xinmei Kang · Shouqiang Cao · Hui Cheng · Di Wang · Jingshu Geng ·
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    ABSTRACT: Background and aims: The nuclear factor of the activated T cell (NFAT) family was primarily recognized for its central role in T lymphocyte activation. Recent evidence showed that NFAT isoforms participate in the regulation of genes related to cell proliferation and differentiation in epithelial malignancies. Here, we investigated the expression and activation of the calcineurin/NFAT transcription pathway and its role in hepatocellular carcinoma (HCC) proliferation. Methods: Expression of NFATc1 and calcineurin proteins was examined by immunohistochemical analyses in 76 human HCC samples. The cellular NFAT activation and distribution in HepG2 cells were analyzed by immunofluorescence and western blot analyses. After NFATc1 expression was knocked down by NFATc1-specific siRNA, we analyzed its implications in cell cycle progression and growth by MTT and flow cytometry. The impact of calcineurin/NFAT signaling on protein expression of c-myc and cox-2 were performed by western blot analyses. Results: NFATc1 is significantly overexpressed in HCC. The regulation of calcineurin activity by ionomycin or cyclosporin A caused rapid nuclear import or export of NFATc1 in HepG2 cells. NFATc1 knock-down led to a significant reduction in proliferation rates and cell cycle arrest at G1 phase. The expression of c-myc and cox-2 was decreased in the NFATc1 knock-down HepG2 cells. Ionomycin increased c-myc and cox-2 expression in HepG2 cells, but not in siNFATc1 HepG2 cells. Conclusion: The calcineurin/NFATc1 signal is overexpressed and active in HCC. It may enhance the proliferative potential of HepG2 cells through transcriptional activation of the c-myc and cox-2 oncogenes.
    Digestive Diseases and Sciences 06/2012; 57(12). DOI:10.1007/s10620-012-2255-8 · 2.61 Impact Factor
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    ABSTRACT: To correlate astrocyte elevated gene-1 (AEG-1) expression with the clinicopathological features and outcome of patients with stages III-IV ovarian serous carcinoma, and to clinically assess the involvement of AEG-1 in acquired cisplatin resistance. The frequency and intensity of immunohistochemical AEG-1 expression increased in a step-wise fashion from normal to chemosensitive to chemoresistant tissues. These observations were confirmed by Western blot analysis. AEG-1 expression level was correlated with lymph nodal metastasis, histological differentiation, residual tumour size and response to primary chemotherapy. Five-year progression-free survival (PFS) and overall survival (OS) rates were lower in the high-expression group than that in the low-expression group. AEG-1 overexpression was an independent but poor prognostic factor in the OS and PFS of these patients, as determined by multivariate Cox regression analysis. Multivariate logistic regression analysis revealed that the presence of cisplatin-based chemoresistance was significantly associated with expression level of AEG-1 and the degree of residual disease (P = 0.0001 and P = 0.0027, respectively). Our findings indicate that tumour AEG-1 overexpression is associated with poor prognosis and cisplatin resistance in advanced serous ovarian cancer.
    Histopathology 02/2012; 60(6):953-63. DOI:10.1111/j.1365-2559.2012.04182.x · 3.45 Impact Factor
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    ABSTRACT: Human non-small cell lung cancer (NSCLC) is one of the most common malignancies in the modern world. Its recurrence is mainly due to its ability to invade and metastasize. However, the precise mechanism for tumor development and metastasis is still not fully understood. To shed light on the development of lung cancer, the human giant cell lung carcinoma cell lines 95D with high metastatic potential and 95C with low metastatic potential were selected in this study. The 2 cell lines originated from the same parental cell and share a similar genetic background. In the current study, we identified 3 differentially expressed proteins in 95C and 95D cell lines, namely, PAI-RBP1, C1orf142, and COTL1, by using 2-dimensional electrophoresis proteomics analysis. We found that PAI-RBP1 and C1orf142 expression levels were higher in 95D than in 95C cells, whereas COTL1 expression level was lower in 95D when compared to 95C cells. We also confirmed these results by reverse transcription-polymerase chain reaction and immunoblotting analyses. The messenger RNA and protein levels of PAI-RBP1 and C1orf142 were much higher in 95D than in 95C cells, and COTL1 expression level was lower in 95D than in 95C cells. The PAI-RBP1 expression was assessed by immunohistochemistry in 70 NSCLC and 7 normal lung tissue samples from patients. PAI-RBP1 expression level was higher in tumor tissues (positive staining in 87.1% of cases [61/70]) than in normal tissues (positive staining in 14.3% of cases [1/7]). In conclusion, by studying protein expression in NSCLC cell lines with high and low metastasis as well as in human lung cancer tissues, we have identified 3 proteins, namely, PAI-RBP1, C1orf142, and COTL1, which were differentially expressed in NSCLC cell lines with different metastatic potential. In addition, we also found that PAI-RBP1 might contribute to NSCLC development.
