|
1
|
Verdelli C, Fabrizio FP, Maroni P, Morotti A, Tavanti GS, Carrara S, Guarnieri V, Cetani F, Scillitani A, Maggiore R, Perticone F, Vaira V, Muscarella LA, Corbetta S. Aberrant promoter methylation, expression and function of RASSF1A gene in a series of Italian parathyroid tumors. Endocrine 2025; 87:1246-1256. [PMID: 39607643 DOI: 10.1007/s12020-024-04113-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 11/13/2024] [Indexed: 11/29/2024]
Abstract
PURPOSE Aberrant epigenetic features are key events involved in parathyroid tumorigenesis, including DNA methylation, histone methylation, and non-coding RNAs. Ras Association Domain Family Protein1 Isoform A (RASSF1A) and Adenomatous Polyposis of Colon (APC) are frequently downregulated in human cancers. Here, we investigated their deregulated expression and the potential role in parathyroid neoplasms. METHODS methylation of RASSF1A and APC promoters was analyzed in a series of parathyroid adenomas (PAds, n = 80) and parathyroid carcinomas (PCas, n = 9) from Italian patients with primary hyperparathyroidism, RESULTS: RASSF1A and APC promoter methylation occurred in about 90% of PAds samples. PCas displayed RASSF1A promoter methylation, while APC promoter was methylated only in 2 samples. Of note, RASSF1A promoter methylation negatively correlated with PAds tumor size. However, RASSF1A transcript and protein levels were reduced in PAds and PCas compared with parathyroid normal glands. Investigating the potential mechanism involved in RASSF1A promoter methylation, we found that DNA methyltransferases (DNMTs) activity was variable in PAds and inversely correlated with RASSF1A protein levels. In addition, the RASSF1A promoter methylation negatively correlated with long-non-coding Antisense Intronic Noncoding RASSF1A (ANRASSF1A) mRNA levels, excluding the involvement of ANRASSF1 in RASSF1A regulation. In HEK293A cells transfected with the calcium sensing receptor (CASR), loss of RASSF1A increased basal phosphorylated Extracellular signal-regulated kinase (pERK/ERK) levels blunting the CASR-induced increases. CONCLUSION RASSF1A and APC promoter methylation is a hallmark of parathyroid tumors; deregulation of DNMTs activity contributes to modulation of RASSF1A expression. Loss of RASSF1A may be involved in the tuning of ERK pathway in parathyroid tumors.
Collapse
Affiliation(s)
- Chiara Verdelli
- Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy
| | - Federico Pio Fabrizio
- Laboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
- Department of Medicine and Surgery, University of Enna "Kore", 94100, Enna, Italy
| | - Paola Maroni
- Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy
| | - Annamaria Morotti
- Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Giulia Stefania Tavanti
- Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Silvia Carrara
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| | - Vito Guarnieri
- Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
| | - Filomena Cetani
- Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy
| | - Alfredo Scillitani
- Endocrine Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
| | | | | | - Valentina Vaira
- Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Lucia Anna Muscarella
- Laboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
| | - Sabrina Corbetta
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
- Bone Metabolic Diseases and Diabetes Unit, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy.
| |
Collapse
|
|
2
|
Wang W, Ye L, Li H, Mao W, Xu X. Targeting esophageal carcinoma: molecular mechanisms and clinical studies. MedComm (Beijing) 2024; 5:e782. [PMID: 39415846 PMCID: PMC11480525 DOI: 10.1002/mco2.782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 09/24/2024] [Accepted: 09/24/2024] [Indexed: 10/19/2024] Open
Abstract
Esophageal cancer (EC) is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in-depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes. Our review delves into the molecular pathology of EC, emphasizing genetic and epigenetic alterations, aberrant signaling pathways, tumor microenvironment factors, and the mechanisms of metastasis and immune evasion. We further scrutinize the current landscape of targeted therapies, including the roles of EGFR, HER2, and VEGFR, alongside the transformative impact of ICIs. The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune-mediated treatments, and introduces the burgeoning domain of antibody-drug conjugates, bispecific antibodies, and multitarget-directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations.
