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Bioinformatics Analysis and Identification of Potential Genes Associated with Pathogenesis and Prognosis of Gastric cancer

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Current medical Science 2022年第2期42卷 357-372页

作者： Dan-wen WANG Fei SU Li-jie YANG Li-wen SHI Tie-cheng YANG Hua-qiao WANG Xuan-fei LI Mao-hui FENG Department of Gastrointestinal Surgery Zhongnan Hospital of Wuhan UniversityWuhan443071China clinical medical research center of peritoneal cancer of wuhan Wuhan443071China clinical cancer Study center of Hubei Provence Wuhan443071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan443071China Department of Oncology the First Hospital of Lanzhou UniversityLanzhou730000China

Objective Gastric cancer(GC)is a deadly cancer and a challenging public health problem *** study aimed to analyze potential genes associated with pathogenesis and prognosis of gastric *** This work selected the overlapping differentially expressed genes(DEGs)in GC from four datasets,the GSE29272,GSE29998,GSE54129 and GSE118916 Gene Expression Omnibus *** DEGs were used to carry out comprehensive bioinformatic analysis to analyze the related functions and pathways enriched,the relative expression levels and immune infiltrates,the prognostic characteristics and the interaction *** In total,55 DEGs increased while 98 decreased in their expression *** those DEGs with increased expression,they were mostly concentrated on“focal adhesion”and“ECM-receptor interaction”,whereas DEGs with decreased expression were mostly associated with“gastric acid secretion”and“drug metabolism cytochrome P450”.MCODE and ClueGO results were then integrated to screen 10 hub genes,which were FN1,COL1A1,COL3A1,BGN,TIMP1,COL1A2,LUM,VCAN,COL5A2 and *** analysis revealed that higher expression of the ten hub genes significantly predicted lower overall survival of GC ***1 was most significantly related to neutrophils,CD8+T cells,as well as dendritic cells,while LUM was most significantly related to *** Immunohistochemistry results and functional testing showed that the expression of COL5A2 was elevated in GC and that it might be a key gene in GC tumorigenesis.

关键词： gastric cancer differentially expressed genes bioinformatics analysis prognosis immune infiltrate

Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis

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World Journal of Gastroenterology 2008年第8期14卷 1159-1166页

作者： Hassan Alaa Hammed al-Shammaa Yan Li Yutaka Yonemura Department of Oncology Zhongnan Hospital of Wuhan University CancerCenter of Wuhan University and Hubei Cancer Clinical StudyCenter No 169 Donghu Road Wuchang District Wuhan 430071Hubei Province China peritoneal Carcinomatosis Program Shizuoka Cancer Center Mishima Japan

This article is to offer a concise review on the use of cytoreductive surgery （CRS） plus intraperitoneal hyperthermic chemotherapy （IPHC） for the treatment of peritoneal carcinomatosis （PC）. Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 too. With the establishment of several phase Ⅱ studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase Ⅲ studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future.

关键词： peritoneal carcinomatosis Cytoreductive surgery Intraperitoneal hyperthermic chemotherapy Gastric cancer Colorectal cancer Ovarian cancer peritoneal mesothelioma

Laparoscopy-assisted gastrectomy for advanced gastric cancer patients with situs inversus totalis: Two case reports and review of literature

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World Journal of Gastrointestinal Surgery 2023年第9期15卷 2063-2073页

作者： Hong-Bo Liu Xiao-Peng Cai Zhao Lu Bin Xiong Chun-Wei Peng Department of Gastrointestinal Surgery Hubei Key Laboratory of Tumor Biological Behaviors&Hubei Cancer Clinical Study CenterWuhan Peritoneal Cancer Clinical Medical CenterZhongnan Hospital of Wuhan UniversityWuhan 430070Hubei ProvinceChina School of Nursing Wuhan UniversityWuhan 430070Hubei ProvinceChina

