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EFFECTS OF MUTATION AND EXPRESSION OF PTEN GENEmRNA ON TUMORIGENESIS AND PROGRESSION OFEPITHELIAL OVARIAN CANCER

Chinese Medical Sciences Journal 2004年第1期19卷 25-30页

作者：陈颖郑华川杨雪飞孙丽梅辛彦 Shenyang Hospital of Obstetrics and Gynecology The Fourth laboratory Cancer Institute the First Affiliated Hospital ofChina Medical University

Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary(n = 5), ovarian cyst (n =5), ovarian borderline tumor (n = 9), epithelial ovarian cancer(n = 60), and ovarian cancer cell line (n = 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clini-copathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5(7.1%)cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst(P clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05=. Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.

关键词： ovarian neoplasms PTEN gene mutation gene expression

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High expression level of EDIL3 in HCC predicts poor prognosis of HCC patients

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World Journal of Gastroenterology 2010年第36期16卷 4611-4615页

作者： Jian-Cong Sun,Xiao-Ting Liang,Ke Pan,Hui Wang,Jing-Jing Zhao,Jian-Jun Li,Hai-Qing Ma,Yi-Bing Chen,Jian-Chuan Xia,State Key laboratory of Oncology in South China,Cancer Center,Sun Yat-Sen University,Guangzhou 510060,Guangdong Province,China State Key laboratory of Oncology in Southern China Cancer Center Sun Yat-Sen University Guangzhou 510060 Guangdong Province China.

AIM:To determine the role of epidermal growth factor-like repeats and discoidin I-like domains 3(EDIL3)in pathogenesis of hepatocellular carcinoma(HCC)by investigating the EDIL3 expression in HCC and its prognostic value for ***:EDIL3 expression was detected in 101 HCC surgical tissue samples with immunohistochemistry method,and its relation with clinicopathologic features and prognosis of HCC patients was ***:EDIL3 was highly expressed in 48.5%of the HCC *** the EDIL3 expression level did not correlate with any clinicopathological parameters,KaplanMeier survival analysis showed that high expression level of EDIL3 resulted in a significantly poor prognosis of HCC patients(log-rank test,P=0.010).Multivariate Cox's analysis showed that the EDIL3 expression level was a significant and independent prognostic parameter for the overall survival rate of HCC patients(hazard ratio=1.978,95%confidence interval =1.139-3.435,P=0.015).CONCLUSION:High expression level of EDIL3 pre-dicts poor prognosis of HCC ***3 may be a potential target of antiangiogenic therapy for HCC.

关键词： Epidermal growth factor-like repeats and discoidin I-like domains 3 Hepatocellular carcinoma Prognosis Angiogenesis

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BAP31 is frequently overexpressed in patients with primary colorectal cancer and correlates with better prognosis

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Chinese Science Bulletin 2011年第23期56卷 2444-2449页

作者： DONG LingYi JIANG KeWei ZHANG YanBin ZHANG Hui ZHUO HongQing CUI ZhiRong YE YingJiang WANG Shan Department of Gastroenterological Surgery Surgical Oncology Laboratory Peking University People's Hospital Peking University Beijing100044 China

We previously showed that B cell receptor associated protein 31(BAP31) was significantly upregulated in colorectal cancer compared with normal mucosa epithelia. However, its expression pattern and pathological role in colorectal cancer are not clearly understood. In this study, we investigated whether the expression of BAP31 was associated with the clinicopathological parameters of colorectal cancer. The expression pattern of BAP31 was detected by immunohistochemistry on a tissue microarray in both primary tumor and paired distant normal mucosa samples from 120 consecutive colorectal cancer patients. Furthermore, BAP31 protein expression was also determined in twenty colorectal adenomas and eight liver metastasis samples. There was positive expression of BAP31 in 64.17% of primary tumors and 6.67% in distant normal mucosa (P=0.000). Negative expression of BAP31 was correlated with distant metastasis (P=0.036) and lower tumor differentiation grade (P=0.001). Patients with BAP31-negative expression showed significantly lower overall survival rate (P=0.003) compared to patients with BAP31-positive expression. Our results demonstrate that BAP31 may serve as a candidate prognostic marker in colorectal cancer and negative BAP31 expression may lead to more aggressive invasion of colorectal cancer.