Collapse
Affiliation(s)
- Wenjing Wang
- Department of Medical Thoracic OncologyZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Postgraduate Training Base AllianceWenzhou Medical UniversityWenzhouZhejiangChina
| | - Lisha Ye
- Department of Medical Thoracic OncologyZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Postgraduate Training Base AllianceWenzhou Medical UniversityWenzhouZhejiangChina
| | - Huihui Li
- Department of Medical Thoracic OncologyZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Postgraduate Training Base AllianceWenzhou Medical UniversityWenzhouZhejiangChina
| | - Weimin Mao
- Postgraduate Training Base AllianceWenzhou Medical UniversityWenzhouZhejiangChina
- The Cancer Hospital of the University of Chinese Academy of Sciences, Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhouZhejiangChina
| | - Xiaoling Xu
- Postgraduate Training Base AllianceWenzhou Medical UniversityWenzhouZhejiangChina
- Department of Radiation OncologyShanghai Pulmonary Hospital, Tongji University School of MedicineShanghaiChina
| |
Collapse
|
|
3
|
Zhao YX, Zhao HP, Zhao MY, Yu Y, Qi X, Wang JH, Lv J. Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:2638-2656. [PMID: 38855150 PMCID: PMC11154680 DOI: 10.3748/wjg.v30.i20.2638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/26/2024] [Accepted: 05/13/2024] [Indexed: 05/27/2024] Open
Abstract
As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.
Collapse
Affiliation(s)
- Yi-Xin Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Meng-Yao Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Yan Yu
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Xi Qi
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Ji-Han Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, Shaanxi Province, China
| | - Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| |
Collapse
|
|
4
|
Correlation between RASSF1A Methylation in Cell-Free DNA and the Prognosis of Cancer Patients: A Systematic Review and Meta-Analysis. JOURNAL OF ONCOLOGY 2022; 2022:3458420. [PMID: 35528240 PMCID: PMC9071870 DOI: 10.1155/2022/3458420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 03/18/2022] [Accepted: 04/07/2022] [Indexed: 11/17/2022]
Abstract
Background Although the effects of methylation of the Ras association domain-containing protein 1 isoform A (RASSF1A) gene in cell-free DNA on the outcomes of patients with different types of cancer have been reported, the results are inconsistent. Objective : To explore the relationships between RASSF1A methylation in cell-free DNA and the outcomes of cancer patients. Methods The PubMed, Embase, and Web of Science databases were searched for papers related to this topic on December 8, 2021. The retrieved articles were screened by two independent researchers, following which the methodological quality of the selected studies was evaluated using the Newcastle-Ottawa Scale. Additionally, hazard ratios were calculated, and publication bias of the studies was determined using Egger's test. Results Nine relevant publications involving a combined total of 1254 patients with different types of cancer were included in this study. The combined results of the random effects models yielded a hazard ratio of 1.73 (95% confidence interval: 1.31, 2.29; P < 0.001), which suggested there was a significant association between RASSF1A methylation and overall survival, and patients with an RASSF1A methylation status had a significantly increased risk of total death. Moreover, the Egger test result suggested there was no significant publication bias among the included studies. Conclusions The methylation of RASSF1A in cell-free DNA in cancer patients was observably associated with an increased risk of poor overall survival.
