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Yun-Xia DU,
Lian-Hai Zhang,
Xiao-Hong Wang,
Xiao-Fang Xing,
Xiao-Jing Cheng, Hong DU,
Ying Hu,
Ying-Ai Li,
Yu-Bing Zhu,
Yong-Ning Jia,
Yi Lin,
Jia-Fu Ji
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ABSTRACT: To explore the expression of CCAAT/enhancer binding protein beta (CEBPB)in gastric carcinoma tissues and its association with clinicopathological features and prognosis.
CEBPB protein expression level was detected by immunohistochemistry method in resected gastric carcinomas and adjacent gastric mucosa tissues(n=81), and its association with clinicopathological features and prognosis was analyzed.
The immunohistochemical staining of CEBPB was predominantly in the nucleus with some cytoplasmic staining. As a result, 16%(13/81) of the gastric carcinomas were stained positively, whereas there was hardly positive expression in adjacent gastric mucosa tissues. There was a significant association between the expression of CEBPB and distant metastasis on univariate analysis(P<0.05). The median survival time in patients with positive CEBPB expression was significantly lower than those with negative CEBPB expression(19.4 months vs. 45.2 months, P=0.024). Multivariable analysis showed that CEBPB was independently associated with prognosis(HR=2.544, 95%CI:1.154-5.610, P=0.021).
Up-regulation of CEBPB suggests poor prognosis in patients with gastric cancer.
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 02/2013; 16(2):179-82.
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Biao Fan,
Lian-Hai Zhang,
Yong-Ning Jia,
Xi-Yao Zhong,
Yi-Qiang Liu,
Xiao-Jing Cheng,
Xiao-Hong Wang,
Xiao-Fang Xing,
Ying Hu,
Ying-Ai Li, Hong Du,
Wei Zhao,
Zhao-Jian Niu,
Ai-Ping Lu,
Ji-You Li,
Jia-Fu Ji
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ABSTRACT: S100A9 was originally discovered as a factor secreted by inflammatory cells. Recently, S100A9 was found to be associated with several human malignancies. The purpose of this study is to investigate S100A9 expression in gastric cancer and explore its role in cancer progression.
S100A9 expression in gastric tissue samples from 177 gastric cancer patients was assessed by immunohistochemistry. The expression of its dimerization partner S100A8 and the S100A8/A9 heterodimer were also assessed by the same method. The effect of exogenous S100A9 on motility of gastric cancer cells AGS and BGC-823 was then investigated.
S100A9 was specifically expressed by inflammatory cells such as macrophages and neutrophils in human gastric cancer and gastritis tissues. Statistical analysis showed that a high S100A9 cell count (> = 200) per 200x magnification microscopic field in cancer tissues was predictive of early stage gastric cancer. High S100A9-positive cell count was negatively correlated with lymph node metastasis (P = 0.009) and tumor invasion (P = 0.011). S100A9 was identified as an independent prognostic predictor of overall survival of patients with gastric cancer (P = 0.04). Patients with high S100A9 cell count were with favorable prognosis (P = 0.021). Further investigation found that S100A8 distribution in human gastric cancer tissues was similar to S100A9. However, the number of S100A8-positive cells did not positively correlate with patient survival. The inflammatory cells infiltrating cancer were S100A8/A9 negative, while those in gastritis were positive. Furthermore, exogenous S100A9 protein inhibited migration and invasion of gastric cancer cells.
Our results suggested S100A9-positive inflammatory cells in gastric cancer tissues are associated with early stage of gastric cancer and good prognosis.