关键词：患者结直肠癌过度表达预后原发性受体相关蛋白免疫组化检测粘膜上皮

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Relationship between autophagy and perineural invasion, clinicopathological features, and prognosis in pancreatic cancer

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World Journal of Gastroenterology 2017年第40期23卷 7232-7241页

作者： Yan-Hui Yang Jiang-Bo Liu Yang Gui Liang-Liang Lei Shui-Jun Zhang Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Zhengzhou University Department of Hepatobiliary Surgery First Affiliated Hospital College of Clinical Medicine Henan University of Science and Technology Department of General Surgery First Affiliated Hospital College of Clinical Medicine Henan University of Science and Technology Henan Key laboratory of Digestive Organ Transplantation Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities Zhengzhou Key Laboratory of Hepatobiliary Pancreatic Diseases and Organ Transplantation

AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubuleassociated protein 1 A/1 B-light chain 3(LC3) and PNI marker ubiquitin carboxy-terminal hydrolase(UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS In 109 cases of pancreatic cancer, 68.8%(75/109) had evidence of PNI and 61.5%(67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels(P < 0.05). LC3 expression was related to lymph node metastasis(P < 0.05) and was positively correlated with neural invasion(P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients(P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer(P < 0.05). CONCLUSION PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.

关键词： Pancreatic cancer Perineural invasion Autophagy Clinical pathological features Prognosis

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Phenotypic Classification of Well-Differentiated Gastric Adenocarcinoma

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Chinese Journal of Cancer Research 2009年第4期21卷 278-289页

作者： Ying Wu Zhong-wu Li Ji-you Li Key laboratory of Carcinogenesis and Translational Research （Ministry of Education） Department ofPathology Peking University School of Oncology Beijing Cancer Hospital ＆ Institute Beijing 100142China

Objective： To investigate the genotypes of well-differentiated non-cardiac gastric adenocarcinoma and their clinicopathological significance. Methods： Sixty-four cases of well-differentiated non-cardiac gastric adenocarcinoma were included in this study. The expressions of intestinal phenotypic markers including CDX2, MUC2, Li-cadherin, CD10, Hepatocyte（Hep） and Villin, and gastric phenotypic markers including MUC5AC and pS2 were detected immunohistochemically. Based on the expressions of phenotypic markers, 64 cases can be divided into four phenotypes. Cases only expressing intestinal phenotypic markers were classified as intestinal phenotype; cases only expressing gastric phenotypic markers as gastric phenotype; cases expressing both intestinal and gastric phenotypic markers as gastrointestinal phenotype; and cases expressing neither intestinal nor gastric phenotypic marker as null phenotype. The association of phenotype and clinic-pathological parameters was analyzed. We also detected the expressions of markers related to the development and progression of cancer, including Rb, P53, c-Met, MIF, TGF-β-RII, β-catenin, CD44v6 and E-cadherin. Results： Of 64 cases, 33（51.6%） were intestinal type, 3（4.7%） were gastric type, 25（39.1%） were gastrointestinal type and 3（4.7%） were null type. Fifty-eight cases were either intestinal or gastrointestinal type, which accounted for 90.6% of all the cases. In addition, there was an association between phenotype and biological behaviors （invasion or metastasis）. The biological behaviors of intestinal and gastrointestinal type were better than gastric type. Compared with intestinal, gastric and gastrointestinal types, the biological behaviors of null type were the most aggressive. The biological behaviors of gastric carcinoma tended to be better as the number of expression of intestinal markers increased. Expression of markers related to the development and progression of cancer was not significantly correlated with phenotypes a

关键词： Gastric carcinoma Phenotype Immunohistochemistry Biological behavior

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A 18FDG PET/CT-based volume parameter is a predictor of overall survival in patients with local advanced gastric cancer

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Chinese Journal of Cancer Research 2019年第4期31卷 632-640页