Collapse
|
|
5
|
Guru SA, Sumi MP, Mir R, Beg MMA, Koner BC, Saxena A. Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival. BMC Cancer 2022; 22:405. [PMID: 35421941 PMCID: PMC9008925 DOI: 10.1186/s12885-022-09481-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 04/04/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND There is strong evidence that disease progression, drug response and overall clinical outcomes of CML disease are not only decided by BCR/ABL1 oncoprotein but depend on accumulation of additional genetic and epigenetic aberrations. DNA hydroxymethylation is implicated in the development of variety of diseases. DNA hydroxymethylation in gene promoters plays important roles in disease progression, drug response and clinical outcome of various diseases. Therefore in this study, we aimed to explore the role of aberrant hydroxymethylation in promoter regions of different tumor suppressor genes in relation to CML disease progression, response to imatinib therapy and clinical outcome. METHODS We recruited 150 CML patients at different clinical stages of the disease. Patients were followed up for 48 months and haematological/molecular responses were analysed. Haematological response was analysed by peripheral blood smear. BCR/ABL1 specific TaqMan probe based qRT-PCR was used for assessing the molecular response of CML patients on imatinib therapy. Promoter hydroxymethylation of the genes was characterized using MS-PCR. RESULTS We observed that promoter hydroxymethylation of DAPK1, RIZ1, P16INK4A, RASSF1A and p14ARFARF genes characterize advanced CML disease and poor imatinib respondents. Although, cytokine signalling (SOCS1) gene was hypermethylated in advanced stages of CML and accumulated in patients with poor imatinib response, but the differences were not statistically significant. Moreover, we found hypermethylation of p14ARF, RASSF1 and p16INK4A genes and cytokine signalling gene (SOCS1) significantly associated with poor overall survival of CML patients on imatinib therapy. The results of this study are in agreement of the role of aberrant DNA methylation of different tumor suppressor genes as potential biomarkers of CML disease progression, poor imatinib response and overall clinical outcome. CONCLUSION In this study, we report that promoter hydroxymethylation of DAPK1, RIZ1, P16INK4A, RASSF1A and p14ARFARF genes is a characteristic feature of CML disease progressions, defines poor imatinib respondents and poor overall survival of CML patients to imatinib therapy.
Collapse
MESH Headings
- Apoptosis/genetics
- Cell Cycle
- Chronic Disease
- Cytokines
- DNA/therapeutic use
- Disease Progression
- Drug Resistance, Neoplasm/genetics
- Humans
- Imatinib Mesylate/pharmacology
- Imatinib Mesylate/therapeutic use
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
- Leukemia, Myeloid
- Surveys and Questionnaires
- Tumor Suppressor Protein p14ARF/therapeutic use
Collapse
Affiliation(s)
- Sameer Ahmad Guru
- Lurie Children's Hospital and Stanley Manne Children's Research Institute, Northwestern University, Chicago, IL, USA
- Department of Biochemistry, Multidisciplinary Research Unit (MRU), Maulana Azad Medical College, New Delhi, India
| | - Mamta Pervin Sumi
- Department of Inflammation and Immunity, Lerner Research Institute, Cleve Land Clinic, OH, Cleveland, USA
| | - Rashid Mir
- Kingdom of Saudi Arabia, University of Tabuk, Tabuk, Saudi Arabia
| | - Mirza Masroor Ali Beg
- Faculty of Medicine and Center for Promotion of Medical Research, Faculty of Medical Sciences, Ala-Too International University, Bishek, Kyrgyzstan
| | - Bidhan Chandra Koner
- Department of Biochemistry, Hamdard Institute of Medical Science and Research (HIMSR), New Delhi, India
| | - Alpana Saxena
- Department of Biochemistry, Multidisciplinary Research Unit (MRU), Maulana Azad Medical College, New Delhi, India.
- Department of Biochemistry, Hamdard Institute of Medical Science and Research (HIMSR), New Delhi, India.
| |
Collapse
|
|
6
|
He Y, Yu X, Zhang M, Guo W. Pan-cancer analysis of m 5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers. World J Surg Oncol 2021; 19:224. [PMID: 34325709 PMCID: PMC8323224 DOI: 10.1186/s12957-021-02342-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 07/21/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND 5-Methylcytosine (m5C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m5C regulators and the outcomes of modified nucleobases in RNAs. METHODS Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m5C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m5C regulators and the activity of related hallmark pathways of cancers. RESULTS After validating m5C regulators' expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m5C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival. CONCLUSION Our results offered strong evidence and clinical implications for the involvement of m5C regulators.