    Journal of Investigative Medicine 02/2012; 60(4):689-94. · 1.69 Impact Factor
  • Lijuan Yu · Mohan Tian · Xuan Gao · Dalong Wang · Yu Qin · Jingshu Geng ·
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    ABSTRACT: The aim of this study was to analyze the morphologic and functional features of metastatic lymph nodes of colorectal carcinoma on (18)F-fluorodeoxyglucose positron emission tomographic (PET)/computed tomographic (CT) images and correlate these with pathologic results to explore the best diagnostic performance. Sixty-eight patients without any previous treatment underwent (18)F-fluorodeoxyglucose PET/CT examinations and subsequent operations. All lymph nodes were evaluated by recording short diameter and maximum standardized uptake value (SUVmax) on axial images and were carefully verified on the surgically resected specimens. The radiologic diagnostic efficacies on the basis of different diagnostic criteria were compared and evaluated with pathologic results. There was a significant difference for SUVmax between metastatic and benign juxtaintestinal lymph nodes (F = 96.836, P = .000) and a correlation between size and SUVmax in metastatic juxtaintestinal lymph nodes (r = 0.352, P = .038). Diagnosing according to short diameter ≥ 10 mm and SUVmax ≥ 2.5, the sensitivity, specificity, positivity prediction value (PPV), and negative prediction value (NPV) were 10.00%, 98.26%, 66.67%, and 75.84% and 82.50%, 90.43%, 75.00%, and 93.69%, respectively. Considered together, the sensitivity, specificity, PPV, and NPV were 10.00%, 99.13%, 80.00%, and 76.00%, respectively. Receiver-operating characteristic curves showed that the best cutoff values for SUVmax and short diameter were 2.0 and 4.85 mm, respectively; the corresponding sensitivity, specificity, PPV, and NPV, were 91.43%, 87.83%, 69.57%, and 97.12% and 85.71%, 60.87%, 40.00%, and 98.2%, respectively. Considered together, the sensitivity, specificity, PPV, and NPV were 95.00%, 86.96%, 71.70%, and 98.04%, respectively. Fluorine-18-fluorodeoxyglucose uptake was a more reliable indicator in diagnosing malignant juxtaintestinal lymph node of colorectal carcinoma. The optimal diagnostic efficacy could be reached by considering morphologic and functional features together.
    Academic radiology 01/2012; 19(4):427-33. DOI:10.1016/j.acra.2011.12.007 · 1.75 Impact Factor
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    ABSTRACT: Lung cancer is a leading cause of cancer-related death, about 40% human non-small cell lung cancer (NSCLC) patients showed lymph node involvements. However, the precise mechanism for the metastasis is still not fully understood. This study was to analyze the potential molecular mechanism for lung cancer metastasis. In the current study, proteomics analysis by two-dimensional electrophoresis (2-DE) was performed first to identify the differentially expressed protein between the higher metastasis lung adenocarcinoma cell line Anip973 and the lower metastasis lung adenocarcinoma cell line AGZY83-a. We confirmed the result by RT-PCR, immunoblotting and immunocytochemistry analyses in these two cell lines. Then we examined the expression of the differentially expressed protein in tumor tissues of NSCLC patients by immunoblotting and immunohistochemistry analyses. Using 2-DE analysis, we have identified DJ-1 was expressed higher in the higher metastasis Anip973 compared to the parental cell line AGZY83-a, that was confirmed by RT-PCR, immunoblotting and immunocytochemistry analyses. In NSCLC patients' tumor tissues study, immunoblotting data showed that, DJ-1 expression level was significantly higher in 72.2% (13/18) of NSCLC tissue samples compared to that in paired normal lung tissues (P = 0.044). Immunohistochemistry analysis demonstrated increased DJ-1 expression in 85 NSCLC tumor tissue samples compared with 7 normal lung tissue samples (P = 0.044). DJ-1 expression was also found to be significantly correlated with cancer lymphatic metastasis (P = 0.039). DJ-1 might contribute to the metastasis of NSCLC.