BACKGROUND Situs inversus totalis(SIT)is a rare condition in which the positions of abdominal and thoracic organs present a“mirror image”of the normal ones in the median sagittal *** minimally invasive surgery has evolved to achieve laparoscopic gastrectomy for gastric cancer(GC)patients with SIT,it is difficult to perform lymphadenectomy(LND)in such a transposed anatomical ***,we report the cases of two patients with SIT who successfully underwent laparoscopy-assisted gastrectomy(LAG)with D2 *** SUMMARY Case 1:A 65-year-old man was admitted for intermittent abdominal pain and distension,occasional belching,and acid reflux for 4 *** was diagnosed with GC(cT3N1-2M0)with *** surgery,he had undergone four cycles of neoadjuvant chemotherapy and ***,the patient was evaluated as having a partial response,and laparoscopy-assisted distal gastrectomy with D2 LND and Billroth II reconstruction were *** operation was performed successfully within 240 min with an estimated blood loss of 50 mL and no severe *** patient was discharged on postoperative day(POD)*** 2:A 55-year-old man was admitted for upper abdominal distension with pain and discomfort after eating for 3 *** was diagnosed with GC(cT3N1M0)with *** had a history of hypertension for more than 10 years;however,his blood pressure was well-controlled via regular *** performed laparoscopy-assisted total gastrectomy with D2 LND and Roux-en-Y *** operation was performed successfully within 168 min with an estimated blood loss of 50 mL and no severe *** patient was discharged on POD *** LAG with D2 LND could be considered an accessible,safe,and curative procedure for advanced GC patients with SIT.

关键词： Situs inversus totalis Laparoscopy-assisted gastrectomy Advanced gastric cancer Surgery modality Lymphadenectomy Case report

Neuroanatomical Circuitry between Kidney and Rostral Elements of Brain： a Virally Mediated Transsynaptic Tracing Study in Mice

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Journal of Huazhong University of Science and Technology(medical Sciences) 2017年第1期37卷 63-69页

作者：周业庭何志刚刘涛涛冯茂辉张定宇项红兵 Department of Surgery Shuyang Hospital Shuyang 223600 China Department of Anesthesiology and Pain Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Oncology Wuhan Peritoneal Cancer Clinical Medical Research Center Zhangnan Hospital of Wuhan University Wuhan 430071 China Intensive Care Unit Wuhan Medical Treatment Center Wuhan 430023 China

The identity of higher-order neurons and circuits playing an associative role to control renal function is not well understood. We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3–6 days after injecting a retrograde tracer pseudorabies virus（PRV）-614 into kidney of 13 adult male C57BL/6J strain mice. PRV-614 infected neurons were detected in a number of mesencephalic（e.g. central amygdala nucleus）, telencephalic regions and motor cortex. These divisions included the preoptic area（POA）, dorsomedial hypothalamus（DMH）, lateral hypothalamus, arcuate nucleus（Arc）, suprachiasmatic nucleus（SCN）, periventricular hypothalamus（Pe H）, and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus（PVN）. PRV-614/Tyrosine hydroxylase（TH） double-labeled cells were found within DMH, Arc, SCN, Pe H, PVN, the anterodorsal and medial POA. A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic. PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin. These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.

关键词： kidney hypothalamus autonomic control alpha-herpes virus tryptophan hydroxylase tyrosine hydroxylase arginine vasopressin oxytocin

Prediction of Tumor Microenvironment Characteristics and Treatment Response in Lung Squamous Cell Carcinoma by Pseudogene OR7E47P-related Immune Genes

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Current medical Science 2023年第6期43卷 1133-1150页

作者： Ya-qi ZHAO Hao-han ZHANG Jie WU Lan LI Jing LI Hao ZHONG Yan JIN Tian-yu LEI Xin-yi ZHAO Bin XU Qi-bin SONG Jie HE cancer center Renmin Hospital of Wuhan UniversityWuhan430060China Department of medical Oncology First Affiliated Hospital of Kunming Medical UniversityKunming650000China National cancer center/National clinical research center for cancer/cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100032China

Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional *** receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods clinical and molecular information from The cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for *** Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation *** OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal *** to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related *** clustering performed well in the internal and 5 external validation *** on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment *** addition,the ORPScore was a bette

关键词： pseudogene olfactory receptor family 7 subfamily E member 47 pseudogene-related immune gene tumor microenvironment immunotherapy lung squamous cell carcinoma

Survival outcomes and prognostic indicators for gastric cancer patients with positive peritoneal wash cytology but no peritoneal metastasis after radical gastrectomy

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World Journal of Gastrointestinal Oncology 2021年第1期13卷 24-36页