Collapse
Affiliation(s)
- Yuting He
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450052, China.
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation At Henan Universities, Zhengzhou, 450052, China.
- Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, 450052, China.
| | - Xiao Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450052, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation At Henan Universities, Zhengzhou, 450052, China
- Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, 450052, China
| | - Menggang Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450052, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation At Henan Universities, Zhengzhou, 450052, China
- Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, 450052, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450052, China.
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation At Henan Universities, Zhengzhou, 450052, China.
- Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, 450052, China.
| |
Collapse
|
|
7
|
Yang Q, Guo X, Xu Y, Duan C, Wang H, Feng Q, Zhang N. Involvement of DNA methyltransferase 1 (DNMT1) and multidrug resistance-associated proteins in 2-methoxyestradiol-induced cytotoxicity in EC109/Taxol cells. Transl Cancer Res 2021; 10:10-21. [PMID: 35116235 PMCID: PMC8797790 DOI: 10.21037/tcr-20-2678] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 11/27/2020] [Indexed: 11/16/2022]
Abstract
BACKGROUND Due to acquired drug resistance, paclitaxel-based chemotherapy has limited clinical effects in the treatment of various tumors including esophageal cancer. This study analyzes the hypothesis that paclitaxel resistance is related to changes in the expression of DNA methyltransferase 1 (DNMT1). The thesis also studies multidrug resistance-related proteins and the mechanism underlying 2-methoxyestradiol (2-ME)-induced cytotoxicity in EC109/Taxol cells was examined. METHODS In this study, the mechanisms of 2-ME-induced cytotoxicity in EC109/Taxol cells was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, DNA ladder assay, DNMT activity assay, and Western blotting. The result of 2-ME-induced cytotoxicity EC109/Taxol cells is compared with that of EC109 parental cells. RESULTS The results show that low concentrations of 2-ME (0.5-10 µM) inhibited cell growth, with IC50 values of 2.04 and 5.38 µmol/L in EC109/Taxol cells and EC109 parental cells after 72 hours of treatment, respectively. Exposure to 2-ME could increase G2/M cell cycle arrest and could increase apoptosis more effectively in EC109/Taxol cells than that observed in the EC109 parental cells. Furthermore, it is observed that paclitaxel resistance is associated with decreased DNMT activity. This study shows that 2-ME decreases DNMT1-mediated paclitaxel resistance by simultaneously reducing the expression of ATP-binding cassette (ABC) transporters, including phosphoglycoprotein (P-gp), breast cancer resistance protein (BCRP), and multi-drug resistance protein 1 (MRP1), in EC109/Taxol cells. CONCLUSIONS In this study, the co-treatment of Taxol and 2-ME to EC109 could significantly induce cytotoxic effects, whose mechanism might be associated with DNMT1 and multidrug resistance-associated proteins.
Collapse
Affiliation(s)
- Qingqing Yang
- China School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Xiaojing Guo
- China School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Yue Xu
- China School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Chang Duan
- Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haofan Wang
- Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Quanling Feng
- Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Nan Zhang
- China School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| |
Collapse
|
|
8
|
Lin L, Cheng X, Yin D. Aberrant DNA Methylation in Esophageal Squamous Cell Carcinoma: Biological and Clinical Implications. Front Oncol 2020; 10:549850. [PMID: 33194605 PMCID: PMC7645039 DOI: 10.3389/fonc.2020.549850] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 09/18/2020] [Indexed: 12/20/2022] Open
Abstract
Almost all cancer cells possess multiple epigenetic abnormalities, which cooperate with genetic alterations to enable the acquisition of cancer hallmarks during tumorigenesis. As the most frequently found epigenetic change in human cancers, aberrant DNA methylation manifests at two major forms: global genomic DNA hypomethylation and locus-specific promoter region hypermethylation. It has been recognized as a critical contributor to esophageal squamous cell carcinoma (ESCC) malignant transformation. In ESCC, DNA methylation alterations affect genes involved in cell cycle regulation, DNA damage repair, and cancer-related signaling pathways. Aberrant DNA methylation patterns occur not only in ESCC tumors but also in precursor lesions. It adds another layer of complexity to the ESCC heterogeneity and may serve as early diagnostic, prognostic, and chemo-sensitive markers. Characterization of the DNA methylome in ESCC could help better understand its pathogenesis and develop improved therapies. We herein summarize the current research and knowledge about DNA methylation in ESCC and its clinical significance in diagnosis, prognosis, and treatment.