BMC Cancer 07/2012; 12:316. · 3.01 Impact Factor
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Yi Lin,
Lian-Hai Zhang,
Xiao-Hong Wang,
Xiao-Fang Xing,
Xiao-Jing Cheng,
Bin Dong,
Ying Hu, Hong Du,
Ying-Ai Li,
Yu-Bing Zhu,
Ning Ding,
Yun-Xia Du,
Ji-You Li,
Jia-Fu Ji
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ABSTRACT: BACKGROUND AND OBJECTIVES: Protein tyrosine kinase 7 (PTK7) plays important functions in several cancer types but its expression in gastric cancer remains unknown. This study was designed to investigate PTK7 expression in gastric cancer. METHODS: PTK7 expression was assessed by immunohistochemistry in 201 gastric cancer patients. The relationship between PTK7 expression and clinicopathological features and patients prognosis were statistically analyzed. RESULTS: PTK7 expression was detected in 56.72% (114 of 201) of gastric cancer patients. The immunostaining was predominantly localized in the cytoplasm. The statistical analyses showed that PTK7 expression was more frequently detected in patients with well-differentiated tumors (P = 0.001). Furthermore, PTK7 expression was significantly related to the favorable overall survival (OS; P = 0.012) and disease-free survival (DFS; P = 0.009). Multivariate Cox regression analyses revealed that PTK7 expression was an independent prognostic factor for both favorable OS (P = 0.028) and DFS (P = 0.012). CONCLUSION: Our findings demonstrate that PTK7 can serve as a novel prognostic biomarker for gastric cancer patients. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.
Journal of Surgical Oncology 05/2012; · 2.10 Impact Factor
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Yu-bing Zhu,
Shao-hua Ge,
Lian-hai Zhang,
Xiao-hong Wang,
Xiao-fang Xing, Hong DU,
Ying Hu,
Ying-ai Li,
Yong-ning Jia,
Yi Lin,
Biao Fan,
Jia-fu Ji
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ABSTRACT: To investigate the clinical value of tumor markers CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of patients with gastric cancer.
One hundred and sixty gastric cancer patients who had received treatment from 2002 to 2007 at the Beijing Cancer Hospital were retrospectively analyzed. Blood samples were taken from patients upon admission to the hospital, and CEA, CA19-9, CA72-4, CA242 levels were detected. Statistical analysis was performed to identify the clinical value of these tumor markers in diagnosis and prognosis.
On initial diagnosis, the positive rates of CEA, CA19-9, CA72-4 and CA242 were 37.7%, 26.7%, 37.6% and 21.3%, respectively, and the positive rate of combined detection was 62.9%. CEA was more frequently positive in patients with lymph node metastasis(P=0.029); CA72-4 was more frequently positive in patients with vascular involvement and advanced stage(P=0.039, P=0.011). Multivaraite analysis showed that CA72-4 was an independent prognostic factor(P=0.012). Patients with positive CA72-4 carried a 2.147-fold increased risk of death than those with negative CA72-4. Kaplan-Meier analysis showed that patients with positive CA19-9 or positive CA72-4 had worse survival than those with negative CA19-9 or CA72-4(P=0.006, P=0.002).
Tumor markers including CEA, CA19-9, CA72-4 and CA242 have clinical significance and prognostic value in patients with gastric cancer. Combined detection of four tumor markers can increase the positive rate. CA72-4 is an independent prognostic factor. CA19-9 and CA72-4 are associated with the prognosis of patients with gastric cancer.
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 02/2012; 15(2):161-4.
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Xiao-Fang Xing,
Hong Li,
Xi-Yao Zhong,
Lian-Hai Zhang,
Xiao-Hong Wang,
Yi-Qiang Liu,
Shu-Qin Jia,
Tao Shi,
Zhao-Jian Niu,
Yong Peng, Hong Du,
Gui-Guo Zhang,
Ying Hu,
Ai-Ping Lu,
Ji-You Li,
She Chen,
Jia-Fu Ji
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ABSTRACT: The secreted phospholipase A2 type IIA (PLA2G2A) gene has been identified as a modifier of intestinal adenoma multiplicity in Apc(Min/+) mice. The aim of the present study was to analyse the clinical significance of PLA2G2A expression in human gastric cancer.
Using immunohistochemistry, cytoplasmic immunoreactivity of PLA2G2A was observed in 27% (40 of 149) of gastric cancer tissues compared with negative staining in normal mucosa. The PLA2G2A expression rate in well-differentiated carcinoma was elevated significantly compared with that in poorly differentiated carcinoma (46% versus 19%, P = 0.001). Statistical analysis also revealed that PLA2G2A expression correlated negatively with depth of mural invasion, lymph node metastasis and tumour-node-metastasis (TNM) stage (P < 0.05). Patients with positive PLA2G2A expression showed higher 5-year overall survival than those with negative expression (P = 0.0004). In intestinal metaplasia, PLA2G2A was found to be abundant in Paneth cells. The coexistence of PLA2G2A and lysozyme was observed in Paneth cell-rich gastric cancer (P < 0.0001).
