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1
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Liatsou E, Bellos I, Katsaros I, Michailidou S, Karela NR, Mantziari S, Rouvelas I, Schizas D. Sex differences in survival following surgery for esophageal cancer: A systematic review and meta-analysis. Dis Esophagus 2024; 37:doae063. [PMID: 39137391 DOI: 10.1093/dote/doae063] [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: 03/26/2024] [Revised: 06/25/2024] [Accepted: 08/03/2024] [Indexed: 08/15/2024]
Abstract
The impact of sex on the prognosis of patients with esophageal cancer remains unclear. Evidence supports that sex- based disparities in esophageal cancer survival could be attributed to sex- specific risk exposures, such as age at diagnosis, race, socioeconomic status, smoking, drinking, and histological type. The aim of our study is to investigate the role of sex disparities in survival of patients who underwent surgery for esophageal cancer. A systematic review and meta-analysis of the existing literature in PubMed, EMBASE, and CENTRAL from December 1966 to February 2023, was held. Studies that reported sex-related differences in survival outcomes of patients who underwent esophagectomy for esophageal cancer were identified. A total of 314 studies were included in the quantitative analysis. Statistically significant results derived from 1-year and 2-year overall survival pooled analysis with Relative Risk (RR) 0.93 (95% Confidence Interval (CI): 0.90-0.97, I2 = 52.00) and 0.90 (95% CI: 0.85-0.95, I2 = 0.00), respectively (RR < 1 = favorable for men). In the postoperative complications analysis, statistically significant results concerned anastomotic leak and heart complications, RR: 1.08 (95% CI: 1.01-1.16) and 0.62 (95% CI: 0.52-0.75), respectively. Subgroup analysis was performed among studies with <200 and > 200 patients, histology types, study continent and publication year. Overall, sex tends to be an independent prognostic factor for esophageal carcinoma. However, unanimous results seem rather obscure when multivariable analysis and subgroup analysis occurred. More prospective studies and gender-specific protocols should be conducted to better understand the modifying role of sex in esophageal cancer prognosis.
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Affiliation(s)
- Efstathia Liatsou
- Department of Clinical Therapeutics, Alexandra General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Ioannis Bellos
- Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Medical School, Athens, Greece
| | - Ioannis Katsaros
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Styliani Michailidou
- First Department of Paediatric Surgery, Panagiotis & Aglaia Kyriakou Children's Hospital, Athens, Greece
| | - Nina-Rafailia Karela
- Second Department of Internal Medicine, Elpis General Hospital of Athens, Athens, Greece
| | - Styliani Mantziari
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland
| | - Ioannis Rouvelas
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Department of Upper Abdominal Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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Gao S, Wang Y, Huang M, Guo J, Wu Z, Li J. Knockdown of Gas6 Exerts Anti-Esophageal Cancer Effects by Inhibiting the PI3K/AKT Pathway. Curr Issues Mol Biol 2024; 46:11349-11358. [PMID: 39451556 PMCID: PMC11506498 DOI: 10.3390/cimb46100676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 10/06/2024] [Accepted: 10/11/2024] [Indexed: 10/26/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the digestive tract with strong migratory and invasive abilities. Gas6 is closely associated with the progression of many malignant tumors; however, the role of Gas6 in the progression of esophageal cancer is unclear. Here, we report that the knockdown of Gas6 inhibited esophageal cancer cell proliferation, migration, and invasion. In addition, Gas6 knockdown downregulated the levels of P-PI3K and P-AKT. Taken together, the findings confirm that Gas6 knockdown can inhibit esophageal cancer progression and can exert anti-tumor effects on esophageal cancer through the PI3K/AKT pathway.
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Affiliation(s)
- Shuang Gao
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; (S.G.); (Y.W.); (M.H.); (J.G.)
- Institute of Integrated Traditional Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
| | - Yu Wang
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; (S.G.); (Y.W.); (M.H.); (J.G.)
- Institute of Integrated Traditional Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
| | - Ming Huang
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; (S.G.); (Y.W.); (M.H.); (J.G.)
- Institute of Integrated Traditional Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
| | - Jianxin Guo
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; (S.G.); (Y.W.); (M.H.); (J.G.)
| | - Zhongbing Wu
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; (S.G.); (Y.W.); (M.H.); (J.G.)
| | - Jing Li
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; (S.G.); (Y.W.); (M.H.); (J.G.)
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Gao L, Li L, Zhang D, Qiu J, Qian J, Liu H. TAPI-1 Exhibits Anti-tumor Efficacy in Human Esophageal Squamous Cell Carcinoma Cells via Suppression of NF-κB Signaling Pathway. Dig Dis Sci 2024; 69:81-94. [PMID: 38007701 PMCID: PMC10787672 DOI: 10.1007/s10620-023-08181-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 11/02/2023] [Indexed: 11/28/2023]
Abstract
BACKGROUND TNF-α processing inhibitor-1 (TAPI-1) is a known metalloproteinase inhibitor with potential anti-inflammatory effects. However, its anti-cancer effects on esophageal squamous cell carcinoma (ESCC) have not been uncovered. AIM In the present study, the effects of TAPI-1 on ESCC cell viability, migration, invasion, and cisplatin resistance and the underlying molecular mechanisms were investigated in TE-1 and Eca109 cells. METHODS To this end, TE-1 and Eca109 cells were exposed to TAPI-1 for indicated time intervals. Cell viability was assessed using cell counting kit-8 assay and apoptosis was evaluated using flow cytometry assay. Migration and invasion were assessed using Transwell assays. Gene expressions were analyzed using quantitative reverse transcription polymerase chain reaction. The activation of NF-κB signaling pathway was elucidated via Western blot and chromatin immunoprecipitation assay. RESULTS We observed that higher doses (10, 20 μM) of TAPI-1 inhibited ESCC cell viability, while a lower dose (5 μM) of TAPI-1 inhibited ESCC cell migration and invasion and enhanced the chemosensitivity of ESCC cells to cisplatin. Moreover, TAPI-1 suppressed the activation of NF-κB signaling and the target genes expression in the stage of transcription initiation. Furthermore, blocking NF-κB signaling in advance could abolish all the effects of TAPI-1 on ESCC cells. CONCLUSION Overall, these results indicated that TAPI-1 impairs ESCC cell viability, migration, and invasion and facilitates cisplatin-induced apoptosis via suppression of NF-κB signaling pathway. TAPI-1 may serve as a potential adjuvant agent with cisplatin for ESCC therapy.
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Affiliation(s)
- Lin Gao
- Medical Research Center, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, 226001, People's Republic of China
| | - Li Li
- Department of Pathology, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Shengli Road No. 666, Nantong, 226001, Jiangsu, People's Republic of China
| | - Dongmei Zhang
- Medical Research Center, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, 226001, People's Republic of China
| | - Jianwei Qiu
- Department of Gastroenterology, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, 226001, People's Republic of China
| | - Junbo Qian
- Department of Gastroenterology, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, 226001, People's Republic of China
| | - Hongbin Liu
- Department of Pathology, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Shengli Road No. 666, Nantong, 226001, Jiangsu, People's Republic of China.
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4
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Liu J, Niu Y, Zhang B, Sun Q, Li H, Bai L, Su Z. Different Expression Pattern of G Protein-Coupled Estrogen Receptor GPER1 in Esophageal Squamous Cell Carcinoma and Adenocarcinoma. Int J Mol Sci 2023; 24:14055. [PMID: 37762356 PMCID: PMC10531045 DOI: 10.3390/ijms241814055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 09/08/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
Esophageal carcinoma is a male-dominant malignancy worldwide, and esophageal adenocarcinoma (EAC) shows more significant sex bias than esophageal squamous cell carcinoma (ESCC) in morbidity and mortality. The G protein-coupled estrogen receptor 1 (GPER1) is involved in several sex-related cancers; however, its expression level in esophageal carcinoma has been poorly investigated and its role is not precisely defined, depending on histological types. In the present study, the mRNA levels of GPER1 in esophageal carcinoma were collected from GEPIA and Oncomine databases for meta-analyses. The protein expression levels of GPER1 were detected by immunohistochemistry in the tissue microarray of EAC and ESCC. The GPER1 selective agonist G1, antagonist G15, and siRNA were applied in vitro to investigate their impacts on esophageal cell lines. Analysis of the RNA levels from the databases showed a decreased expression of GPER1 in overall esophageal carcinoma, and low expression levels of GPER1 were found to be associated with low survival of tumor patients. However, in the subgroup of EAC and its precancerous lesion, Barrett's esophagus, overexpression of GPER1 RNA was increased when compared with the normal tissues. The average staining scores of GPER1 protein in the tissue microarray of EAC were significantly higher than normal esophageal samples, and the rate of positive staining increased with the grade of poor tumor differentiation. The scores of GPER1 protein in ESCC tissues were lower than those in the normal tissues. The results from cell line experiments in vitro showed that the GPER1 agonist G1 inhibited proliferation and promoted apoptosis of ESCC cells EC109 with positive expression of GPER1. G1 had no obvious effect on normal esophageal NE2 cells with weak expression of GPER1. In addition, GPER1 RNA knockdown and application of antagonist G15 reversed the effects of G1 on EC109. The results of this study indicate that the expression levels of GPER1 are higher in EAC than in ESCC, which might be correlated with the dimorphic estrogen signaling pathway in different types of esophageal carcinoma.