Collapse
Affiliation(s)
- Lehang Lin
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | | | - Dong Yin
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
9
|
Chen H, Qin Q, Xu Z, Chen T, Yao X, Xu B, Sun X. DNA methylation data-based prognosis-subtype distinctions in patients with esophageal carcinoma by bioinformatic studies. J Cell Physiol 2020; 236:2126-2138. [PMID: 32830322 DOI: 10.1002/jcp.29999] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 07/24/2020] [Indexed: 02/06/2023]
Abstract
Esophageal carcinoma (ESCA) is caused by the accumulation of genetic and epigenetic alterations in esophageal mucosa. Of note, the earliest and the most frequent molecular behavior in the complicated pathogenesis of ESCA is DNA methylation. In the present study, we downloaded data of 178 samples from The Cancer Genome Atlas (TCGA) database to explore specific DNA methylation sites that affect prognosis in ESCA patients. Consequently, we identified 1,098 CpGs that were significantly associated with patient prognosis. Hence, these CpGs were used for consensus clustering of the 178 samples into seven clusters. Specifically, the samples in each group were different in terms of age, gender, tumor stage, histological type, metastatic status, and patient prognosis. We further analyzed 1,224 genes in the corresponding promoter regions of the 1,098 methylation sites, and enriched these genes in biological pathways with close correlation to cellular metabolism, enzymatic synthesis, and mitochondrial autophagy. In addition, nine representative specific methylation sites were screened using the weighted gene coexpression network analysis. Finally, a prognostic prediction model for ESCA patients was built in both training and validation cohorts. In summary, our study revealed that classification based on specific DNA methylation sites could reflect ESCA heterogeneity and contribute to the improvement of individualized treatment and precise prognostic prediction.
Collapse
Affiliation(s)
- Hui Chen
- Department of Radiation Oncology, Nanjing Medical University First Affiliated Hospital, Jiangsu Province Hospital, Nanjing, Jiangsu, China
| | - Qin Qin
- Department of Radiation Oncology, Nanjing Medical University First Affiliated Hospital, Jiangsu Province Hospital, Nanjing, Jiangsu, China
| | - Zhipeng Xu
- Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu, China
| | - Tingting Chen
- Department of Oncology, Yangzhou University Affiliated Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China
| | - Xijuan Yao
- Department of Radiation Oncology, Nanjing Medical University First Affiliated Hospital, Jiangsu Province Hospital, Nanjing, Jiangsu, China
| | - Bing Xu
- Department of Radiation Oncology, Nanjing Medical University First Affiliated Hospital, Jiangsu Province Hospital, Nanjing, Jiangsu, China
| | - Xinchen Sun
- Department of Radiation Oncology, Nanjing Medical University First Affiliated Hospital, Jiangsu Province Hospital, Nanjing, Jiangsu, China
| |
Collapse
|
|
10
|
Ahmed AA, Adam Essa ME. Epigenetic alterations in female urogenital organs cancer: Premise, properties, and perspectives. SCIENTIFIC AFRICAN 2020. [DOI: 10.1016/j.sciaf.2020.e00318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
|
|
11
|
Yu J, Qi J, Sun X, Wang W, Wei G, Wu Y, Gao Q, Zheng J. MicroRNA‑181a promotes cell proliferation and inhibits apoptosis in gastric cancer by targeting RASSF1A. Oncol Rep 2018; 40:1959-1970. [PMID: 30106448 PMCID: PMC6111568 DOI: 10.3892/or.2018.6632] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 07/30/2018] [Indexed: 12/12/2022] Open
