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Activin A receptor type 1C single nucleotide polymorphisms associated with esophageal squamous cell carcinoma risk in Chinese population

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 39-51页

作者： Si-Yun Lin Hou Huang Jin-Jie Yu Feng Su Tian Jiang Shao-Yuan Zhang Lu Lv Tao Long Hui-Wen Pan Jun-Qing Qi Qiang Zhou Wei-Feng Tang Guo-Wen Ding Li-Ming Wang Li-Jie Tan Jun Yin Department of Thoracic Surgery Zhongshan Hospital Affiliated to Fudan UniversityShanghai 200032China Shanghai Key Laboratory of Clinical Geriatric Medicine Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China Department of Cardiothoracic Surgery The Affiliated People's Hospital of Jiangsu UniversityZhenjiang 212002Jiangsu ProvinceChina Department of Thoracic Surgery Sichuan Cancer Hospital&InstituteChengdu 610042Sichuan ProvinceChina Department of Cardiothoracic Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210000Jiangsu ProvinceChina Department of Respiratory and Critical Care Medicine Shanghai Xuhui Central HospitalShanghai 200032China

BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and *** A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent *** To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han *** In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were *** SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction ***-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were *** Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male *** the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to *** ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.

关键词： Activin A receptor type 1C Single nucleotide polymorphisms esophageal squamous cell carcinoma Genetic susceptibility Hospital-based cohort study

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Nuclear Factor-κB Signaling Pathway Constitutively Activated in esophageal squamous cell carcinoma cell Lines and Inhibition of Growth of cells by Small Interfering RNA

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Acta Biochimica et Biophysica Sinica 2006年第5期38卷 318-326页

作者： Fang TIAN Wei-Dong ZANG Wei-Hong HOU Hong-Tao LIU Le-Xun XUE Laboratory for cell Biology,Medical College,Zhengzhou University,Zhengzhou 450052,China Laboratory for cell Biology Medical College Zhengzhou UniversityZhengzhou 450052 China

Although constitutive nuclear factor(NF)-kB activation has been reported in many humantumors,the role of the NF-kB pathway in esophageal squamous cell carcinoma(ESCC)has not been *** this study,NF-kB pathway in two ESCC cell lines was investigated using immunocytochemistry,Westernblot and reverse transciiption-polymerase chain *** activation of NF-kB DNA binding was determinedby electrophoretic mobility-shift *** interference was used to specifically inhibit the expression *** of cells Was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide *** results showed that p50,p65,IkBα,p-IkBα and IkB kinase β were expressed and mainly localized in *** transcription-polymerase chain reaction results showed the constitutive expressions ofp50,p65 and IkBα mRNA in the two ESCC cell ***,the nuclear extracts revealed that p50and p65 translocated to the nucleus had DNA-binding ***,small interfering RNA of p65 decreasedthe expression of p65,and the viability of ceils transfected with p65 small interfering RNA was significantlysuppressed at the same concentration of 5-fluorouracil(Pcell lines to 5-fluorouracil,suggesting that NF-kB might be a good target for cancer treatment.

关键词： NF-κB RNA interference esophageal squamous cell carcinoma IκBα IκBα kinase

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Enhanced Expression of miR-425 Promotes esophageal squamous cell carcinoma Tumorigenesis by Targeting SMAD2

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Journal of Genetics and Genomics 2015年第11期42卷 601-611页

作者： Lingyan Liu Zitong Zhao Wei Zhou Xinyi Fan Qimin Zhan Yongmei Song State Key Laboratory of Molecular Oncology Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical College

esophageal squamous cell carcinoma （ESCC） is one of the most common and deadly cancers in the world, Currently, clinical therapy of ESCC remains limited and the five-year survival rate is poor. The function of miR-425 has been reported in multiple human cancers. However. the tumorigenic role and clinical significance of miR-425 in ESCC remains unclear. We found that enhanced expression of miR- 425 in ESCC cell lines not only promoted cell proliferation and colony formation, but also increased cellular metastasis. Furthermore, we revealed the mechanism that miR-425 inhibited the expression of SMAD2 by targeting the second binding site in the 3＇-untranslated region （3＇-UTR） in ESCC. This mode of action influenced not only SMAD2 rnRNA expression but also protein expression. In addition, we detected the expression of miR-425 in ESCC tissues and plasma. Moreover, we analyzed the relationship between miR-425 expression and SMAD2 mRNA expression. We found that miR-425 was overexpressed in ESCC tissues and the plasma relative to adjacent normal tissues and plasma of healthy individuals. Furthermore, there was a negative correlation between miR-425 expression and SMAD2, Taken together, our results show that miR-425 functions as an oncogene by targeting the 3＇-UTR of SMAD2 and indicate the potential utility of plasma miR-425 as a novel biomarker for ESCC diagnosis.

