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Copy number alteration profiling facilitates differential diagnosis between ossifying fibroma and fibrous dysplasia of the jaws

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International Journal of Oral Science 2021年第2期13卷 200-209页

作者： Ming Ma Lu Liu Ruirui Shi Jianyun Zhang Xiaotian Li Xuefen Li Jiaying Bai Jianbin Wang Yanyi Huang Tiejun Li Department of Oral Pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina Beijing Advanced Innovation Center for Genomics(ICG) Biomedical Pioneering Innovation Center(BIOPIC)School of Life SciencesPeking UniversityBeijingChina Central laboratory Peking University School and Hospital of StomatologyBeijingChina School of Life Sciences and Beijing Advanced Innovation Center for Structural Biology Tsinghua UniversityBeijingChina College of Chemistry and Molecular Engineering and Beijing National laboratory for Molecular Sciences Peking UniversityBeijingChina Institute for Cell Analysis Shenzhen Bay LaboratoryGuangdongChina

Ossifying fibroma(OF)and fibrous dysplasia(FD)are two fibro-osseous lesions with overlapping clinicopathological features,making diagnosis *** this study,we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations(CNAs)using minute amounts of DNA extracted from morphologically correlated microdissected tissue *** frozen tissue specimens from OF(n=29)and FD(n=28)patients were obtained for *** fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection(LCM),with~30–50 cells(5000–10000µm2)per *** found that the rate of recurrent CNAs in OF cases was much higher(44.8%,13 of 29)than that in FD cases(3.6%,1 of 28).Sixty-nine percent(9 of 13)of the CNA-containing OF cases involved segmental amplifications and deletions on Chrs 7 and *** also identified eight CNA-associated genes(HILPDA,CALD1,C1GALT1,MICALL2,PHF14,AIMP2,MDM2,and CDK4)with amplified expression,which was consistent with the copy number *** further confirmed a jaw lesion with a previous uncertain diagnosis due to its ambiguous morphological features and the absence of GNAS mutation as OF based on the typical Chr 12 amplification pattern in its CNA ***,analysis of a set of longitudinal samples collected from an individual with a cellular lesion in suspicion of OF at the first surgery,recurrence and the latest malignant transformation revealed identical CNA patterns at the three time points,suggesting that copy number profiling can be used as an important tool to identify borderline lesions or lesions with malignant ***,CNA profiling of fibro-osseous lesions can greatly improve differential diagnosis between OF and FD and help predict disease progression.

关键词： diagnosis precise profiling

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Myofibrillogenesis regulator-1 overexpression is associated with poor prognosis of gastric cancer patients

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World Journal of Gastroenterology 2012年第38期18卷 5434-5441页

作者： ling Guo Bin Dong Jia-Fu Ji Ai-Wen Wu Key laboratory of Carcino-genesis and Translational Research(Mlmstry of Education) Department of Gastrointestinal SurgeryPeking UniversityCancer HospitalBeijing Cancer Hospital and InstituteBeijing100142China Key laboratory of Carcinogenesis and TranslationalResearch(Ministry of Education) Department of PathologyPeking University Cancer HospitalBeijing Cancer Hospitaland InstituteBeijing 100142China

AIM: To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer. METHODS: In our previous study of human wholegenome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records. RESULTS: MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stageⅠ-Ⅳ carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27

关键词： Myofibrillogenesis regulator-1 Gastric cancer Real-time quantitative reverse transcriptase-polymerase chain reaction Immunohistochemistry Poor prognosis

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CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

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Journal of Genetics and Genomics 2024年第2期51卷 184-196页

作者： Yan Shi Chunyan Cao Yiheng Zeng Yuanliang Ding Long Chen Fuze Zheng Xuejiao Chen Fanggui Zhou Xiefeng Yang Jinjing Li Liuqing Xu Guorong Xu Minting Lin Hiroyuki Ishiura Shoji Tsuji Ning Wang Zhiqiang Wang Wan-Jin Chen Kang Yang Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China Department of Neurology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China The First Affiliated Hospital College of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan 471000China Department of Neurology Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujian 363000China Department of Neurology Jian'ou Municipal Hospital of Fujian ProvinceJian'ouFujian 353100China Department of Radiology First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China Department of Neurology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Neurology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan Institute of Medical Genomics International University of Health and WelfareChiba 286-0048Japan