PLA2G2A may predict survival and might be a potential biomarker for early detection and individualized therapy.
Histopathology 08/2011; 59(2):198-206. · 3.08 Impact Factor
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ABSTRACT: The aim of this study was to detect metastasis-associated in colon cancer-1 (MACC1) expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival.
The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records.
The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa (P<0.001). MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma (P=0.032). Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 (P=0.057). Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer (P=0.002), but P53 expression was not associated with MACC1 expression.
MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.
Chinese Journal of Cancer Research 06/2011; 23(2):153-159. · 0.18 Impact Factor
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Xiao-Hong Wang,
Lian-Hai Zhang,
Xi-Yao Zhong,
Xiao-Fang Xing,
Yi-Qiang Liu,
Zhao-Jian Niu,
Yong Peng, Hong Du,
Gui-Guo Zhang,
Ying Hu,
Ni Liu,
Yu-Bing Zhu,
Shao-Hua Ge,
Wei Zhao,
Ai-Ping Lu,
Ji-You Li,
Jia-Fu Ji
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ABSTRACT: S100A6 has been implicated in a variety of biological functions as well as tumorigenesis. In this study, we investigated the expression status of S100A6 in relation to the clinicopathological features and prognosis of patients with gastric cancer and further explored a possible association of its expression with epigenetic regulation. S100A6 expression was remarkably increased in 67.5% of gastric cancer tissues as compared with matched noncancerous tissues. Statistical analysis demonstrated a clear correlation between high S100A6 expression and various clinicopathological features, such as depth of wall invasion, positive lymph node involvement, liver metastasis, vascular invasion, and tumor-node metastasis stage (P < 0.05 in all cases), as well as revealed that S100A6 is an independent prognostic predictor (P = 0.026) significantly related to poor prognosis (P = 0.0004). Further exploration found an inverse relationship between S100A6 expression and the methylation status of the seventh and eighth CpG sites in the promoter/first exon and the second to fifth sites in the second exon/second intron. In addition, the level of histone H3 acetylation was found to be significantly higher in S100A6-expressing cancer cells. After 5-azacytidine or trichostatin A treatment, S100A6 expression was clearly increased in S100A6 low-expressing cells. In conclusion, our results suggested that S100A6 plays an important role in the progression of gastric cancer, affecting patient prognosis, and is up-regulated by epigenetic regulation.
American Journal Of Pathology 08/2010; 177(2):586-97. · 4.89 Impact Factor
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ABSTRACT: The endothelial cell-specific molecule-1 (ESM-1) gene is involved in various biological events. This study was designed to clarify its clinical significance and explore its biological behavior in gastric cancer (GC).
ESM-1 mRNA expression was evaluated by real-time PCR in GC (n = 34) and matched adjacent normal tissues (n = 14). The expression of ESM-1 protein was investigated by immunohistochemistry in GC (n = 159) and matched normal tissues (n = 40), and its correlation with the clinicopathological features and overall survival of patients was analyzed. Microvessel density (MVD) in GC was assessed by anti-CD34 and the pattern of ESM-1 expression in tumor-related vascular was evaluated. The effect of ESM-1 promotion of proliferation in the GC MKN28 cell line and human microvascular endothelial cell line HMEC-1 were tested using the MTT assay.
ESM-1 mRNA was significantly overexpressed in GC compared with adjacent noncarcinoma controls (P < 0.01). ESM-1 protein was predominantly expressed in GC. ESM-1 expression was associated with distant metastasis and Borrmann type IV (P < 0.05) and was strongly associated with vascular invasion (P = 0.0057). Patients with ESM-1 expression showed lower 5-year survival rate (P = 0.0339). Multivariate analysis revealed that ESM-1 was an independent prognostic factor. In GC, CD34-MVD of GC vessels positively expressing ESM-1 was higher than that of GC with negative vessels expression of ESM-1 (P < 0.05). Besides, ESM-1 antibody dose-dependently impaired MKN28 and HMEC-1 growth.