关键词： esophageal squamous cell carcinoma miR-425 Plasma miRNA SMAD2

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Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

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Frontiers of Medicine 2023年第2期17卷 290-303页

作者： Yubing Zhou Xinyu He Yanan Jiang Zitong Wang Yin Yu Wenjie Wu Chenyang Zhang Jincheng Li Yaping Guo Xinhuan Chen Zhicai Liu Jimin Zhao Kangdong Liu Zigang Dong The Pathophysiology Department School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhou 450000China The China-US(Henan)Hormel Cancer Institute Zhengzhou 450000China State Key Laboratory of esophageal Cancer Prevention and Treatment Zhengzhou 450000China Provincial Cooperative Innovation Center for Cancer Chemoprevention Zhengzhou UniversityZhengzhou 450000China Cancer Chemoprevention International Collaboration Laboratory Zhengzhou 450000China Oncology Department The Tumor Hospital of Linzhou CityLinzhou 456500China

esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

关键词： benzydamine cyclin-dependent kinase 2 patient-derived xenograft esophageal squamous cell carcinoma

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Autoantibodies against MMP-7 as a novel diagnostic biomarker in esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2011年第10期17卷 1373-1378页

作者： Jing-Hua Zhou Bin Zhang Kemp H Kernstine Li Zhong Department of cellBiology College of Life Sciences Hebei University Baoding071400 Hebei Province China Department of Thoracic Surgery City of Hope Medical Center Duarte CA 91766 United States Department of Basic Medical Sciences College of Osteopathic Medicine Western University of Health SciencesPomona CA 91766 United States

AIM： To evaluate the diagnostic values of serum autoan tibodies against matrix metalloproteinase-7 （MMP-7） in patients with esophageal squamous cell carcinoma （ESCC）. METHODS： The MMP-7 cDNA was cloned from ESCC tissues, and MMP-7 was expressed and purified from a prokaryotic system. MMP-7 autoanUbodies were then measured in sera from 50 patients with primary ESCC and 58 risk-matched controls, using a reverse capture enzyme-linked immunosorbent assay （ELISA） in which autoantibodies to MMP-7 bound to the purified MMP-7 proteins. In addition, MMP-7 autoantibody levels in sera from 38 gastric cancer patients and from control serum samples were also tested. RESULTS： The optimum conditions for recombinant MMP-7 protein expression were determined as 0.04 mmol/L Isopropyl-13-D-Thiogalactopyranoside （IPTG）induction at 37℃ for four hours. The levels of serum autoantibodies against MMP-7 were significantly higher in patients with ESCC than in the matched-control samples （OD450 = 1.69 ±0.08 vs OD450 = 1.55 ± 0.10, P 〈 0.001）. The area under the receiver operating character- istic （ROC） curve was 0.87. The sensitivity and specificity for detection of ESCC were 78.0% and 81.0%, respectively, when the OD450 value was greater than 1.65. Although the levels of autoantibodies against MMP-7 were also significantly higher in patients with gastric cancer compared to control samples （OD450 = 1.62± 0.06 vs OD450 = 1.55±0.10, P 〈 0.001）, the diagnostic accuracy was less significant than in ESCC patients. The area of ROC curve was 0.75, whereas the sensitivity and specificity were 60.5% and 71.7%, respectively, when the cut-off value of OD450 was set at 1.60. CONCLUSION： Serum autoantibody levels of MMP-7 may be a good diagnostic biomarker for esophageal squamous cell carcinoma,

关键词： Matrix metalloproteinase-7 Serum autoantibody esophageal squamous cell carcinoma Gastriccancer Biomarker

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Overexpression of TLR3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2011年第32期17卷 3745-3751页

作者： Ilyar Sheyhidin Gulnaz Nabi Ayshamgul Hasim Rui-Ping Zhang Julaiti Ainiwaer Hong Ma Hua Wang Department of Thoracic Surgery of the First Affiliated Hospital Medical University of Xinjiang 830054 Urumqi Xinjiang China Department of Rehabilitative of the First Affiliated Hospital Medical University of Xinjiang 830054 Urumqi Xinjiang China Department of Pathology College of Basic Medicine Medical University of Xinjiang 830011 Urumqi Xinjiang China