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Affiliation(s)
- Jingshi Liu
- Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China
| | - Yongdong Niu
- Department of Pharmacology, Shantou University Medical College, Shantou 515041, China
| | - Bin Zhang
- Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China
| | - Qisi Sun
- Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China
| | - Haiyi Li
- Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China
| | - Lu Bai
- Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China
| | - Zhongjing Su
- Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China
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Uno K, Koike T, Hatta W, Saito M, Tanabe M, Masamune A. Development of Advanced Imaging and Molecular Imaging for Barrett's Neoplasia. Diagnostics (Basel) 2022; 12:2437. [PMID: 36292126 PMCID: PMC9600913 DOI: 10.3390/diagnostics12102437] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 10/04/2022] [Indexed: 11/17/2022] Open
Abstract
Barrett esophagus (BE) is a precursor to a life-threatening esophageal adenocarcinoma (EAC). Surveillance endoscopy with random biopsies is recommended for early intervention against EAC, but its adherence in the clinical setting is poor. Dysplastic lesions with flat architecture and patchy distribution in BE are hardly detected by high-resolution endoscopy, and the surveillance protocol entails issues of time and labor and suboptimal interobserver agreement for diagnosing dysplasia. Therefore, the development of advanced imaging technologies is necessary for Barrett's surveillance. Recently, non-endoscopic or endoscopic technologies, such as cytosponge, endocytoscopy, confocal laser endomicroscopy, autofluorescence imaging, and optical coherence tomography/volumetric laser endomicroscopy, were developed, but most of them are not clinically available due to the limited view field, expense of the equipment, and significant time for the learning curve. Another strategy is focused on the development of molecular biomarkers, which are also not ready to use. However, a combination of advanced imaging techniques together with specific biomarkers is expected to identify morphological abnormalities and biological disorders at an early stage in the surveillance. Here, we review recent developments in advanced imaging and molecular imaging for Barrett's neoplasia. Further developments in multiple biomarker panels specific for Barrett's HGD/EAC include wide-field imaging systems for targeting 'red flags', a high-resolution imaging system for optical biopsy, and a computer-aided diagnosis system with artificial intelligence, all of which enable a real-time and accurate diagnosis of dysplastic BE in Barrett's surveillance and provide information for precision medicine.
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Affiliation(s)
- Kaname Uno
- Division of Gastroenterology, Tohoku University Hospital, Sendai 981-8574, Japan
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Zhao X, Gabriëls RY, Hooghiemstra WTR, Koller M, Meersma GJ, Buist-Homan M, Visser L, Robinson DJ, Tenditnaya A, Gorpas D, Ntziachristos V, Karrenbeld A, Kats-Ugurlu G, Fehrmann RSN, Nagengast WB. Validation of Novel Molecular Imaging Targets Identified by Functional Genomic mRNA Profiling to Detect Dysplasia in Barrett's Esophagus. Cancers (Basel) 2022; 14:cancers14102462. [PMID: 35626066 PMCID: PMC9139936 DOI: 10.3390/cancers14102462] [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: 04/06/2022] [Revised: 05/06/2022] [Accepted: 05/13/2022] [Indexed: 02/01/2023] Open
Abstract
Barrett’s esophagus (BE) is the precursor of esophageal adenocarcinoma (EAC). Dysplastic BE (DBE) has a higher progression risk to EAC compared to non-dysplastic BE (NDBE). However, the miss rates for the endoscopic detection of DBE remain high. Fluorescence molecular endoscopy (FME) can detect DBE and mucosal EAC by highlighting the tumor-specific expression of proteins. This study aimed to identify target proteins suitable for FME. Publicly available RNA expression profiles of EAC and NDBE were corrected by functional genomic mRNA (FGmRNA) profiling. Following a class comparison between FGmRNA profiles of EAC and NDBE, predicted, significantly upregulated genes in EAC were prioritized by a literature search. Protein expression of prioritized genes was validated by immunohistochemistry (IHC) on DBE and NDBE tissues. Near-infrared fluorescent tracers targeting the proteins were developed and evaluated ex vivo on fresh human specimens. In total, 1976 overexpressed genes were identified in EAC (n = 64) compared to NDBE (n = 66) at RNA level. Prioritization and IHC validation revealed SPARC, SULF1, PKCι, and DDR1 (all p < 0.0001) as the most attractive imaging protein targets for DBE detection. Newly developed tracers SULF1-800CW and SPARC-800CW both showed higher fluorescence intensity in DBE tissue compared to paired non-dysplastic tissue. This study identified SPARC, SULF1, PKCι, and DDR1 as promising targets for FME to differentiate DBE from NDBE tissue, for which SULF1-800CW and SPARC-800CW were successfully ex vivo evaluated. Clinical studies should further validate these findings.
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Affiliation(s)
- Xiaojuan Zhao
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (X.Z.); (R.Y.G.); (W.T.R.H.); (G.J.M.); (M.B.-H.)
- Cancer Research Center Groningen, Department of Medical Oncology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
| | - Ruben Y. Gabriëls
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (X.Z.); (R.Y.G.); (W.T.R.H.); (G.J.M.); (M.B.-H.)
| | - Wouter T. R. Hooghiemstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (X.Z.); (R.Y.G.); (W.T.R.H.); (G.J.M.); (M.B.-H.)
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
| | - Marjory Koller
- Department of Surgery, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
| | - Gert Jan Meersma
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (X.Z.); (R.Y.G.); (W.T.R.H.); (G.J.M.); (M.B.-H.)
- Cancer Research Center Groningen, Department of Medical Oncology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
| | - Manon Buist-Homan
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (X.Z.); (R.Y.G.); (W.T.R.H.); (G.J.M.); (M.B.-H.)
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
| | - Lydia Visser
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (L.V.); (A.K.); (G.K.-U.)
| | - Dominic J. Robinson
- Center for Optic Diagnostics and Therapy, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands;
| | - Anna Tenditnaya
- Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, 80333 Munich, Germany; (A.T.); (D.G.); (V.N.)
- Institute of Biological and Medical Imaging, Helmholtz Zentrum München (GmbH), 85764 Neuherberg, Germany
| | - Dimitris Gorpas
- Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, 80333 Munich, Germany; (A.T.); (D.G.); (V.N.)
- Institute of Biological and Medical Imaging, Helmholtz Zentrum München (GmbH), 85764 Neuherberg, Germany
| | - Vasilis Ntziachristos
- Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, 80333 Munich, Germany; (A.T.); (D.G.); (V.N.)
- Institute of Biological and Medical Imaging, Helmholtz Zentrum München (GmbH), 85764 Neuherberg, Germany
| | - Arend Karrenbeld
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (L.V.); (A.K.); (G.K.-U.)
| | - Gursah Kats-Ugurlu
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (L.V.); (A.K.); (G.K.-U.)
| | - Rudolf S. N. Fehrmann
- Cancer Research Center Groningen, Department of Medical Oncology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
| | - Wouter B. Nagengast
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (X.Z.); (R.Y.G.); (W.T.R.H.); (G.J.M.); (M.B.-H.)