ESM-1 is overexpressed in GC and can serve as a tumor biomarker to predict survival of GC patients, and it might promote tumor angiogenesis and growth in GC and, hence, may represent a potential therapeutic target.
Annals of Surgical Oncology 04/2010; 17(10):2628-39. · 4.17 Impact Factor
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ABSTRACT: The objective of this study was to identify differentially expressed proteins of advanced gastric cancer from patients with different prognosis using NanoLC-MS/MS (LTQ) (nanoflow liquid chromatography system interfaced with a linear ion trap LTQ mass spectrometer).
Eight gastric cancer patients with relatively early TNM stage and survival time >34 months were identified as good survival (group G), while the other eight with late stage and survival time <15 months as poor survival (group P). The total protein of the tissue samples from each group was extracted and pooled together respectively. The resulting two protein mixtures were trypsin-digested and analyzed using NanoLC-MS/MS (LTQ). Database searches were done against NCBI non-redundant database and SWISS-PROT database and the identified proteins were classified through an online Web Gene Ontology Annotation Plot tool. Immunohistochemistry was used to verify candidate prognosis-related proteins.
There were 284 and 213 proteins identified for group G and group P respectively. And 117 proteins were detected exclusively in group G and 46 proteins exclusively in group P. These protein markers function in calcium ion signaling pathway, cellular metabolism, cytoskeleton formation, stress reaction, etc. Among those, the down-regulated expression of S100P was verified to claim a poor clinical outcome of gastric cancer patients (P = 0.0375).
The MS-based proteomics approach is efficient in identifying differentially expressed proteins in relation to prognosis of advanced gastric cancer patients. These differentially expressed proteins could be potential prognosis-related cancer markers and deserve further validation and functional study.
Journal of Cancer Research and Clinical Oncology 10/2008; 135(3):403-11. · 2.56 Impact Factor
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Qing-Feng Zheng,
Bin Dong,
Yu Sun, Hong DU,
Hong-Chao Xiong,
Nan Wu,
Jin-Feng Chen,
Lu Sun,
Jie Ao,
Ji-You Li,
Jia-Fu Ji,
Yue Yang
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ABSTRACT: To investigate the expression and significance of TR4-associated Protein (TRA16) in human non-small cell lung cancer (NSCLC) tissues.
Immunohistochemistry (IHC) and tissue array were employed to investigate the expression of TRA16 in NSCLC cases of different pathological types, benign lung lesions and normal lung tissues.
The abundant expression of TRA16 was observed in nucleus and/or cytoplasm of NSCLC cells with a positive expression rate of 88.64%, whereas normal lung tissue and benign lung tumor rarely expressed TRA16 protein. The expression of TRA16 showed no apparent difference at pathotypes and differentiation levels.
In this study we demonstrated an abnormal overexpression of TRA16 in NSCLC tissues. The unique expression pattern of TRA16 indicated its probable role in tumorigenesis and progression, supporting the development of TRA16 as a novel potential NSCLC marker.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 11/2007; 39(5):472-5.
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ABSTRACT: To investigate the intracellular localization of S100A4 in gastric carcinoma cells and the relationship between S100A4 expression status and lymph node metastasis of gastric carcinoma.
Western blotting analysis was performed to locate the expression of S100A4 protein in sub-fraction components of frozen tissues. S100A4 protein expression was also determined by immunohistochemical method in 131 samples of gastric cancer and 20 samples of matched metastatic lymph nodes.
Thirty-two of 131 (24.4%) gastric carcinoma showed positive S100A4 nuclear expression and 50/131 (38.2%) carcinoma showed positive cytoplasmic expression. In 32 samples with positive S100A4 nuclear expression, 30 (93.8%) carcinomas had positive lymph node metastases. S100A4 nuclear expression level was higher in gastric carcinoma with lymph node metastasis (29.1%) than that without lymph node metastasis (7.1%) (P=0.016).
Nuclear expression of S100A4 is associated with lymph node metastasis of gastric carcinoma.
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 10/2007; 10(5):454-7.