AIM: To investigate the expression of Toll-like receptor (TLR) 3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma (ESCC). METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry were used to analyze the expression of TLR3, TLR4, TLR7 and TLR9 mRNA and protein in samples from 87 esophageal cancer patients consisting of both tumor and normal tissue. RESULTS: A significant increase in TLR3, TLR4, TLR7 and TLR9 mRNA levels was detected in ESCC samples. Tumors exhibited high TLR protein expression, (70.1%, 72.4%, 66.7% and 78.2% for TLR3, TLR4, TLR7 and TLR9, respectively, P cells (48.3%) and TLR9 expression in fibroblast-like cells (60.9%). Tumors with high TLR3 expression in tumor cells or high TLR4 expression in mononuclear inflammatory cells were significantly associated with a higher probability of lymph node metastasis and increased depth of invasion. However, tumors with high TLR9 expression in fibroblast-like cells were associated with low probabilities of invasion and metastasis. There was no significant variation between the expression of TLR3, TLR4, TLR7 and TLR9 among different ethnic groups. CONCLUSION: TLR3, TLR4, TLR7 and TLR9 expression appears important to the biological pathogenesis of ESCC. TLRs may represent therapeutic targets for ESCC.

关键词： esophageal squamous cell carcinoma Invasion Metastasis Prognosis Toll-like receptor

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Concurrent chemoradiotherapy combined with enteral nutrition support:a radical treatment strategy for esophageal squamous cell carcinoma patients with malignant istulae

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Chinese Journal of Cancer 2017年第1期36卷 26-33页

作者： Li Ma Guang-Yu Luo Yu-Feng Ren Bo Qiu Hong Yang Chun-Xia Xie Song-Ran Liu Shi-Liang Liu Zhao-Lin Chen Qun Li Jian-Hua Fu Meng-Zhong Liu Yong-Hong Hu Wen-Feng Ye Hui Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Guangdong esophageal Cancer Research Institute Department of Radiation Oncology Sun Yat-sen University Cancer Center Department of Endoscopy Sun Yat-sen University Cancer Center Department of Radiation Oncology The First Affiliated Hospital of Sun Yat-sen University Department of Thoracic Surgery Sun Yat-sen University Cancer Center Department of Clinical Nutrition Sun Yat-sen University Cancer Center

Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long?term ***: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat?sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were ret?rospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening(NRS) before, during, and after treatment. Twenty?two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of ***: With a median follow?up of 18 months(range, 3–39 months), patients' 1?year overall survival(OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score(P n NRS score(P se to treatment(P < 0.001) were sig= 0.003), increase i= 0.024), fistula closure(P = 0.011), and responnifi?cantly associated with OS. Multivariate analysis showed that tumor response(P = 0.044) and increase in NRS score(P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients(20.0%), grade 3 neutro?penia was observed in 11 patients(27.5%), and grade 3 cough was observed in 13 patients(32.5%); 2 patients(5.0%) died of massive bleeding during ***: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be

关键词： esophageal squamous cell carcinoma Malignant istula Radiotherapy Concurrent chemotherapy Enteral nutrition support

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Inhibiting autophagy enhances sulforaphane-induced apoptosis via targeting NRF2 in esophageal squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2021年第5期11卷 1246-1260页

作者： Zhaoming Lu Yandan Ren Li Yang Ang Jia Yi Hu Yu Zhao Wuduo Zhao Bin Yu Wen Zhao Jianying Zhang Guiqin Hou State Key Laboratory of esophageal Cancer Prevention&Treatment School of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China Collaborative Innovation Center of Cancer Chemoprevention Zhengzhou 450001China Center of Advanced Analysis&Gene Sequencing Zhengzhou UniversityZhengzhou 450001China Henan Academy of Medical and Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450052China Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China

Sulforaphane(SFN), a natural anti-tumor compound from cruciferous vegetables, has been reported to induce protective autophagy to cancer cells, which might impair the anti-tumor efficiency of SFN. However, the accurate function and mechanism of SFN inducing autophagy in cancers are still obscure, especially in esophageal squamous cell carcinoma(ESCC), one of malignancies with high incidence in North China. Here, we mainly explored the potential function of autophagy upon SFN treatment in ESCC and molecular mechanism. We demonstrated that SFN could inhibit cell proliferation and induce apoptosis by activating caspase pathway. Moreover, we found activation of NRF2 pathway by SFN was responsible for the induction of autophagy and also a disadvantage element to the anti-tumor effects of SFN on ESCC, indicating that SFN might induce protective autophagy in ESCC. We, therefore,investigated effects of autophagy inhibition on sensitivity of ESCC cells to SFN and found that chloroquine(CQ) could neutralize the activation of SFN on NRF2 and enhance the activation of SFN on caspase pathway, thus improved the anti-tumor efficiency of SFN on ESCC in vitro and in vivo. Our study provides a preclinical rationale for development of SFN and its analogs to the future treatment of ESCC.