- Correspondence: ; Tel.: +31-(50)-361-6161
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Crull DJ, Hogenes MCH, Hoekstra R, Hendriksen EM, van Det MJ, Kouwenhoven EA. The Impact of Tumor Regression on Prognosis After Neoadjuvant Chemoradiotherapy in Surgically Treated Esophageal Adenocarcinoma. Ann Surg Oncol 2022; 29:3658-3666. [DOI: 10.1245/s10434-022-11336-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 12/18/2021] [Indexed: 12/24/2022]
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8
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PET imaging of esophageal cancer. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00127-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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9
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Li JH, Forghani R, Bure L, Wojtkiewicz GR, Wu Y, Iwamoto Y, Ali M, Li A, Wang C, Motlagh NJ, Papadakis AI, Pusztaszeri MP, Spatz A, Curtin H, Cheng YS, Chen JW. Molecular immuno-imaging improves tumor detection in head and neck cancer. FASEB J 2022; 36:e22092. [PMID: 34919761 PMCID: PMC9584652 DOI: 10.1096/fj.202100864r] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 11/05/2021] [Accepted: 11/23/2021] [Indexed: 01/03/2023]
Abstract
Detection and accurate delineation of tumor is important for the management of head and neck squamous cell carcinoma (HNSCC) but is challenging with current imaging techniques. In this study, we evaluated whether molecular immuno-imaging targeting myeloperoxidase (MPO) activity, an oxidative enzyme secreted by many myeloid innate immune cells, would be superior in detecting tumor extent compared to conventional contrast agent (DTPA-Gd) in a carcinogen-induced immunocompetent HNSCC murine model and corroborated in human surgical specimens. In C57BL/6 mice given 4-nitroquinoline-N-oxide (4-NQO), there was increased MPO activity in the head and neck region as detected by luminol bioluminescence compared to that of the control group. On magnetic resonance imaging, the mean enhancing volume detected by the MPO-targeting agent (MPO-Gd) was higher than that by the conventional agent DTPA-Gd. The tumor volume detected by MPO-Gd strongly correlated with tumor size on histology, and higher MPO-Gd signal corresponded to larger tumor size found by imaging and histology. On the contrary, the tumor volume detected by DTPA-Gd did not correlate as well with tumor size on histology. Importantly, MPO-Gd imaging detected areas not visualized with DTPA-Gd imaging that were confirmed histopathologically to represent early tumor. In human specimens, MPO was similarly associated with tumors, especially at the tumor margins. Thus, molecular immuno-imaging targeting MPO not only detects oxidative immune response in HNSCC, but can better detect and delineate tumor extent than nonselective imaging agents. Thus, our findings revealed that MPO imaging could improve tumor resection as well as be a useful imaging biomarker for tumor progression, and potentially improve clinical management of HNSCC once translated.
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Affiliation(s)
- Jing-Hui Li
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Department of Magnetic Resonance Imaging, FuWai Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China
| | - Reza Forghani
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Augmented Intelligence & Precision Health Laboratory (AIPHL), Department of Radiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada
| | - Lionel Bure
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Gregory R. Wojtkiewicz
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Yue Wu
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Yoshiko Iwamoto
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Muhammad Ali
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Anning Li
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Cuihua Wang
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Negin Jalali Motlagh
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Andreas I. Papadakis
- Department of Pathology, Jewish General Hospital & McGill University, Montreal, Quebec, Canada
| | - Marc P. Pusztaszeri
- Department of Pathology, Jewish General Hospital & McGill University, Montreal, Quebec, Canada
| | - Alan Spatz
- Department of Pathology, Jewish General Hospital & McGill University, Montreal, Quebec, Canada
| | - Hugh Curtin
- Department of Radiology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
| | - Ying-Sheng Cheng
- Department of Radiology, The Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University, Shanghai, China
| | - John W. Chen
- Institute for Innovation in Imaging, Department of Radiology, and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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10
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Wang H, Yang X, Sun G, Yang Q, Cui C, Wang X, Ye H, Dai L, Shi J, Zhang J, Wang P. Identification and Evaluation of Autoantibody to a Novel Tumor-Associated Antigen GNA11 as a Biomarker in Esophageal Squamous Cell Carcinoma. Front Oncol 2021; 11:661043. [PMID: 34568004 PMCID: PMC8462091 DOI: 10.3389/fonc.2021.661043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 08/18/2021] [Indexed: 12/15/2022] Open
Abstract
The study aims to explore the diagnostic value of anti-GNA11 autoantibody in esophageal squamous cell carcinoma (ESCC) from multiple levels. Autoantibody against GNA11 with the highest diagnostic performance was screened out from the customized protein microarray. A total of 486 subjects including ESCC patients and matched normal controls were recruited in the verification and validation phases by using enzyme-linked immunosorbent assay (ELISA). Western blotting analysis was used to verify the ELISA results. Immunohistochemistry (IHC) was used to evaluate GNA11 expression in ESCC tissues and para-tumor tissues. In addition, a bioinformatics approach was adopted to investigate the mRNA expression of GNA11 in ESCC. Results indicated that the level of anti-GNA11 autoantibody in ESCC patients was significantly higher than that in the normal controls, and it can be used to distinguish ESCC patients from normal individuals in clinical subgroups (p < 0.05), as revealed by both ELISA and Western blotting. The receiver operating characteristic (ROC) curve analysis showed that anti-GNA11 autoantibody could distinguish ESCC patients from normal controls with an area under the ROC curve (AUC) of 0.653, sensitivity of 10.96%, and specificity of 98.63% in the verification cohort and with an AUC of 0.751, sensitivity of 38.24%, and specificity of 88.82% in the validation cohort. IHC manifested that the expression of GNA11 can differentiate ESCC tissues with para-tumor tissues (p < 0.05), but it cannot be used to differentiate different pathological grades and clinical stages (p > 0.05). The mRNA expression of GNA11 in ESCC patients and normal controls was different with a bioinformatics mining with The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data in Gene Expression Profiling Interactive Analysis (GEPIA). In summary, anti-GNA11 autoantibody has the potential to be a new serological marker in the diagnosis of ESCC.
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Affiliation(s)
- Huimin Wang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xiaoang Yang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China
| | - Guiying Sun
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Qian Yang
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Chi Cui
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Xiao Wang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Hua Ye
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Liping Dai
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Jianxiang Shi
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Jianying Zhang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Peng Wang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
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11
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Hu X, Wang M, Cao L, Cong L, Gao Y, Lu J, Feng J, Shen B, Liu D. miR-4319 Suppresses the Growth of Esophageal Squamous Cell Carcinoma Via Targeting NLRC5. Curr Mol Pharmacol 2021; 13:144-149. [PMID: 31746301 DOI: 10.2174/1874467212666191119094636] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 11/08/2019] [Accepted: 11/11/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND The functions of microRNAs (miRNAs) in cancer progression have been recognized in recent years. However, the role of miR-4319 in esophageal squamous cell carcinoma (ESCC) remains unclear. OBJECTIVE We aimed to investigate the biological roles of miR-4319 in ESCC progression and the associated mechanisms. METHODS Real-time PCR was performed to examine the levels of miR-4319 in ESCC cell lines. The effects of miR-4319 and NOD-like receptor (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5 (NLRC5) on cell proliferation and cell cycle progression were evaluated using MTT assay, colony formation and flow cytometry assays. Bioinformatics techniques and luciferase reporter assay were applied to validate NLRC5 as a miR-4319 target. RESULTS The miR-4319 expression was lower in ESCC cells than in the normal cell line. The expression of miR-4319 repressed cell growth and induced cell cycle arrest. NLRC5 was validated as a direct downstream target of miR-4319. Overexpression of NLRC5 potentiated the effects of miR-4319 on cell growth and cell cycle distribution. CONCLUSION Our results demonstrated that miR-4319 might function as a tumor suppressor by targeting NLRC5 in ESCC.
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Affiliation(s)
- Xiao Hu
- Department of Oncology, Suqian First Hospital, Suqian, 223800, China
| | - Min Wang
- The Pain Clinic, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
| | - Lei Cao
- Department of Oncology, Suqian First Hospital, Suqian, 223800, China
| | - Li Cong
- Department of Oncology, Suqian First Hospital, Suqian, 223800, China
| | - Yujie Gao
- Department of Oncology, Suqian First Hospital, Suqian, 223800, China
| | - Jianwei Lu
- Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
| | - Jifeng Feng
- Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
| | - Bo Shen
- Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
| | - Delin Liu
- Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
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12
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Jia X, Huang C, Hu Y, Wu Q, Liu F, Nie W, Chen H, Li X, Dong Z, Liu K. Cirsiliol targets tyrosine kinase 2 to inhibit esophageal squamous cell carcinoma growth in vitro and in vivo. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:105. [PMID: 33731185 PMCID: PMC7972218 DOI: 10.1186/s13046-021-01903-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 03/08/2021] [Indexed: 12/19/2022]
Abstract
Background Esophageal squamous cell carcinoma (ESCC) is an aggressive and lethal cancer with a low 5 year survival rate. Identification of new therapeutic targets and its inhibitors remain essential for ESCC prevention and treatment. Methods TYK2 protein levels were checked by immunohistochemistry. The function of TYK2 in cell proliferation was investigated by MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and anchorage-independent cell growth. Computer docking, pull-down assay, surface plasmon resonance, and kinase assay were used to confirm the binding and inhibition of TYK2 by cirsiliol. Cell proliferation, western blot and patient-derived xenograft tumor model were used to determine the inhibitory effects and mechanism of cirsiliol in ESCC. Results TYK2 was overexpressed and served as an oncogene in ESCC. Cirsiliol could bind with TYK2 and inhibit its activity, thereby decreasing dimer formation and nucleus localization of signal transducer and activator of transcription 3 (STAT3). Cirsiliol could inhibit ESCC growth in vitro and in vivo. Conclusions TYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-01903-z.