作者： Jinling Song Zhongwu Li Puyun Chen Jiangyuan Yu Feng Wang Zhi Yang Xuejuan Wang Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Nuclear MedicinePeking University Cancer Hospital&InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: The present study investigated the prognosis value of preoperative fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT) in patients with local advanced gastric cancer(LAGC).Methods: In total, 144 patients [median age 63(range: 48-80) years old] with LAGC underwent 18 F-FDG PET/CT prior to any treatment. The maximum standardized uptake values(SUVmax), mean standardized uptake values(SUVmean), metabolic tumor volume(MTV) and total lesion glycolysis(TLG) of the primary lesion were measured on PET/CT and correlated with clinicopathological features and ***: Significant differences in SUVmean, SUVmax, MTV and TLG were found according to Lauren’s classification, histologic grade and T category(P<0.05). During the 26.5-month follow-up, 51(35.4%) patients died and 70(48.6%) exhibited disease progression. The optimal thresholds of MTV and TLG were 15.1 cm^3 and 47.3 cm^3, respectively. The 3-year progression-free survival(PFS) and overall survival(OS) for patients with high TLG values were 30% and 38% compared to 38% and 47% for low TLG values, respectively(P<0.05). Univariate and multifactor analyses demonstrated that lymph node metastasis and T stage were independent prognostic factors for PFS;T stage, histologic grade and TLG were independent prognostic factors for OS(P<0.05). Molecular markers had no relationship with patient’s ***: Metabolic activity of primary gastric tumors from 18 F-FDG PET/CT is a prognostic factor in patients with LAGC.

关键词： Gastric cancer 18F-FDG PET/CT metabolic parameters prognosis

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MiR-301a transcriptionally activated by HIF-2αpromotes hypoxiainduced epithelial-mesenchymal transition by targeting TP63 in pancreatic cancer

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World Journal of Gastroenterology 2020年第19期26卷 2349-2373页

作者： Kun-Dong Zhang Bin Hu Gang Cen Yu-Han Yang Wei-Wei Chen Zeng-Ya Guo Xiao-Feng Wang Qian Zhao Zheng-Jun Qiu Department of General Surgery Shanghai Key Laboratory of Pancreatic DiseaseShanghai General HospitalShanghai Jiaotong UniversityShanghai 200080China Key laboratory of Cell Differentiation and Apoptosis of National Ministry of Education Department of Pathophysiology and Rui-Jin HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

BACKGROUND Pancreatic cancer(PC)is one of the deadliest cancers *** metastasis involves a complex set of events,including epithelial-mesenchymal transition(EMT),that increase tumor cell *** evidence has shown that hypoxia is a major EMT regulator in pancreatic cancer cells and facilitates metastasis;however,the mechanisms remain *** To investigate the role of miR-301a in hypoxia-induced EMT in PC *** Real-time PCR and Western blot analysis were used to detect the expression of miR-301a and EMT markers in PDAC cells cultured in hypoxic and normoxic *** blot analysis was used to detect the expression of EMT markers in PDAC cells with miR-301a *** healing assay and Transwell assay were used to detect the migration capabilities of PDAC cells with miR-301a overexpression and *** assay was used to detect the miR-301a promoter and the 3’untranslated region activity of *** PC mouse models were used to study the role of miR-301a in metastasis of PDAC cells in *** situ hybridization assay was used to detect the expression of miR-301a in PDAC patient samples(adjacent paratumor and paired tumor tissues).RESULTS Hypoxic environment could directly promote the EMT of PC *** expression level of miR-301a was increased in a HIF2αdependent manner in hypoxia-cultured CFPAC-1 and BxPC-3 *** of miR-301a enhanced the hypoxia-induced EMT of PC cells,while knocking out miR-301a result in the suppression of hypoxia-induced ***63 was a direct target of miR-301a and involved in the metastatic process of PC ***,miR-301a upregulation facilitated PDAC distant metastasis and lymph node metastasis in ***,miR-301a overexpression was indicative of aggressive clinicopathological behaviors and poor *** The newly identified HIF-2α-miR301a-TP63 signaling pathway may play a crucial role in hypoxia-induced EMT in PDAC cells.

关键词： MiR-301a Epithelial-mesenchymal transition Pancreatic cancer Hypoxia HIF-2α TP63

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Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGFβ2/NF-κB/Kindlin-2 axis

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Chinese Journal of Cancer Research 2020年第1期32卷 72-88页

作者： Zhu Wang Yang Yang Yancheng Cui Chao Wang Zhiyong Lai Yansen Li Wei Zhang Harri Mustonen Pauli Puolakkainen Yingjiang Ye Kewei Jiang Zhanlong Shen Shan Wang Department of Gastroenterological Surgery Peking University People’s HospitalBeijing 100044China laboratory of Surgical Oncology Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment ResearchPeking University People’s HospitalBeijing 100044China Department of Surgery Helsinki University Central Hospitaland University of HelsinkiHelsinki 00290Finland

Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer(GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be ***: THP-1 monocytes were induced by PMA/interleukin(IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation(Ch IP) assay were used to investigate the mechanism of transforming growth factor β2(TGFβ2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in ***: We found that Kindlin-2 expression was upregulated at both m RNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFβ2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFβ2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in ***: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFβ2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.