    Molecular Biology Reports 06/2011; 39(3):2697-703. DOI:10.1007/s11033-011-1024-7 · 2.02 Impact Factor
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    ABSTRACT: Despite advances in chemotherapy and cytoreductive surgery, ovarian cancer remains the most lethal gynecological malignancy with a 5-year survival rate of 25% to 30% in advanced stage disease. Our purpose is to evaluate whether astrocyte elevated gene-1 (AEG-1) is a novel predictor of peritoneal dissemination and lymph node metastasis in epithelial ovarian cancer (EOC), which was not previously studied by others. Through immunohistochemical and Western blot analysis, AEG-1 expression was evaluated in 25 normal ovarian and 157 EOC specimens. The relationship between AEG-1 expression and EOC metastasis was determined by univariate and multivariate analyses. Western blotting analysis revealed that AEG-1 was overexpressed in metastatic tissues from patients with ovarian cancers. Immunohistochemistry results showed that 83 (95.4%) presented peritoneal dissemination; 41 (47.1%) had lymph node metastasis among 87 patients with AEG-1 overexpression. Univariate and multivariate logistic regression analyses demonstrated that AEG-1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. We further found that the positive and specificity predictive value of AEG-1 staining were better for peritoneal metastasis, whereas the negative and sensitivity predictive value of AEG-1 staining were better for lymph node metastasis. The odds ratio of high-to-low expression for peritoneal dissemination was 8.541 (95% confidence interval, 2.561-37.461), and that for lymph node metastasis was 9.581 (95% confidence interval, 2.613-23.214). The present findings indicate that AEG-1 is overexpressed in a great portion of EOC patients with peritoneal dissemination and/or lymph node metastasis and may be clinically useful for predicting metastasis in EOC. Our findings might provide some benefits for metastatic EOC patients in the clinic.
    International Journal of Gynecological Cancer 05/2011; 21(4):602-8. DOI:10.1097/IGC.0b013e3182145561 · 1.95 Impact Factor
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    ABSTRACT: Previously, we identified 3 overlapping regions showing loss of heterozygosity (LOH, R(1)-R(3) from 11 to 30 cM) on chromosome 17 in 45 primary gastric cancers (GCs). The data indicated the presence of tumor suppressor genes (TSGs) on chromosome 17 involved in GC. Among the putative TSGs in these regions, HIC1 (in SR(1)) and TOB1 (in SR(3)) remain to be examined in GC. By immunohistochemistry (IHC), methylation-specific PCR (MSP) and western blot, we evaluated the expression and regulation status for HIC1 and TOB1 protein in GC. We narrowed down the deletion intervals on chromosome 17 and defined five smaller LOH subregions, SR(1)-SR(5) (0.54 to 3.42 cM), in GC. We found that HIC1 had downregulated expression in 86% (91/106) and was methylated in 87% (26/30) of primary GCs. Of the primary GCs showing downregulation of HIC1 protein, 75% (18/24) had methylated HIC1 gene. TOB1 was either absent or expressed at reduced levels in 75% (73/97) of the GC samples. In addition, a general reduction was found in total and the ratio of unphosphorylated to phosphorylated TOB1 protein levels in the differentiated GC cell lines. Further analysis revealed significant simultaneous downregulation of both HIC1 and TOB1 protein in GC tissue microarray samples (67%, 52/78) and in primary GCs (65%, 11/17). These results indicate that silencing of HIC1 and TOB1 expression is a common occurrence in GC and may contribute to the development and progression of the disease.