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Affiliation(s)
- Xuechao Jia
- Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China
| | - Chuntian Huang
- Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China
| | - Yamei Hu
- Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China
| | - Qiong Wu
- Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China
| | - Fangfang Liu
- Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China
| | - Wenna Nie
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China
| | - Hanyong Chen
- The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA
| | - Xiang Li
- Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China
| | - Zigang Dong
- Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China. .,China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. .,Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China.
| | - Kangdong Liu
- Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China. .,China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. .,Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China. .,Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, China. .,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China.
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13
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Kong L, Yang W, Chen L, Qian L. The DNA methylation-regulated MCTP1 activates the drug-resistance of esophageal cancer cells. Aging (Albany NY) 2021; 13:3342-3352. [PMID: 33571139 PMCID: PMC7906193 DOI: 10.18632/aging.104173] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 09/14/2020] [Indexed: 11/25/2022]
Abstract
Accumulating studies have demonstrated that drug-resistance remains a great obstacle for the effective treatment of cancers. Esophageal cancer is still one of the most common cancers worldwide, which also suffers from the drug-resistance during clinical treatment. Here we performed drug-resistance profiling assays and identified several drug-resistant and drug-sensitive esophageal cancer cell lines. The following methylation sequencing showed that the MCTP1 gene is hypermethylated in the drug-resistant esophageal cancer cells. As a result, the expression of MCTP1 is down-regulated in the drug-resistant esophageal cancer cells. Down-regulation of MCTP1 also affects the migration and apoptosis of esophageal cancer cells, as revealed by the wound-healing and apoptosis assays. Further investigations proposed two signaling pathways that might involve in the MCTP1-mediated drug-resistance of esophageal cancer cells. All these results suggested that MCTP1 activates the drug-resistance of esophageal cancer cells, which has implications for further design of new biomarker of esophageal cancer treatment.
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Affiliation(s)
- Lingsuo Kong
- Department of Anesthesiology, West District of The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei 230031, Anhui, P.R. China
| | - Wan Yang
- Department of Anesthesiology, West District of The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei 230031, Anhui, P.R. China
| | - Lanren Chen
- Department of Anesthesiology, West District of The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei 230031, Anhui, P.R. China
| | - Liting Qian
- Department of Radiotherapy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 3230031, Anhui, P.R. China
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14
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Yan A, Wang C, Zheng L, Zhou J, Zhang Y. MicroRNA-454-3p inhibits cell proliferation and invasion in esophageal cancer by targeting insulin-like growth factor 2 mRNA-binding protein 1. Oncol Lett 2020; 20:359. [PMID: 33133259 PMCID: PMC7590437 DOI: 10.3892/ol.2020.12223] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 07/22/2020] [Indexed: 12/12/2022] Open
Abstract
Esophageal cancer (ESCA) is the eighth most common cause of cancer-associated mortality in humans. An increasing number of studies have demonstrated that microRNAs (miRs) serve important roles in mediating tumor initiation and progression. miR-454-3p has been found to be involved in the development of various human malignancies; however, little is known about the role of miR-454-3p in esophageal cancer. In the present study, the protein and gene expression levels of miR-454-3p in ESCA tissues and cells were downregulated compared with adjacent normal tissues and normal human esophageal epithelial cells. Additionally, miR-454-3p downregulation resulted in improved survival rates in patients with ESCA, and miR-454-3p overexpression significantly suppressed cell proliferation, migration and invasion and promoted apoptosis in four ESCA cell lines (EC9706, ECA109, TE-1 and TE-8). It was found that miR-454-3p overexpression inhibited the expression of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) at the protein and mRNA expression levels. Furthermore, it was demonstrated that miR-454-3p inhibited ESCA cell proliferation, migration and apoptosis by targeting IGF2BP1 via the ERK and AKT signaling pathways in a subcutaneous xenograft tumor mouse model. These results showed that miR-454-3p functioned as an important tumor suppressor in ESCA by targeting IGFBP1. Therefore, miR-454-3p may be a novel prognostic biomarker and therapeutic target for patients with ESCA.
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Affiliation(s)
- Aiting Yan
- Department of Oncology, Affiliated Haian Hospital of Nantong University, Nantong, Jiangsu 226600, P.R. China
| | - Cuizhu Wang
- Department of Oncology, Affiliated Haian Hospital of Nantong University, Nantong, Jiangsu 226600, P.R. China
| | - Liangfeng Zheng
- Central Laboratory, Affiliated Haian Hospital of Nantong University, Nantong, Jiangsu 226600, P.R. China
| | - Jiebo Zhou
- Department of Oncology, Affiliated Haian Hospital of Nantong University, Nantong, Jiangsu 226600, P.R. China
| | - Yan Zhang
- Department of Oncology, Affiliated Haian Hospital of Nantong University, Nantong, Jiangsu 226600, P.R. China
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15
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Muhetaer A, Niyaz M, Ainiwaer J, Liwei Z, Awut E. Amplification and clinicopathological significance of HER-2 in Kazakh esophageal squamous cell carcinoma. Mol Clin Oncol 2020; 13:64. [PMID: 32968485 PMCID: PMC7500049 DOI: 10.3892/mco.2020.2134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 08/25/2020] [Indexed: 11/06/2022] Open
Abstract
Amplification and overexpression of the human epidermal growth factor receptor-2 (HER-2) gene accelerates cell division and proliferation, and promotes tumor growth and metastasis in various malignant tumors. However, there are few reports on its influence and mechanism in esophageal cancer. The aim of the present study was to investigate the gene amplification and clinicopathological significance of HER-2 in Kazakh esophageal squamous cell carcinoma (ESCC). HER-2 gene amplification was detected in 70 esophageal cancer tissues using fluorescence in situ hybridization. The association between the HER-2 gene amplification and the clinicopathological characteristics of patients with esophageal cancer was also analyzed. The amplification rate of the HER-2 gene in patients with esophageal cancer was 54.2% (38/70). The results also revealed a positive association between the amplification rate of the HER-2 gene in esophageal squamous cell carcinomas and the level of tissue differentiation, increasing gradually and significantly among the highly, moderately and poorly differentiated tissues (P<0.05). The amplification rate of the HER-2 gene in patients with lymph node metastasis was higher than those without (P<0.05). There was no significant association between the amplification rate of the HER-2 gene and any of the clinic pathological parameters, such as sex, age, depth of invasion and 3-year survival, among patients (P>0.05). In conclusion, the amplification rate of the HER-2 gene in patients with Kazakh ESCC was high. There was an association with various prognostic factors, including cancer differentiation and lymph node metastasis. HER-2 gene expression levels may be considered as an indicator of poor prognosis in patients with ESCC in the clinical setting, and this may provide a basis of treatment for individualized targeted therapies.