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with ***,since only three patients from a single family were reported,it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/***,using repeat-primed-polymerase chain reaction and long-read sequencing,we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1,typically presenting with oculopharyngodistal *** CGG repeat expansions range from 161 to 669 repeat *** of the patients present with ptosis,restricted eye movements,dysphagia,dysarthria,and diffuse limb muscle *** one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance *** biopsies from three patients show a myopathic pattern and rimmed *** of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity,suggesting that RNA toxicity and mitochondrial dysfunction may contribute to *** study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

关键词： Oculopharyngeal myopathy with leukoencephalopathy Oculopharyngodistal myopathy CGG repeat expansion Rimmed vacuoles

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Expressions of cyclin E, cyclin dependent kinase 2 and p57^(KIP2) in human gastric cancer

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Chinese Medical Journal 2003年第1期116卷 20-23页

作者：梁斌王杉杨晓东叶颖江于永祥崔志荣 Department of Surgery and laboratory of Surgical Oncology

Objective To investigate the expressions of cyclin E, cyclin dependent kinase 2(CDK-2)and cyclin-dependent kinase inhibitor p57 KIP2 in human gastric cancer, and to evaluate the relationships between protein levels and clinicopathological parameters. Methods Western blot was used to measure the expressions of cyclin E, CDK-2 and p57 KIP2 proteins in the surgically resected gastric carcinoma, adjacent normal mucosa and metastatic lymph nodes from 36 patients. Results Cyclin E and CDK-2 protein levels were higher in gastric cancer tissues in comparison with normal tissues (P0.05). Expression of cyclin E and CDK-2 showed a positive linear correlation (r=0.451, P=0.01). Protein levels of p57 KIP2 were lower in gastric cancer tissues than in the normal mucosa (P0.05). In metastatic lymph nodes, expression of cyclin E was increased and the expression of p57 KIP2 decreased. Conclusion Overexpressions of cyclin E, CDK-2 and downregulated expression of p57 KIP2 may play important roles in tumorigenesis and metastatic potential of gastric cancer.

关键词： stomach neoplasms cyclin E cyclin dependent kinase 2 cyclin-dependent kinase inhibitor

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Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

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Chinese Journal of Cancer Research 2022年第4期34卷 383-394页

作者： Changlong Li Zhen Guan Yi Zhao Tingting Sun Zhongwu Li Weihu Wang Zhexuan Li Lin Wang Aiwen Wu Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of RadiologyPeking University Cancer Hospital&InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Radiation OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Cancer EpidemiologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:The accurate prediction of tumor response to neoadjuvant chemoradiotherapy(nCRT)remains *** studies have investigated pathologic complete response(ypCR)prediction in patients with residual flat mucosal lesions after *** study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer(LARC).Methods:Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer *** and multivariate analyses of the association between clinicopathological factors and ypCR were performed,and a nomogram was constructed by incorporating the significant ***:Of the 246 patients with residual flat mucosal lesions included in the final analysis,56(22.8%)had *** and multivariate analyses showed that pretreatment cT stage(pre-cT)≤T2(P=0.016),magnetic resonance tumor regression grade(MR-TRG)1-3(P=0.001)and residual mucosal lesion depth=0 mm(P<0.001)were associated with a higher rate of ypCR.A nomogram was developed with a concordance index(C-index)of0.759 and the calibration curve showed that the nomogram model had good predictive *** follow-up time ranged from 3.0 to 113.3 months,with a median follow-up time of 63.77 *** multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival(DFS)or overall survival(OS).Conclusions:Completely flat mucosa,early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after *** mucosal re-evaluation before surgery is important,as it may contribute to decision-making and facilitate nonoperative management or organ preservation.

关键词： Rectal cancer preoperative chemoradiotherapy tumor regression grade flat mucosal lesions pathologic complete response

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Preoperative contrast-enhanced computed tomography-based radiomics model for overall survival prediction in hepatocellular carcinoma

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World Journal of Gastroenterology 2022年第31期28卷 4376-4389页

作者： Peng-Zhan Deng Bi-Geng Zhao Xian-Hui Huang Ting-Feng Xu Zi-Jun Chen Qiu-Feng Wei Xiao-Yi Liu Yu-Qi Guo Sheng-Guang Yuan Wei-Jia Liao laboratory of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Guilin Medical UniversityGuilin 541001Guangxi Zhuang Autonomous RegionChina

BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver malignancy with a rising incidence *** prognosis of HCC patients after radical resection remains *** is a novel machine learning method that extracts quantitative features from medical images and provides predictive information of cancer,which can assist with cancer diagnosis,therapeutic decision-making and prognosis *** To develop and validate a contrast-enhanced computed tomography-based radiomics model for predicting the overall survival(OS)of HCC patients after radical *** A total of 150 HCC patients were randomly divided into a training cohort(n=107)and a validation cohort(n=43).Radiomics features were extracted from the entire tumour *** least absolute shrinkage and selection operator algorithm was applied for the selection of radiomics features and the construction of the radiomics *** and multivariate Cox regression analyses were used to identify the independent prognostic factors and develop the predictive nomogram,incorporating clinicopathological characteristics and the radiomics *** accuracy of the nomogram was assessed with the concordance index,receiver operating characteristic(ROC)curve and calibration *** clinical utility was evaluated by decision curve analysis(DCA).Kaplan–Meier methodology was used to compare the survival between the low-and high-risk *** In total,seven radiomics features were selected to construct the radiomics *** to the results of univariate and multivariate Cox regression analyses,alpha-fetoprotein(AFP),neutrophil-to-lymphocyte ratio(NLR)and radiomics signature were included to build the *** C-indices of the nomogram in the training and validation cohorts were 0.736 and 0.774,*** curve analysis for predicting 1-,3-,and 5-year OS confirmed satisfactory accuracy[training cohort,area under the curve(AUC)=0.850,0.791 and

关键词： Hepatocellular carcinoma Radiomics Contrast-enhanced computed tomography Survival prediction

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Children with lysinuric protein intolerance: Experience from a lower middle income country

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World Journal of Clinical Pediatrics 2022年第4期11卷 369-374页

作者： Syed Bilal Hashmi Sibtain Ahmed Department of Pathology and laboratory Medicine Aga Khan University HospitalKarachi 74800Pakistan

BACKGROUND Lysinuric protein intolerance(LPI)is an inborn error of metabolism consequential to recessive mutations in the SLC7A7 *** metabolic imbalance in absorption and excretion of dibasic amino acids is considered the basis of *** disease results from protein intolerance with signs and symptoms oscillating from cerebral impairment,respiratory involvement,renal failure and autoimmune *** To determine biochemical and clinical presentation of cases with biochemical picture suggestive of LPI in Pakistani *** The study was conducted at the Biochemical Genetic Lab,Department of Pathology and laboratory Medicine,AKU Plasma,and urine amino acid quantification data from January 2013 to October 2018 was included in this *** amino acids were analyzed by high performance liquid *** requisition forms were used to obtain the clinicopathological *** analysis was done by Microsoft Excel *** A total of 6 patients were *** the patients were male(100%).The mean age was 24 mo±10 *** the patients had low plasma concentration of lysine,ornithine and arginine,whereas increased levels of lysine,ornithine and arginine in urine were observed in 2 *** of consanguineous marriage was present in all patients(100%).The most observed clinical symptom was feeding difficulty followed by failure to thrive(83.3%)and developmental delay(66.6%).Hepatomegaly was present in all patients(100%).No mutation analysis was *** This study portrays the biochemical and clinical spectrum of LPI in *** clinical manifestations appeared in the first 2 years of life,most of them suffered a delay in undergoing diagnostic workup.

关键词： Lysinuric protein intolerance Consanguinity Pakistan Retrospective study

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STIM1 overexpression in hypoxia microenvironment contributes to pancreatic carcinoma progression

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Cancer Biology & Medicine 2019年第1期16卷 100-108页

作者： Jian Wang Junling Shen Kaili Zhao Jinmeng Hu Jiuxing Dong Jianwei Sun Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer State Key laboratory for Conservation and Utilization of Bio-Resources in Yunnan Center for Life SciencesSchool of Life Sciences Yunnan University

Objective: Stromal interaction molecule 1(STIM1) overexpression has been reported to play an important role in progression of several cancers. However, the mechanism of STIM1 overexpression and its relationship with hypoxia in pancreatic ductal adenocarcinoma(PDAC) remains ***: STIM1 and HIF-1α expression was tested using immunohistochemistry in tissue microarray(TMA) including pancreatic cancer and matched normal pancreatic tissues, and their relationships with clinicopathological parameters were statistically analyzed. q-PCR, Western blot, Ch IP, and luciferase assay were employed to 030 analyze transcriptional regulation between HIF-1α and STIM1 in pancreatic cancer PANC-1 ***: Both STIM1 and HIF-1α showed higher positive rates and up-regulated expression in cancer tissues compared to that of normal tissues(P < 0.05). The Kaplan–Meier method revealed that higher HIF-1α and STIM1 expression levels were significantly correlated with decreased disease-free survival(P = 0.025 and P = 0.029, respectively). The expression of HIF-1α showed a significant positive correlation with that of STIM1 in cancer tissues(rs = 0.3343, P = 0.0011) and pancreatic cancer cell ***, Ch IP and luciferase assays confirmed that HIF-1α bound to the STIM1 promoter and regulated its expression in PANC-1 ***: In hypoxia microenvironment, up-regulated expression of STIM1 mediated by HIF-1α promotes PDAC progression. HIF-1α and STIM1 are potential prognostic markers and/or therapeutic targets for PDAC treatment.