Abstract
MicroRNA (miR)-181a is a member of the miR-181 family that serves a key role in the pathogenesis of various cancer types. The present study aimed to investigate the interaction between miR-181a and Ras association domain family protein1 isoform A (RASSF1A), and their roles in gastric carcinogenesis. The interaction between miR-181a and RASSF1A was assessed in cell lines and cancer tissues. The direct binding of miR-181a and RASSF1A was identified using a luciferase reporting gene system. The effects of miR-181a and RASSF1A on gastric cancer cell growth, cell cycle and apoptosis were assessed with a Cell Counting Kit-8 assay and flow cytometry. The effects of miR-181a on cell division cycle 25A (CDC25A), cyclin A2, cyclin D1, p21, Bcl-2-associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) protein levels were assessed in gastric cancer cell lines. miR-181a directly interacted with the 3′-untranslated region of RASSF1A and downregulated RASSF1A protein expression. In tissues from patients with gastric cancer, the miR-181a level was significantly higher in the tumor tissues and was negatively correlated with the RASSF1A protein level. RASSF1A suppressed gastric cancer cell proliferation and G1/S transition, and promoted apoptosis; whereas miR-181a promoted cancer cell proliferation and G1/S transition, and suppressed apoptosis. RASSF1A knockdown attenuated the effects of miR-181a downregulation on cell proliferation and apoptosis. Furthermore, miR-181a upregulated CDC25A, cyclin A2 and Bcl-2, and downregulated Bax protein expression in gastric cancer cell lines. These data indicate that miR-181a promotes gastric carcinogenesis, possibly through a direct interaction with RASSF1A.
Collapse
Affiliation(s)
- Junhui Yu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Jie Qi
- Second Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
| | - Xuejun Sun
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Wei Wang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Guangbing Wei
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Yunhua Wu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Qi Gao
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Jianbao Zheng
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| |
Collapse
|
|
12
|
Bai J, Zhang X, Hu K, Liu B, Wang H, Li A, Lin F, Zhang L, Sun X, Du Z, Song J. Silencing DNA methyltransferase 1 (DNMT1) inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK. Oncotarget 2018; 7:44129-44141. [PMID: 27286455 PMCID: PMC5190084 DOI: 10.18632/oncotarget.9866] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Accepted: 03/31/2016] [Indexed: 11/25/2022] Open
Abstract
Our previous study showed DNMT1 is up-regulated in esophageal squamous cell carcinoma (ESCC), which is associated with methylation of tumor suppressors. In the current study, we investigate the role of DNMT1 in ESCC. We found silencing DNMT1 inhibited proliferation, metastasis and invasion of three different ESCC cells, K150, K410 and K450. We also found silencing DNMT1 induced G1 arrest and cell apoptosis in K150, K410 and K450 cells. In vivo study showed silencing DNMT1 suppressed tumor growth in nude mice. In addition, silencing DNMT1 increased expression of tumor suppressor genes, RASSF1A and DAPK, in ESCC cells and ESCC xenograft in nude mice. Moreover, silencing DNMT1 decreased methylation in promoter of RASSF1A and DAPK. In conclusion, our data demonstrated that silencing DNMT1 inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK.