作者： Wen-Zhe Kang Yu-Xin Zhong Fu-Hai Ma Li-Yan Xue Jian-Ping Xiong Shuai Ma Yang Li Yi-Bin Xie Xu Quan Yan-Tao Tian Department of Pancreatic and Gastric Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100021China

BACKGROUND Positive peritoneal wash cytology with no peritoneal metastasis(CY1P0)is a special type of distant gastric cancer metastasis,which describes a patient with positive peritoneal lavage cytology,but no definitive peritoneal metastasis,and there are no widely accepted treatment *** enrolled 48 primary CY1P0 gastric cancer patients treated by radical gastrectomy in this *** study illustrated the efficacy of radical gastrectomy for CY1P0 gastric cancer patients,and suggested that the pathological N factor and vascular invasion were significant independent risk factors for overall survival(OS).AIM To assess the survival of CY1P0 gastric cancer patient post-radical gastrectomy,and to identify factors associated with long-term *** Our study included 48 patients with primary CY1P0 gastric cancer who had radical gastrectomies at the cancer Hospital,Chinese Academy of medical Sciences,Beijing,China between 2013 and 2018.R0 resection was achieved in all 48 *** patients received neoadjuvant *** patients received adjuvant chemotherapy and four received adjuvant *** statistics were available for 48 ***-up continued through March *** and multivariate analyses were performed using a Cox proportional hazards model to identify prognostic *** Median OS was 22.0 mo(95%confidence interval:13.366-30.634 mo)*** analyses demonstrated that tumor site(P=0.021),pathological N factor(P=0.001),pathological T factor(P=0.028),vascular invasion(P=0.046),and the level of CA199 prior to initiating therapy(P=0.002)were significant risk factors for *** analyses demonstrated that pathological N factor(P=0.001)and vascular invasion(P=0.031)were significant independent risk factors for *** This study suggested that radical gastrectomy may be efficient for CY1P0 gastric cancer patient post-radical gastrectomy and the pathological N factor and vas

关键词： Gastric cancer Overall survival R0 resection Prognostic factors Lymph node metastasis

Minimizing the ratio of ionizable lipid in lipid nanoparticles for in vivo base editing

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National Science Review 2024年第6期11卷 285-293页

作者： Qiubing Chen Xuebin Wang Yizhou Zhang Ming Tian Junyi Duan Ying Zhang Hao Yin Departments of Urology and Laboratory Medicine Frontier Science Center for Immunology and Metabolism Medical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan University State Key Laboratory of Virology Tai Kang Center for Life and Medical Sciences Tai Kang Medical SchoolWuhan University Department of Rheumatology and Immunology Zhongnan Hospital of Wuhan UniversityWuhan University wuhan research center for Infectious Diseases and cancer Chinese Academy of Medical Sciences RNA Institute Wuhan University

Lipid nanoparticles(LNPs) have gained clinical approval as carriers for both siRNA and mRNA. Among the crucial components of LNPs, ionizable lipids play a pivotal role in determining the efficiency of RNA delivery. In this study, we synthesized a series of ionizable lipids, denoted as HTO, with a higher count of hydroxyl groups compared to SM-102. Remarkably, LNPs based on HTO12 lipid demonstrated comparable mRNA delivery efficiency and biosafety to those based on SM-102. However, the former reduced the ratio of ionizable lipid/total lipids to mRNA in LNPs by 2.5 times compared to SM-102. The HTO12 LNP efficiently encapsulated adenine base editor mRNA and sgRNA targeting Pcsk9, leading to substantial gene editing within the liver of mice and effective reduction of the target protein. Our study underscores that ionizable lipids with multiple hydroxyl groups may facilitate an improved lipid-to-mRNA ratio to minimize the dosage of ionizable lipids for in vivo delivery.