关键词： Pancreatic cancer STIM1 HIF-1α

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PYK2 mediates the BRAF inhibitor (vermurafenib)-induced invadopodia formation and metastasis in melanomas

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Cancer Biology & Medicine 2022年第8期19卷 1211-1223页

作者： Junling Shen Jilong Yang Lei Sang Rui Sun Weiyu Bai Chao Wang Yan Sun Jianwei Sun Center for Life Sciences School of Life SciencesState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanYunnan UniversityKunming 650091China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjinChina

Objective:The BRAF inhibitor,vemurafenib,has been widely used in the treatment of patients with melanoma-bearing BRAFV600E *** the initial response to vemurafenib is usually excellent,the majority of patients eventually develop resistance and metastatic ***,the underlying molecular mechanism remains *** objective of this study was therefore to identify additional molecular targets responsible for vemurafenib ***:Western blots and immunohistochemistry analyses were used to evaluate expressions of PYK2 and p-PYK2 in cultured cells and melanoma tissue *** relationships of p-PYK2 with clinicopathological parameters were statistically *** cell invasion,and a Ca2+assay were used to determine the effect of vemurafenib resistance-induced p-PYK2 on melanoma progression.A mouse model was used to assess the effects of PYK2 on melanoma ***:Elevated p-PYK2 levels were detected in vemurafenib-resistant melanoma cells,and PYK2 was shown to regulate invadopodia formation in melanoma *** triggered invadopodia formation by activation of *** of PYK2 with either shRNA or the small molecule inhibitor,PF562711,dramatically reduced vemurafenib-induced invadopodia ***,knockdown of PYK2 significantly reduced melanoma lung metastasis in *** expressions of p-PYK2 in melanoma patients were positively correlated with advanced stage(P=0.002),metastasis(P<0.001),and Clark grade(P<0.001),and were also associated with short overall survival[hazard ratio(HR)=3.304,P=0.007]and progression-free survival(HR=2.930,P=0.001).Conclusions:PYK2 mediated vemurafenib-induced melanoma cell migration and *** of PYK2 resensitized melanoma cells to ***-PYK2 was a prognostic biomarker in melanoma patients.

关键词： STIM1 Pyk2 invadopodia invasion melanoma vemurafenib

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Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis

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World Journal of Gastroenterology 2012年第4期18卷 368-374页

作者： Meng-Meng Tian,Yu Sun,Zhong-Wu Li,Ying Wu,Ai-Lian Zhao,Ji-You Li,Key laboratory of Carcinogenesis and Translational Research,Department of Pathology,Peking University School of Oncology,Beijing Cancer Hospital and Institute,Beijing 100142,China Key laboratory of Carcinogenesis and Translational Research Department of Pathology Peking University School of Oncology Beijing Cancer Hospital and Institute Beijing 100142 China.

AIM:To investigate the association between single nu-cleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk,biological behavior and prognosis of gastric cancer (GC) in Chinese ***:The study group consisted of 332 GC patients and 380 healthy *** was performed using polymerase chain reaction and the results were confirmed by *** associa-tion of ICAM-1 K469E polymorphisms and the risk of GC were studied,and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was ***:Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios:1.36;95% confidence in-terval (CI):1.01-1.84;P=0.041].GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%,respectively;P=0.002).In addition,patients at stage Ⅳ had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%,re-spectively;P=0.046).Follow-up study showed that the overall cumulative survival rate was 23.7% in AA geno-type group and 42.9% in AG and GG genotypes *** univariate analysis,AA genotype was correlated with the overall cumulative survival (P=0.034).But in multi-variate analysis,ICAM-1 polymorphism was not an inde-pendent prognostic factor for the overall survival (relative risk,1.145;95% CI:0.851-1.540;P=0.370).CONCLUSION:Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC,predicting disease progression,and guiding individualized treatment.

关键词： Intercellular adhesion molecule-i Genepoiymorphism Gastric cancer Risk Prognosis

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