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Affiliation(s)
- Aishanjiang Muhetaer
- Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.,Department of Thoracic Surgery, Kashi First People's Hospital, Kashi, Xinjiang 844000, P.R. China
| | - Madiniyet Niyaz
- First Affiliated Hospital/Clinical Medicine Research Institute of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Julaiti Ainiwaer
- Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Zhang Liwei
- Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Edris Awut
- Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
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16
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管 柳, 邹 晴, 刘 倩, 陈 斯. [Comparison of B-NDG ? and BALB/c mouse models bearing patient-derived xenografts of esophageal squamous cell carcinoma]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2020; 40:1200-1206. [PMID: 32895183 PMCID: PMC7429172 DOI: 10.12122/j.issn.1673-4254.2020.08.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Indexed: 12/08/2022]
Abstract
OBJECTIVE To investigate the difference of tumor formation in different mouse strains bearing patient-derived xenograft of esophageal squamous cell carcinoma(ESCC) and establish a better animal model for preclinical study of individualized treatment of ESCC. METHODS The tumor tissues collected from 22 ESCC patients were used to establish tumor-bearing mouse models in B-NDG? (NSG) mice and BALB/c nude mice. The tumor formation rate and tumor formation time were compared between the two mouse models, and HE staining, immunohistochemistry and genome sequencing were carried out to assess the consistency between transplanted tumor tissues in the models and patient-derived tumor tissues. RESULTS The tumor-bearing models were established successfully in both NSG mice (50%, 11/22) and BALB/c nude mice (18.18%, 4/22). The average tumor formation time was significantly shorter in NSG mice than in BALB/c nude mice (75.95 vs 91.67 days, P < 0.001). In both of the mouse models, the transplanted tumors maintained morphological characteristics identical to those of patient-derived ESCC tumors. Genetic analysis showed that the xenografts in NSG mice had a greater genetic similarity to the patients' tumors than those in BALB/c nude mice (P < 0.0001). CONCLUSIONS Mouse models bearing xenografts of patient-derived ESCC can be successfully established in both NSG mice and BALB/c nude mice, but the models in the former mouse strain can be more reliable.
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Affiliation(s)
- 柳柳 管
- 广东药科大学附属第一医院肿瘤科，广东 广州 510080Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
- 广东省食管癌精准治疗工程技术研究中心，广东 广州 510080Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, Guangzhou 510080, China
| | - 晴晴 邹
- 广东药科大学附属第一医院肿瘤科，广东 广州 510080Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
- 广东省食管癌精准治疗工程技术研究中心，广东 广州 510080Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, Guangzhou 510080, China
| | - 倩 刘
- 广东省食管癌精准治疗工程技术研究中心，广东 广州 510080Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, Guangzhou 510080, China
- 广东药科大学附属第一医院科学研究中心，广东 广州 510080Scientific Research Center, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
| | - 斯泽 陈
- 广东药科大学附属第一医院肿瘤科，广东 广州 510080Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
- 广东省食管癌精准治疗工程技术研究中心，广东 广州 510080Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, Guangzhou 510080, China
- 广东药科大学附属第一医院科学研究中心，广东 广州 510080Scientific Research Center, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
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17
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Patel AK, Pan X, Vila DM, Frankel WL, Chen W, Perry KA, Merritt RE, D'Souza DM, Wuthrick EJ, Williams TM. Perineural invasion predicts for locoregional failure in patients with oesophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy. J Clin Pathol 2020; 74:228-233. [PMID: 32317290 DOI: 10.1136/jclinpath-2020-206424] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/06/2020] [Accepted: 03/21/2020] [Indexed: 11/04/2022]
Abstract
AIM The prognostic significance of perineural invasion (PNI) in oesophageal adenocarcinoma (EAC) is unclear. We examined the association of PNI with clinical outcomes in patients treated with neoadjuvant chemoradiotherapy (nCRT) and surgery. METHODS We performed a single institutional retrospective study. We evaluated the association of PNI with locoregional recurrence-free survival (LRFS), distant metastasis-free survival, disease-free survival (DFS) and overall survival using log-rank and Cox proportional hazard modelling. RESULTS 29 out of 73 patients (40%) had PNI at the time of surgery. The median follow-up was 20.1 months. The median DFS was 18.4 months for patients with PNI vs 41.3 months for patients without PNI (p<0.05). The median LRFS was 23.3 months for patients with PNI and median not reached for patients without PNI (p<0.01). In a multivariate model including age and pathological variables, PNI remained a significant independent predictor of LRFS (HR 0.20, 95% CI 0.07 to 0.60; p=0.004). CONCLUSIONS For patients with EAC treated with nCRT, PNI found at the time of surgery is significantly associated with worse LRFS. Our data support attempts to validate this finding and perhaps testing the role of adjuvant therapy in patients with PNI.
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Affiliation(s)
- Ankur K Patel
- Department of Radiation Oncology, Ohio State University James Cancer Hospital, Columbus, Ohio, USA
| | - Xueliang Pan
- Department of Biomedical Informatics, Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Diana M Vila
- Department of Radiation Oncology, Ohio State University James Cancer Hospital, Columbus, Ohio, USA
| | - Wendy L Frankel
- Department of Pathology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Wei Chen
- Department of Pathology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Kyle A Perry
- Division of General and Gastrointestinal Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Robert E Merritt
- Division of Thoracic Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Desmond M D'Souza
- Division of Thoracic Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Evan J Wuthrick
- Department of Radiation Oncology, Ohio State University James Cancer Hospital, Columbus, Ohio, USA
| | - Terence M Williams
- Department of Radiation Oncology, Ohio State University James Cancer Hospital, Columbus, Ohio, USA
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Chu LY, Peng YH, Weng XF, Xie JJ, Xu YW. Blood-based biomarkers for early detection of esophageal squamous cell carcinoma. World J Gastroenterol 2020; 26:1708-1725. [PMID: 32351288 PMCID: PMC7183865 DOI: 10.3748/wjg.v26.i15.1708] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 03/13/2020] [Accepted: 03/19/2020] [Indexed: 02/06/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system worldwide, especially in China. Due to the lack of effective early detection methods, ESCC patients often present at an advanced stage at the time of diagnosis, which seriously affects the prognosis of patients. At present, early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy. Therefore, there is an unmet need for a non-invasive method to detect ESCC in the early stages. With the emergence of a large class of non-invasive diagnostic tools, serum tumor markers have attracted much attention because of their potential for detection of early tumors. Therefore, the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC. This article reviews the recent advances in the discovery of blood-based ESCC biomarkers, and discusses the origins, clinical applications, and technical challenges of clinical validation of various types of biomarkers.
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Affiliation(s)
- Ling-Yu Chu
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Xue-Fen Weng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jian-Jun Xie
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
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Feng AL, Han X, Meng X, Chen Z, Li Q, Shu W, Dai H, Zhu J, Yang Z. PRDX2 plays an oncogenic role in esophageal squamous cell carcinoma via Wnt/β-catenin and AKT pathways. Clin Transl Oncol 2020; 22:1838-1848. [PMID: 32130676 DOI: 10.1007/s12094-020-02323-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Accepted: 02/12/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE To investigate the role of PRDX2 in esophageal carcinoma (ESCA). METHODS The expression of PRDX2 was detected in ESCA tissues. And PRDX2 expression in two ESCA cell lines was knocked down. Cell proliferation, metastasis and invasion were detected in these cells. RESULTS Here, we found that PRDX2 expression was significantly increased in ESCA tissues and was associated with a poor prognosis in ESCA patients. In addition, PRDX2 expression was significantly associated with pathological grading, infiltration degree and 5-year survival time in ESCA patients. Next, we knocked down PRDX2 expression by PRDX2-shRNA transfection in two ESCA cell lines, Eca-109 and TE-1. Proliferation analysis indicated that in vitro PRDX2 knockdown decreased growth and clone formation of ESCA cells. Scratch and transwell assays indicated that cell migration and invasion were significantly inhibited by PRDX2 knockdown. In addition, PRDX2 knockdown inhibited cell cycle of ESCA cells and down-regulated Cyclin D1-CDK4/6. Moreover, PRDX2 knockdown regulated proteins involved in mitochondrial-dependent apoptosis, including increased Bax and Caspase9/3 and decreased Bcl2. Mechanism investigation indicated that PRDX2 knockdown led to inactivation of Wnt/β-catenin and AKT pathways. CONCLUSIONS Our data suggest that PRDX2 may function as an oncogene in the development of ESCA via regulating Wnt/β-catenin and AKT pathways. Our study fills a gap in the understanding of the role of PRDX2 in ESCA and provides a potential target for ESCA treatment.
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Affiliation(s)
- A L Feng
- Department of Oncology, Shandong Provincial Hospital Affiliated To Shandong University, 324# Jing 5 Road, Jinan, 250021, People's Republic of China
| | - X Han
- Experimental Department, Affiliated Tumor Hospital of Guangxi Medical University, 71# Hedi Road, Nanning, 530021, People's Republic of China
| | - X Meng
- Department of Oncology, Shandong Provincial Hospital Affiliated To Shandong University, 324# Jing 5 Road, Jinan, 250021, People's Republic of China
| | - Z Chen
- Department of Oncology, Shandong Provincial Hospital Affiliated To Shandong University, 324# Jing 5 Road, Jinan, 250021, People's Republic of China
| | - Q Li
- Department of Oncology, Shandong Provincial Hospital Affiliated To Shandong University, 324# Jing 5 Road, Jinan, 250021, People's Republic of China
| | - W Shu
- Department of Oncology, Shandong Provincial Hospital Affiliated To Shandong University, 324# Jing 5 Road, Jinan, 250021, People's Republic of China
| | - H Dai
- Department of Oncology, Shandong Provincial Hospital Affiliated To Shandong University, 324# Jing 5 Road, Jinan, 250021, People's Republic of China
| | - J Zhu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, 16766# Jingshi Road, Jinan, 250014, People's Republic of China.
| | - Z Yang
- Department of Oncology, Shandong Provincial Hospital Affiliated To Shandong University, 324# Jing 5 Road, Jinan, 250021, People's Republic of China.