Collapse
Affiliation(s)
- Jian Bai
- Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Xue Zhang
- Department of ICU, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Kai Hu
- Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Bangqing Liu
- Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Haiyong Wang
- Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Angui Li
- Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Feng Lin
- Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Lifei Zhang
- Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Xiaolin Sun
- Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Zhenzong Du
- Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.,Current address: Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Lingui District, Guilin, China
| | - Jianfei Song
- Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.,Current address: Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Lingui District, Guilin, China
| |
Collapse
|
|
13
|
Sun X, Yuan W, Hao F, Zhuang W. Promoter Methylation of RASSF1A indicates Prognosis for Patients with Stage II and III Colorectal Cancer Treated with Oxaliplatin-Based Chemotherapy. Med Sci Monit 2017; 23:5389-5395. [PMID: 29128865 PMCID: PMC5697441 DOI: 10.12659/msm.903927] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Background The purpose of this study was to investigate the prognostic significance of methylation of RAS association domain family protein 1 (RASSF1A) in the promoter region for patients with stage II and III colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy. Material/Methods There were 108 eligible CRC patients and 78 healthy controls included in this study. Methylation-specific polymerase chain reaction (MSP) was applied to detect the methylation status of RASSF1A in patients before and after chemotherapy. The effects of RASSF1A methylation on chemotherapy-sensitivity and prognosis for patients were also evaluated in the present study. Results The frequency of RASSF1A methylation was higher in CRC patients than in the healthy controls (48.44% versus 5.13%, p<0.001). After two cycles of chemotherapy, methylation ratio was significantly decreased (21.30%, p<0.001). Promoter methylation of RASSF1A was significantly correlated with tumor stage and pathological differentiation (p=0.008 and p=0.007, respectively). Patients without methylation had a favorable objective response (OR), compared with those with methylation (53.33% versus 25%, p=0.014). Methylation status of RASSF1A could influence progression-free survival and overall survival (log rank test, p<0.05). Cox regression analysis indicated that RASSF1A methylation (HR=2.471, 95% CI=1.125–5.428, p=0.024) and OR (HR=2.678, 95% CI=1.085–6.610, p 0.033) were independently correlated with prognosis for patients treated with oxaliplatin-based chemotherapy. Conclusions Promoter methylation of RASSF1A can influence sensitivity to oxaliplatin-based chemotherapy, which can be used to predict outcomes for patients with stage II and III CRC. In addition, the aberrant methylation may be a promising target for improving chemotherapy efficacy.
Collapse
Affiliation(s)
- Xicai Sun
- Department of Health Management, Weifang People's Hospital, Weifang, Shandong, China (mainland)
| | - Wei Yuan
- Department of Radiotherapy, Weifang People's Hospital, Weifang, Shandong, China (mainland)
| | - Furong Hao
- Department of Radiotherapy, Weifang People's Hospital, Weifang, Shandong, China (mainland)
| | - Wenzhen Zhuang
- Medical Record Management Section, Weifang People's Hospital, Weifang, Shandong, China (mainland)
| |
Collapse
|
|
14
|
Bai J, Zhang X, Liu B, Wang H, Du Z, Song J. Silencing DNA methyltransferase 1 leads to the activation of the esophageal suppressor gene p16 in vitro and in vivo. Oncol Lett 2017; 14:3077-3081. [PMID: 28927055 DOI: 10.3892/ol.2017.6535] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Accepted: 11/25/2017] [Indexed: 11/06/2022] Open
Abstract
Previous studies have demonstrated that DNA methyltransferase 1 (DNMT1) is required for the maintenance of DNA methylation and epigenetic changes that may lead to the development of esophageal squamous cell carcinoma (ESCC). In order to investigate whether the silencing of DNMT1 protects tumor suppressor genes, including p16, and is able to be used as a potential therapy for human ESCC, short hairpin RNA targeting DNMT1 (shRNA-DNMT1) was synthesized and transfected into the human ESCC lines KYSE150 and KYSE410, which were then injected into the backs of nude mice prior to harvesting. Results from the reverse transcription-quantitative polymerase chain reaction (PCR) and western blotting demonstrated that p16 mRNA expression was increased in the shRNA-DNMT1-transfected ESCC cell lines in vitro and in vivo. Consistent with the immunohistochemistry results, p16 was expressed in tumor tissue from nude mice that had been transplanted with the modified human ESCC lines. It was also observed that p16 methylation was inhibited following transfection with shRNA-DNMT1 as detected using methylation-specific PCR analysis. The results of the present study suggest that silencing DNMT1 serves a protective role through the demethylation and subsequent activation of p16 in vitro and in vivo.