    Moleculer Cells 04/2011; 32(1):47-55. DOI:10.1007/s10059-011-2316-4 · 2.09 Impact Factor
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    ABSTRACT: Our study is to examine astrocyte-elevated gene-1 (AEG-1) expression in triple-negative breast cancer and to determine whether it is associated with vascular endothelial growth factor (VEGF), microvessel density (MVD), clinicopathological parameters and poor survival. Specimens from 125 patients with triple-negative breast cancers were investigated by immunohistochemistry for MVD, AEG-1 and VEGF expression. Correlations between the expression of AEG-1, VEGF, MVD, and various clinicopathological factors including survival status were studied. AEG-1 and VEGF were highly expressed in 56.8% and 52.8% of triple-negative breast cancer patients, respectively. The intensity of AEG-1 was gradually up-regulated from VEGF-MVD-low, VEGF-high, or MVD-high to VEGF-MVD-high tissues using Western blot analysis. Statistically significant correlation was found among AEG-1 and VEGF, and MVD. Moreover, AEG-1 expression was correlated with clinical stage, lymphatic venous invasion, lymph nodal metastasis, tumor size, Ki67, and recurrence. Patients with AEG-1 high-expression showed far lower disease-free survival (DFS) and overall survival (OS) rates than those with AEG-1 low-expression. For VEGF and MVD, there were similar results in these patients. Only AEG-1 expression and tumor size were independent prognostic factors for both DFS and OS by multivariate analysis. However, the prognostic impact of tumor size was not as strong as that of AEG-1. AEG-1 expression may be related with tumor angiogenesis and progression and is a valuable prognostic factor in patients with triple-negative breast cancer.
    Journal of Surgical Oncology 02/2011; 103(2):184-92. DOI:10.1002/jso.21788 · 3.24 Impact Factor
  • Hongtao Song · Cong Li · Renbo Lu · Yuan Zhang · Jingshu Geng ·
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    ABSTRACT: To assess the expression of astrocyte elevated gene-1 (AEG-1) in different endometrial specimens and to investigate its relationship with clinicopathological features and its impact on patient outcome. By Western blot analysis, we investigated AEG-1 expression in paired endometrial tissues and adjacent nontumor tissues of the same patients (n = 4). Immunohistochemistry analysis was used to determine the expression levels of AEG-1 protein in 35 normal endometrium, 40 atypical endometrial hyperplasia, and 174 endometrial cancers. The correlation between AEG-1 expression and various clinicopathological characteristics of endometrial cancer patients was analyzed. Western blot analysis showed that AEG-1 expression levels were up-regulated in all 4 human primary endometrial cancer tissues compared with their matched adjacent noncancerous tissues. The frequent and strong expression of AEG-1 was gradually elevated in normal endometrial tissue, atypical hyperplasia, and endometrial cancers (P < 0.001). Although AEG-1 staining mainly emerged in the cytoplasm, a nuclear distribution was observed in both invasive and advanced endometrial cancer cells. The Ki67 (a proliferation marker) was frequently expressed in the high AEG-1-expressed area, whereas areas with low AEG-1 levels showed weak Ki67 expression. Astrocyte elevated gene-1 overexpression was positively correlated with the International Federation of Gynecology and Obstetrics stage, depth of myometrial invasion, lymph node metastasis, lymph vascular space invasion, and recurrence but not with age or histological type. Patients with high AEG-1 expression had significantly poor overall survival and disease-free survival compared with patients with AEG-1 low expression (both P < 0.001). Multivariate Cox proportional hazards regression demonstrated that high AEG-1 expression was an independent prognostic factor for both the overall survival and disease-free survival of patients with endometrial cancer (P = 0.002 and P = 0.004, respectively). Astrocyte elevated gene-1 overexpression may be associated with carcinogenesis and tumor progression in endometrial cancer. Moreover, it may be a new prognostic marker or a target for improving the treatment efficiency of patients with endometrial cancer.
    International Journal of Gynecological Cancer 10/2010; 20(7):1188-96. · 1.95 Impact Factor