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20
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Sun H, Wang L, Zhao Q, Dai J. Diagnostic and prognostic value of serum miRNA-1290 in human esophageal squamous cell carcinoma. Cancer Biomark 2020; 25:381-387. [PMID: 31306104 DOI: 10.3233/cbm-190007] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND It is well known that some circulating microRNAs (miRNAs) are highly stable and might serve as promising biomarkers for many types of human cancer including esophageal squamous cell carcinoma (ESCC). However, the potential clinical significance of serum miR-1290 in ESCC remained unknown. OBJECTIVE The aim of this study was to investigate the diagnostic and prognostic value of serum miR-1290 for ESCC. METHODS The expression levels of serum miRNA-1290 in patients with ESCC and healthy controls were detected, and their potential diagnostic and prognostic value was analyzed. RESULTS Our results showed that tissue and serum miR-1290 levels were both significantly elevated in ESCC compared to their respective controls. Tissue miR-1290 levels were highly correlated with serum miR-1290 levels. High serum miR-1290 levels were significantly associated with worse clinicopathological characteristics. Patients with high serum miR-1290 levels had significantly worse survival. Further multivariate analysis showed that serum miR-1290 was an independent risk factor for ESCC. Serum miR-1290 could effectively discriminate ESCC cases from normal controls. CONCLUSIONS The level of serum microRNA-1290 in ESCC patients increased significantly, and its expression level could reflect the progress of ESCC, suggesting that serum microRNA-1290 might be a useful diagnostic and prognostic marker of ESCC.
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Affiliation(s)
- Haijun Sun
- Nanjing Medical University Affiliated Lianyungang Clinical College, Department of Thoracic Surgery, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China.,Nanjing Medical University Affiliated Lianyungang Clinical College, Department of Thoracic Surgery, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China
| | - Lei Wang
- Nanjing Medical University Affiliated Lianyungang Clinical College, Department of Oncology, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China.,Nanjing Medical University Affiliated Lianyungang Clinical College, Department of Thoracic Surgery, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China
| | - Qingqing Zhao
- Nanjing Medical University Affiliated Lianyungang Clinical College, Department of Thoracic Surgery, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China.,Nanjing Medical University Affiliated Lianyungang Clinical College, Department of Thoracic Surgery, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China
| | - Jianhua Dai
- Nanjing Medical University Affiliated Lianyungang Clinical College, Department of Thoracic Surgery, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China
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21
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Fanelli GN, Loupakis F, Smyth E, Scarpa M, Lonardi S, Pucciarelli S, Munari G, Rugge M, Valeri N, Fassan M. Pathological Tumor Regression Grade Classifications in Gastrointestinal Cancers: Role on Patients' Prognosis. Int J Surg Pathol 2019; 27:816-835. [PMID: 31416371 DOI: 10.1177/1066896919869477] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Preoperative chemotherapy or combined radiotherapy and chemotherapy (CRT), followed by surgery, represents the standard approach for locally advanced esophageal, gastric, and rectal carcinomas. To adequately evaluate the effects of neoadjuvant CRT in the resection specimens, several histopathologic tumor regression grade (TRG) scoring systems have been introduced into clinical practice. The primary goal of these TRG systems relies on a correct prognostic stratification of patients in the attempt to help clinical decision-making and influence surgical strategies, postoperative adjuvant therapies, and surveillance intensity. However, most TRG systems suffer from poor reproducibility and low interobserver concordance rates. Many efforts have been made in the identification of alternative, robust, simple, and universally accepted TRG scoring systems, which would help in the comparison of different treatment strategies and in the standardization of multimodal therapies. The aim of this review is to analyze the most commonly used TRG systems in gastrointestinal cancers highlighting their pitfalls and usefulness, depending on the tumor type.
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Affiliation(s)
| | | | | | - Marco Scarpa
- Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | - Sara Lonardi
- Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | | | | | | | - Nicola Valeri
- Royal Marsden Hospital, London and Sutton, UK
- The Institute of Cancer Research, London and Sutton, UK
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22
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Lian SH, Song JD, Huang Y. PBF, a Proto-oncogene in Esophageal Carcinoma. Open Med (Wars) 2019; 14:748-756. [PMID: 31637306 PMCID: PMC6795029 DOI: 10.1515/med-2019-0086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 07/26/2019] [Indexed: 11/15/2022] Open
Abstract
Emerging evidence shows that the pituitary tumour-transforming gene (PTTG)-binding factor (PBF) functions as a proto-oncogene in some tumors. However, the precise functions of PBF in tumorigenesis and its action mechanisms remain largely unknown. Here for the first time we demonstrated that PBF was associated with a tumor-related cell phenotype in esophageal carcinoma (ESCA) and identified the involved signaling pathways. PBF was up-regulated in ESCA tissues (Data from GEPIA) and cells. Then we down-regulated PBF in ESCA cell lines, Eca-109 and TE-1, by using RNAi technology. Cell function analysis suggested that down-regulation of PBF could inhibit tumor-related cell phenotypes, including proliferation, motility, apoptosis and cell cycle, in Eca-109 and TE-1 cells. Mechanism investigation suggested that apoptosis induced by PBF knockdown may be mediated by the activation of the mitochondrial apoptosis pathway and cell cycle arrest. AKT/mTOR and Wnt3a/β-catenin, key pathways in regulating tumor proliferation and metastasis, were found to be inactivated by the down-regulation of PBF in ESCA cells. In conclusion, our study demonstrates that PBF functions as a proto-oncogene in ESCA in vitro, which may be mediated through AKT/mTOR and Wnt3a/β-catenin pathways.
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Affiliation(s)
- Shi-hai Lian
- Department of Cardiothoracic surgery, Zaozhuang Municipal Hospital, Zaozhuang 277000, Shandong Province, China
| | - Jun-ding Song
- Department of Cardiothoracic surgery, Zaozhuang Municipal Hospital, Zaozhuang 277000, Shandong Province, China
| | - Yi Huang
- Department of Cardiothoracic surgery, Zaozhuang Municipal Hospital, 41# Longtou Rd, Zaozhuang 277100, Shandong Province, China
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23
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Long noncoding RNA PANDA promotes esophageal squamous carcinoma cell progress by dissociating from NF-YA but interact with SAFA. Pathol Res Pract 2019; 215:152604. [DOI: 10.1016/j.prp.2019.152604] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 08/03/2019] [Accepted: 08/16/2019] [Indexed: 12/15/2022]
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Xu YW, Peng YH, Xu LY, Xie JJ, Li EM. Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma. World J Gastroenterol 2019; 25:5049-5068. [PMID: 31558856 PMCID: PMC6747294 DOI: 10.3748/wjg.v25.i34.5049] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 07/28/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EGJA) are the two main types of gastrointestinal cancers that pose a huge threat to human health. ESCC remains one of the most common malignant diseases around the world. In contrast to the decreasing prevalence of ESCC, the incidence of EGJA is rising rapidly. Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers. Current approaches for early diagnosis mainly depend on invasive and costly endoscopy. Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients. Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis, making them promising biomarkers for early detection and monitoring of ESCC and EGJA. In this review, we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.