关键词： Gastric cancer tumor-associated macrophage Kindlin-2 invasion and metastasis

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Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma:comparison of long-term outcome between radiotherapy and chemotherapy

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International Journal of Ophthalmology(English edition) 2023年第3期16卷 402-410页

作者： Xiao-Feng Li Rui-Qi Ma Xue Wu Lu Gan Zhi-Yu Peng Jiang Qian Department of Ophthalmology Eye and ENT Hospital of Fudan UniversityShanghai 200031China laboratory of Myopia Chinese Academy of Medical SciencesShanghai 200031China NHC Key laboratory of Myopia Fudan UniversityShanghai 200031China Department of Ophthalmology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

AIM:To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma(NRSTS),and to compare the treatment outcome between postoperative radiotherapy(RT) and chemotherapy in a retrospective analysis nearly ***:A retrospective cohort study of 56 patients with orbital NRSTS were reviewed,34 of whom received postoperative RT,and 22 received postoperative *** clinicopathological features,local recurrence,metastases,and survival data were *** analysis was performed using the Kaplan-Meier ***:During follow-up(111.8mo,ranged 8-233mo) for 56 patients,19 patients of them developed local recurrence,and 7 patients developed distant *** patients died during follow-up *** survival rates considering the whole study group was 78.57% at 5y,and 72.16% at 10y after the initial *** with chemotherapy,RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy,0.263,95% confidence interval(CI),0.095-0.728,P=0.0015];with lower risk of distant metastasis(hazard ratio for RT vs chemotherapy,0.073,95%CI,0.015-0.364,P=0.0014);and with lower risk of death from disease(hazard ratio for RT vs chemotherapy,0.066,95%CI,0.022-0.200,P<0.0001).The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy ***:In patients with orbital NRSTS,postoperative RT provides better control of local recurrence,distant metastasis,and death from disease than *** is the more preferrable adjuvant therapy compared to chemotherapy possibly.

关键词： orbital tumor non-rhabdomyosarcoma soft tissue sarcoma oncological outcome adjuvant radiotherapy adjuvant chemotherapy

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Oncoprotein HBXIP promotes tumorigenesis through MAPK/ERK pathway activation in non-small cell lung cancer

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Cancer Biology & Medicine 2021年第1期18卷 105-119页

作者： Jun Zhang Bei Sun Xianhui Ruan Xiukun Hou Jingtai Zhi Xiangrui Meng Xiangqian Zheng Ming Gao Department of Breast Cancer Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Outpatient Office Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Thyroid and Neck Tumor Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Lymphoma Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Objective:The oncoprotein,hepatitis B X-interacting protein(HBXIP),has been reported to play an important role in human ***,its functions in non-small cell lung cancer(NSCLC)are poorly *** goal of the present study was to identify the role of HBXIP in the regulation of NSCLC ***:The level of HBXIP expression in NSCLC tissue was assessed by immunohistochemical and Western blot analyses,and its relationships with clinicopathological features and outcomes were statistically *** effects of HBXIP on NSCLC cell progression were assessed through cell viability,colony formation,and flow cytometry analyses in *** mechanism by which HBXIP regulated the MAPK pathway was studied by Western blot,immunofluorescence,and immunoprecipitation *** addition,in vivo experiments were performed to evaluate the progression of NSCLC and ERK signaling pathway activation after HBXIP ***:HBXIP was overexpressed in human NSCLC and was correlated with the invasiveness of *** high expression of HBXIP in NSCLC was significantly correlated with gender(P=0.033),N stage(P=0.002),and tumor-node-metastasis stage(P=0.008).In vitro experiments using an NSCLC cell line revealed that HBXIP knockdown resulted in the suppression of cell proliferation and colony formation,which was consistent with the enhanced cell cycle arrest in G1 *** results of a mechanistic investigation suggested that binding of HBXIP to MEK1 protein promoted MAPK/ERK signaling pathway activation in NSCLC by preventing the proteasome-mediated degradation of *** addition,the results obtained using in vivo subcutaneous tumor xenografts confirmed that HBXIP deficiency decreased MEK1 protein levels and NSCLC tumor ***:Taken together,our results showed that the HBXIP-MEK interaction promoted oncogenesis via the MAPK/ERK pathway,which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant featur

关键词： HBXIP non-small cell lung cancer MEK1 tumor progression

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