关键词： ionizable lipid lipid nanoparticle mRNA delivery base editor delivery Pcsk9

Identification and Validation of SLC9A2 as A Potential Tumor Suppressor in Colorectal cancer:Integrating Bioinformatics Analysis with Experimental Confirmation

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Current medical Science 2024年第3期44卷 529-544页

作者： Yan-min LIU Tie-cheng YANG Xiao-chang FANG Li-jie YANG Li-wen SHI Hua-qiao WANG Ting-ting DOU Lin SHU Tian-Liang CHEN Jun HU Xiao-ming YU Xuan-fei LI Department of Gastroenterology the Central Hospital of WuhanKey Laboratory for Molecular Diagnosis of Hubei ProvinceTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430014China Department of Gastrointestinal Surgery Zhongnan Hospital of Wuhan UniversityWuhan430071China clinical medical research center of peritoneal cancer of wuhan Wuhan430071China Hubei Provincial clinical research center for cancer Hubei Key Laboratory of Tumor Biological Behavi Wuhan430071China Department of General Surgery Taihe HospitalHubei University of MedicineShiyan442000China Department of Gastrointestinal Surgery Huangshi Central HospitalAffiliated Hospital of Hubei Polytechnic UniversityWuhan435001China

Objective To uncover the mechanisms underlying the development of colorectal cancer(CRC),we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and *** We performed Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis on differentially expressed genes(DEGs),constructed a protein-protein interaction(PPI)network to find the top 10 hub genes,and analyzed their expression in colon adenocarcinoma(COAD)and rectum adenocarcinoma(READ).We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western *** experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and *** We found 130 DEGs,with 45 up-regulated and 85 down-regulated in *** analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH,zymogen granules,and transmembrane transporter *** pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion,rheumatoid arthritis,and the IL-17 signaling *** identified 10 hub genes:CXCL1,SLC26A3,CXCL2,MMP7,MMP1,SLC9A2,SLC4A4,CLCA1,CLCA4,and *** enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of *** expression analysis revealed that CXCL1,CXCL2,MMP1,and MMP7 were highly expressed in CRC,whereas CLCA1,CLCA4,SLC4A4,SLC9A2,SLC26A3,and ZG16 were expressed at lower *** analysis revealed that 5 key genes were significantly associated with the prognosis of *** mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell ***,SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation,migration,and *** blotting analysis revealed tha

关键词： SLC9A2 colorectal cancer bioinformatic analysis biomarkers immune infiltrate

Efficacy and toxicity of capecitabine combined with intensitymodulated radiotherapy after D1/D2 lymph node dissection in patients with gastric cancer

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1532-1543页

作者： Xin Wang Wei-Hu Wang Shu-Lian Wang Yong-Wen Song Yue-Ping Liu Yuan Tang Ning Li Wen-Yang Liu Hui Fang Ye-Xiong Li Dong-Bing Zhao Yihebali Chi Lin Yang Jing Jin Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Radiation Oncology Peking University Cancer Hospital and InstituteBeijing 100001China Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116Guangdong ProvinceChina Department of Pancreatic and Gastric Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND Adjuvant chemoradiotherapy(ACRT)with oral capecitabine and intensitymodulated radiotherapy(IMRT)were well tolerated in a phase I study in patients who had undergone partial or total gastrectomy for locally advanced gastric cancer(GC).This phase II study aimed to further determine the efficacy and toxicity of this combination after radical resection and D1/D2 lymph node dissection(LND)for patients with locally advanced *** To further determine the efficacy and toxicity of this combination after radical resection and D1/D2 LND for patients with locally advanced *** Forty patients(median age,53 years;range,24-71 years)with pathologically confirmed adenocarcinoma who underwent D1/D2 LND were included in this *** patients received ACRT comprising IMRT(total irradiation dose:45 Gy delivered in daily 1.8-Gy fractions on 5 d a week over 5 wk)and capecitabine chemotherapy(dose:800 mg/m²twice daily throughout the duration of radiotherapy).The primary study endpoint was disease-free survival(DFS),and the secondary endpoints were overall survival(OS),toxic effects,and treatment *** The 3-year DFS and OS were 66.2%and 75%,*** median time to recurrence was 19.5 mo(range,6.1-68 mo).peritoneal implantation(n=10)was the most common recurrence pattern,and the lung was the most common site of extra-abdominal metastases(n=5).Nine patients developed grade 3 or 4 toxicities during *** patients discontinued ACRT,while eleven underwent ACRT without receiving the entire course of *** were no treatmentrelated *** The ACRT protocol described herein showed acceptable safety and efficacy for patients with locally advanced GC who received radical gastrectomy and D1/2 LND.

关键词： Gastric cancer Radiotherapy Chemoradiotherapy clinical trial Phase II