关键词： Sulforaphane Autophagy Chloroquine NRF2 esophageal squamous cell carcinoma

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esophageal mycobiome landscape and interkingdom interactions in esophageal squamous cell carcinoma

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Gastroenterology Report 2023年第1期11卷 300-308页

作者： Wen-Qing Rao Zheng Lin Jian Jiang Jian-Wen Wang Zhi-Feng Lin Rong Fu Wei-Lin Chen Yuan-Mei Chen Xian-EPeng Zhi-Jian Hu Department of Epidemiology and Health Statistics Fujian Medical University Fujian Provincial Key Laboratory of Environment Factors and CancerSchool of Public HealthFujian Medical UniversityFuzhouFujianP.R.China Department of Medical Services Fujian Provincial HospitalFuzhouFujianP.R.China Department of Digestive Endoscopy Anxi County HospitalAnxiFujianP.R.China Department of Radiation Oncology Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujianP.R.China Department of Thoracic Surgery Fujian Provincial Cancer Hospital Affiliation to Fujian Medical UniversityFuzhouFujianP.R.China Key Laboratory of Ministry of Education for Gastrointestinal Cancer Fujian Medical UniversityFuzhouFujianP.R.China

Background The study purpose was to characterize the mycobiome and its associations with the expression of pathogenic genes in esophageal squamous cell carcinoma(ESCC).Methods Patients with primary ESCC were recruited from two central *** performed internal transcribed spacer 1(ITS1)ribosomal DNA sequencing *** compared differential fungi and explored the ecology of fungi and the interaction of bacteria and *** The mycobiota diversity was significantly different between tumors and tumor-adjacent *** further analysed the differences between the two groups,at the species level,confirming that Rhodotorula toruloides,Malassezia dermatis,Hanseniaspora lachancei,and Spegazzinia tessarthra were excessively colonized in the tumor samples,whereas Preussia persica,Fusarium solani,Nigrospora oryzae,Acremonium furcatum,Golovinomyces artemisiae,and Tausonia pullulans were significantlymore abundant in tumor-adjacent *** fungal co-occurrence network in tumor-adjacent samples was larger and denser than that in ***,themore complex bacterial–fungal interactions in tumor-adjacent samples were also *** expression ofmechanistic target of rapamycin kinase was positively correlated with the abundance of *** and *** in tumor-adjacent *** tumors,the expression ofMET proto-oncogene,receptor tyrosine kinase(MET)had a negative correlation and a positive correlation with the abundance of *** and ***,*** This study revealed the landscape of the esophageal mycobiome characterized by an altered fungal composition and bacterial and fungal ecology in ESCC.

关键词： esophageal squamous cell carcinoma mycobiome fungi interkingdom co-occurrence network

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Aberrant methylation of the 3q25 tumor suppressor gene PTX3 in human esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2011年第37期17卷 4225-4230页

作者： Jun-Xiong Wang Yuan-Long He Sheng-Tao Zhu Shuo Yang Shu-Tian Zhang Beijing Friendship Hospital Affiliated to the Capital Medical University Beijing 100050 China Department of Gastroenterology Qingdao Municipal Hospital Qingdao 266071 Shandong Province China Department of Gastroenterology Beijing Friendship Hospital Affiliated to the Capital Medical University Beijing 100050 China Shuo Yang Laboratory Medicine Department Peking University Third Hospital Beijing 100050 China

AIM:To identify the novel methylation-silenced gene pentraxin 3(PTX3) in esophageal squamous cell carcinoma(ESCC).METHODS:PTX3 mRNA expression was examined in six human ESCC cell lines,one human immortalized normal esophageal epithelial cell line,primary ESCC tumor tissue,and paired adjacent nontumor tissue using reverse transcription polymerase chain reaction(RTPCR).Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein *** specific PCR and bisulphite genomic sequencing were employed to investigate the methylation of the candidate ***:In the majority of ESCC cell lines,we found that PTX3 expression was down-regulated due to gene promoter hypermethylation,which was further confirmed by bisulphite genomic *** treatment with 5-aza-2'-deoxycytidine restored PTX3 mRNA expression in ESCC cell *** was more common in tumor tissues(85%) than in adjacent nontumor tissues(25%)(P < 0.01).CONCLUSION:PTX3 is down-regulated through promoter hypermethylation in ESCC,and could potentially serve as a biomarker of ESCC.

关键词： Tumor suppressor gene Pentraxin 3 Microarray DNA methylation esophageal squamous cell carcinoma

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