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Affiliation(s)
- Yi-Wei Xu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Li-Yan Xu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jian-Jun Xie
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - En-Min Li
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
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Xu J, Lv H, Zhang B, Xu F, Zhu H, Chen B, Zhu C, Shen J. miR-30b-5p acts as a tumor suppressor microRNA in esophageal squamous cell carcinoma. J Thorac Dis 2019; 11:3015-3029. [PMID: 31463131 DOI: 10.21037/jtd.2019.07.50] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background To study miR-30b-5p expression in esophageal squamous cell carcinoma (ESCC) by comparisons between tumor tissues and matched adjacent non-cancerous tissues to elucidate the correlation between miR-30b-5p expression and ESCC clinical parameters, and to explore the signaling pathways associated with miR-30b-5p and key target genes. Methods Clinical data, cancer tissues, and adjacent non-cancerous tissues of 32 patients diagnosed with ESCC were collected from Taizhou Hospital of Zhejiang Province. The expression levels of miR-30b-5p were determined by real-time polymerase chain reaction (RT-PCR). mRNA data for ESCC tissues and normal tissues, and clinical materials of patients with ESCC were obtained from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Associations between miR-30b-5p expression and clinical features of patients with ESCC and overall survival were explored. A bioinformatics analysis was performed to determine the pathways and key miR-30b-5p targets associated with ESCC. Additionally, a cytological experiment was performed to evaluate the biological functions of miR-30b-5p. Finally, correlations between miR-30b-5p and key targets involved in PI3K/Akt signaling pathways were validated by western blotting. Results The expression level of miR-30b-5p in the 32 ESCC tissues was significantly lower than that in adjacent normal tissues (P<0.01) and was significantly disparate in the T stage, with higher expression in T1 than in T2 (P<0.05). Among the patients with higher expression levels of miR-30b-5p in ESCC tissues than in adjacent normal tissues, patients with higher expression of miR-30b-5p had a better prognosis (P<0.05). An analysis of gene chip data from the GEO database showed similar results. A gene enrichment analysis indicated a series of pathways that may be associated with the downregulation of miR-30b-5p, including focal adhesion, ECM-receptor interaction, and PI3K/Akt signaling pathways. Seven key target genes (PDGFRB, VIM, ITGA5, ACTN1, THBS2, SERPINE1, and RUNX2) were identified; these were found to be upregulated in ESCC tissues and were negatively correlated with miR-30b-5p. Functional experiments showed that miR-30b-5p attenuated migration (P<0.01) and invasion (P<0.05) in the Eca109 cell line. Moreover, the levels of ITGA5, PDGFRB, p-PI3K, and p-AKT, which are involved in the PI3K/Akt signaling pathway, were decreased in the miR-30b-5p-overexpressing Eca109 cell line. Conclusions Upregulated miR-30b-5p may inhibit migration and invasion in ESCC by targeting ITGA5, PDGFRB, and signaling pathways, such as PI3K/Akt, involved in ESCC regulation. Our results indicate that miR-30b-5p plays an important role in the occurrence and progression of ESCC and is a potential therapeutic target.
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Affiliation(s)
- Jianfeng Xu
- Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou 317000, China
| | - Haiyan Lv
- Enze Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou 317000, China
| | - Bo Zhang
- Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou 317000, China
| | - Feng Xu
- Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou 317000, China
| | - Hongyu Zhu
- Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou 317000, China
| | - Baofu Chen
- Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou 317000, China
| | - Chengchu Zhu
- Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou 317000, China
| | - Jianfei Shen
- Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou 317000, China
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A Novel Neighborhood-Based Computational Model for Potential MiRNA-Disease Association Prediction. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2019; 2019:5145646. [PMID: 30800172 PMCID: PMC6360053 DOI: 10.1155/2019/5145646] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Accepted: 12/11/2018] [Indexed: 01/08/2023]
Abstract
In recent years, more and more studies have shown that miRNAs can affect a variety of biological processes. It is important for disease prevention, treatment, diagnosis, and prognosis to study the relationships between human diseases and miRNAs. However, traditional experimental methods are time-consuming and labour-intensive. Hence, in this paper, a novel neighborhood-based computational model called NBMDA is proposed for predicting potential miRNA-disease associations. Due to the fact that known miRNA-disease associations are very rare and many diseases (or miRNAs) are associated with only one or a few miRNAs (or diseases), in NBMDA, the K-nearest neighbor (KNN) method is utilized as a recommendation algorithm based on known miRNA-disease associations, miRNA functional similarity, disease semantic similarity, and Gaussian interaction profile kernel similarity for miRNAs and diseases to improve its prediction accuracy. And simulation results demonstrate that NBMDA can effectively infer miRNA-disease associations with higher accuracy compared with previous state-of-the-art methods. Moreover, independent case studies of esophageal neoplasms, breast neoplasms and colon neoplasms are further implemented, and as a result, there are 47, 48, and 48 out of the top 50 predicted miRNAs having been successfully confirmed by the previously published literatures, which also indicates that NBMDA can be utilized as a powerful tool to study the relationships between miRNAs and diseases.
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Chetwood JD, Garg P, Finch P, Gordon M. Systematic review: the etiology of esophageal squamous cell carcinoma in low-income settings. Expert Rev Gastroenterol Hepatol 2019; 13:71-88. [PMID: 30791842 DOI: 10.1080/17474124.2019.1543024] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Esophageal carcinoma causes over 380 000 deaths per year, ranking sixth worldwide in mortality amongst all malignancies. Globally, the squamous cell subtype is most common and accounts for 80% of esophageal cancers. Nonetheless, esophageal squamous cell carcinoma is much more poorly understood than esophageal adenocarcinoma, including what is driving such high prevalences, why it often presents in young patients, and shows such marked geographical delineations Areas covered: The current literature was searched for articles focusing on aetiopathogenesis of squamous cell esophageal carcinoma via a systematic review, particularly in low-resource settings. This was supplemented by papers of interest known to the authors. Expert commentary: Current putative mechanisms include polycyclic aromatic hydrocarbons, nitrosamines, acetaldehyde, cyclo-oxygenase-2 pathways, androgen and their receptor levels, as well as smoking & alcohol, micronutrient deficiencies and diet, mycotoxins, thermal damage, oral hygiene and microbiotal factors, inhaled smoke, viral infections such as HPV, and chronic irritative states. Etiology is likely multifactorial and varies geographically. Though smoking and alcohol play a predominant role in high-income settings, there is strong evidence that mycotoxins, diet and temperature effects may play an under-recognized role in low and middle-income settings.
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Affiliation(s)
- John David Chetwood
- a Malawi Liverpool Wellcome Trust Clinical Research Programme , Blantyre , Malawi
| | - Priya Garg
- a Malawi Liverpool Wellcome Trust Clinical Research Programme , Blantyre , Malawi
| | | | - Melita Gordon
- a Malawi Liverpool Wellcome Trust Clinical Research Programme , Blantyre , Malawi.,b College of Medicine , Blantyre , Malawi.,c Institute of Infection and Global Health , University of Liverpool , Liverpool , UK
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Zhang J, Fa X, Zhang Q. MicroRNA‑206 exerts anti‑oncogenic functions in esophageal squamous cell carcinoma by suppressing the c‑Met/AKT/mTOR pathway. Mol Med Rep 2018; 19:1491-1500. [PMID: 30569129 PMCID: PMC6390054 DOI: 10.3892/mmr.2018.9775] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 10/12/2018] [Indexed: 12/27/2022] Open
Abstract
Increasing evidence suggests that the dysregulation of microRNAs (miRNAs) has an important role in the progression of human cancer, including ESCC. However, the exact functions and mechanisms of miRNAs in ESCC remain largely unclear. The aim of the present study was to investigate the expression and biological functions of miRNAs in ESCC and reveal the underlying molecular mechanisms. miRNA microarray and reverse transcription-quantitative polymerase chain reaction analyses were performed, which identified and confirmed that miR-206 was significantly downregulated in ESCC tissues and cell lines. Its low expression was associated with lymph node metastasis, advanced TNM stage and N classification, as well as poorer overall survival in patients with ESCC. CCK-8 and flow cytometry assays demonstrated that ectopic miR-206 expression inhibited ESCC cell proliferation and induced cell apoptosis. In addition, MET proto-oncogene, receptor tyrosine kinase (c-Met), a well-known oncogene, was a direct target of miR-206. An inverse correlation between the levels of miR-206 and c-Met mRNA in ESCC tissue samples was confirmed. Notably, c-Met overexpression inhibited the effects of miR-206 on the proliferation and apoptosis of ESCC cells. Additionally, it was confirmed that the tumor-suppressive functions of miR-206 may have contributed to the inactivation of the c-Met/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. In conclusion, the findings of the present study suggested that miR-206 exerts its anti-cancer functions via the c-Met/AKT/mTOR signaling pathway, providing a novel candidate prognostic factor and a potential therapeutic target in ESCC.