Collapse
Affiliation(s)
- Jian Bai
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710000, P.R. China
| | - Xue Zhang
- Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710000, P.R. China
| | - Bangqing Liu
- Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang 541100, P.R. China
| | - Haiyong Wang
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang 541001, P.R. China
| | - Zhenzong Du
- Department of Thoracic Surgery, Nanxi Shan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi Zhuang 541002, P.R. China
| | - Jianfei Song
- Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang 541100, P.R. China
| |
Collapse
|
|
15
|
Wu D, Chen X, Xu Y, Wang H, Yu G, Jiang L, Hong Q, Duan S. Prognostic value of MLH1 promoter methylation in male patients with esophageal squamous cell carcinoma. Oncol Lett 2017; 13:2745-2750. [PMID: 28454461 DOI: 10.3892/ol.2017.5759] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2015] [Accepted: 01/06/2017] [Indexed: 10/20/2022] Open
Abstract
The DNA mismatch repair (MMR) gene MutL homolog 1 (MLH1) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC.
Collapse
Affiliation(s)
- Dongping Wu
- Department of Medical Oncology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Zhejiang 312000, P.R. China
| | - Xiaoying Chen
- Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Yan Xu
- Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Haiyong Wang
- Thoracic Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Zhejiang 312000. P.R. China
| | - Guangmao Yu
- Thoracic Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Zhejiang 312000. P.R. China
| | - Luping Jiang
- Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Qingxiao Hong
- Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Shiwei Duan
- Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| |
Collapse
|
|
16
|
Ma K, Cao B, Guo M. The detective, prognostic, and predictive value of DNA methylation in human esophageal squamous cell carcinoma. Clin Epigenetics 2016; 8:43. [PMID: 27110300 PMCID: PMC4840959 DOI: 10.1186/s13148-016-0210-9] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 04/14/2016] [Indexed: 12/17/2022] Open
Abstract
Esophageal cancer is one of the most common malignancies in the world. Squamous cell carcinoma accounts for approximately 90 % of esophageal cancer cases. Genetic and epigenetic changes have been found to accumulate during the development of various cancers, including esophageal squamous carcinoma (ESCC). Tobacco smoking and alcohol consumption are two major risk factors for ESCC, and both tobacco and alcohol were found to induce methylation changes in ESCC. Growing evidence demonstrates that aberrant epigenetic changes play important roles in the multiple-step processes of carcinogenesis and tumor progression. DNA methylation may occur in the key components of cancer-related signaling pathways. Aberrant DNA methylation affects genes involved in cell cycle, DNA damage repair, Wnt, TGF-β, and NF-κB signaling pathways, including P16, MGMT, SFRP2, DACH1, and ZNF382. Certain genes methylated in precursor lesions of the esophagus demonstrate that DNA methylation may serve as esophageal cancer early detection marker, such as methylation of HIN1, TFPI-2, DACH1, and SOX17. CHFR methylation is a late stage event in ESCC and is a sensitive marker for taxanes in human ESCC. FHIT methylation is associated with poor prognosis in ESCC. Aberrant DNA methylation changes may serve as diagnostic, prognostic, and chemo-sensitive markers. Characterization of the DNA methylome in ESCC will help to better understand its mechanisms and develop improved therapies.
Collapse
Affiliation(s)
- Kai Ma
- />Department of Thoracic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Baoping Cao
- />Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing, 100853 China
| | - Mingzhou Guo
- />Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing, 100853 China
| |
Collapse
|