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Affiliation(s)
- Jin Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Xianen Fa
- Department of Cardiac Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Qingyong Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
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[ 99mTc]3PRGD 2 for integrin receptor imaging of esophageal cancer: a comparative study with [ 18F]FDG PET/CT. Ann Nucl Med 2018; 33:135-143. [PMID: 30392070 DOI: 10.1007/s12149-018-1315-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Accepted: 10/29/2018] [Indexed: 10/27/2022]
Abstract
OBJECTIVES This study was designed to investigate the efficacy of 99mtechnetium-three polyethylene glycol spacers-arginine-glycine-aspartic acid ([99mTc]3PRGD2) in the evaluation of patients with esophageal cancer. METHODS Twenty-nine patients with a suspected esophageal lesion and for whom definite pathological diagnosis was finally obtained were recruited. Whole-body planar scanning and chest single-photon-emission computed tomography/computed tomography (SPECT/CT) were performed at 30 and 40 min, respectively, after intravenous injection of 11.1 MBq/kg of [99mTc]3PRGD2. 2-Deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) positron-emission tomography/computed tomography (PET/CT) was performed in 1 week. The tumor-to-background ratio (T/B) and the maximum standard uptake value (SUVmax) were calculated for semi-quantitative and quantitative analyses. Integrin αvβ3 was analyzed through immunohistochemistry. RESULTS The T/B, SUVmax and expression of integrin αvβ3 in malignant lesions were higher than those in benign lesions (t = 3.691, P = 0.001; t = 8.271, P = 0.000; t = 3.632, P = 0.001, respectively). There was a significant correlation between T/B and SUVmax in esophageal lesions (r = 0.660, P = 0.000). The expression of integrin αvβ3 was correlated with [99mTc]3PRGD2 uptake (r = 0.782, P = 0.000). In visual analysis, the sensitivity and accuracy of the whole-body planar RGD scan were lower than those of the chest SPECT/CT RGD scan and the [18F]FDG PET/CT scan (x2 = 6.769, P = 0.022). The sensitivity, specificity and accuracy of the chest SPECT/CT RGD scan were similar to those of the [18F] FDG PET/CT scan. In semi-quantitative analysis, the sensitivity, specificity and accuracy of chest SPECT/CT RGD from the receiver operating characteristic (ROC) analysis were 87%, 100% and 94%, respectively [cutoff = 3.1 of T/B, area under the curve (AUC) = 0.957]. Thirteen patients (30 lymph nodes) and 16 patients (105 lymph nodes) were suspected to have lymph node metastases based on the RGD and FDG scans, respectively. CONCLUSION This prospective study demonstrated that [99mTc]3PRGD2 imaging is valuable for the diagnosis and staging of esophageal cancer. It may be less sensitive than [18F]FDG imaging for detecting metastatic lesions in small lymph nodes. The T/B value was correlated with the expression of integrin αvβ3. NIH CLINICALTRIALS.GOV: NCT 02744729.
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Xie X, Liu K, Liu F, Chen H, Wang X, Zu X, Ma X, Wang T, Wu Q, Zheng Y, Bode AM, Dong Z, Kim DJ. Gossypetin is a novel MKK3 and MKK6 inhibitor that suppresses esophageal cancer growth in vitro and in vivo. Cancer Lett 2018; 442:126-136. [PMID: 30391783 DOI: 10.1016/j.canlet.2018.10.016] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 10/11/2018] [Accepted: 10/22/2018] [Indexed: 01/04/2023]
Abstract
Gossypetin as a hexahydroxylated flavonoid found in many flowers and Hibiscus. It exerts various pharmacological activities, including antioxidant, antibacterial and anticancer activities. However, the anticancer capacity of gossypetin has not been fully elucidated. In this study, gossypetin was found to inhibit anchorage-dependent and -independent growth of esophageal cancer cells. To identify the molecular target(s) of gossypetin, various signaling protein kinases were screened and results indicate that gossypetin strongly attenuates the MKK3/6-p38 signaling pathway by directly inhibiting MKK3 and MKK6 protein kinase activity in vitro. Mechanistic investigations showed that arginine-61 in MKK6 is critical for binding with gossypetin. Additionally, the inhibition of cell growth by gossypetin is dependent on the expression of MKK3 and MKK6. Gossypetin caused G2 phase cell cycle arrest and induced intrinsic apoptosis by activating caspases 3 and 7 and increasing the expression of BAX and cytochrome c. Notably, gossypetin suppressed patient-derived esophageal xenograft tumor growth in an in vivo mouse model. Our findings suggest that gossypetin is an MKK3 and MKK6 inhibitor that could be useful for preventing or treating esophageal cancer.
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Affiliation(s)
- Xiaomeng Xie
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China
| | - Kangdong Liu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China; The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450008, China; The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, Henan, 450008, China; The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450008, China
| | - Feifei Liu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China
| | - Hanyong Chen
- The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA
| | - Xiangyu Wang
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China
| | - Xueyin Zu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China; The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450008, China
| | - Xiaoli Ma
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China; The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450008, China
| | - Ting Wang
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China; The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450008, China
| | - Qiong Wu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China; The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450008, China
| | - Yan Zheng
- The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, Henan, 450008, China
| | - Ann M Bode
- The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA
| | - Zigang Dong
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China; The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450008, China; The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
| | - Dong Joon Kim
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China.
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Huang D, Wang Y, He Y, Wang G, Wang W, Han X, Sun Y, Lin L, Shan B, Shen G, Cheng M, Bian G, Fang X, Hu S, Pan Y. Paraoxonase 3 is involved in the multi-drug resistance of esophageal cancer. Cancer Cell Int 2018; 18:168. [PMID: 30386177 PMCID: PMC6198441 DOI: 10.1186/s12935-018-0657-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 10/08/2018] [Indexed: 02/06/2023] Open
Abstract
Background Drug resistance prevents the effective treatment of cancers. DNA methylation has been found to participate in the development of cancer drug resistance. Methods We performed the wound-healing and invasion assays to test the effect of the paraoxonase gene PON3 on esophageal cancer (EC) cells. In addition, in vivo EC-derived tumor xenografts in nude mice were generated to test the effect of PON3 on the chemoresistance of EC cells. Results We found that PON3 is hypermethylated in drug-resistant EC cell line K150, which in-return down-regulates its expression. The following experiments by the forced changes of PON3 level in vitro and in vivo demonstrated that the PON3 expression negatively correlates with drug resistance in EC cells. Further wound-healing and invasion assays showed that PON3 suppresses the migration and invasion of EC cells. Conclusion Our data established that PON3 is associated with the EC drug resistance, which may serve as a biomarker for the potential therapeutic treatment of EC. Electronic supplementary material The online version of this article (10.1186/s12935-018-0657-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Dabing Huang
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China.,3Department of Geriatrics, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, 230001 Anhui People's Republic of China.,Gerontology Institute of Anhui Province, Hefei, 230001 Anhui People's Republic of China
| | - Yong Wang
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China
| | - Yifu He
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China
| | - Gang Wang
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China
| | - Wei Wang
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China
| | - Xinghua Han
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China
| | - Yubei Sun
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China
| | - Lin Lin
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China
| | - Benjie Shan
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China
| | - Guodong Shen
- 2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China.,3Department of Geriatrics, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, 230001 Anhui People's Republic of China.,Gerontology Institute of Anhui Province, Hefei, 230001 Anhui People's Republic of China
| | - Min Cheng
- 2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China.,3Department of Geriatrics, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, 230001 Anhui People's Republic of China.,Gerontology Institute of Anhui Province, Hefei, 230001 Anhui People's Republic of China
| | - Geng Bian
- 2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China.,3Department of Geriatrics, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, 230001 Anhui People's Republic of China.,Gerontology Institute of Anhui Province, Hefei, 230001 Anhui People's Republic of China
| | - Xiang Fang
- 2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China.,3Department of Geriatrics, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, 230001 Anhui People's Republic of China.,Gerontology Institute of Anhui Province, Hefei, 230001 Anhui People's Republic of China
| | - Shilian Hu
- 2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China.,3Department of Geriatrics, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, 230001 Anhui People's Republic of China.,Gerontology Institute of Anhui Province, Hefei, 230001 Anhui People's Republic of China
| | - Yueyin Pan
- 1Department of Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.,2Department of Oncology, The Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui People's Republic of China
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Niu YW, Liu H, Wang GH, Yan GY. Maximal entropy random walk on heterogenous network for MIRNA-disease Association prediction. Math Biosci 2018; 306:1-9. [PMID: 30336146 DOI: 10.1016/j.mbs.2018.10.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 10/08/2018] [Accepted: 10/13/2018] [Indexed: 12/24/2022]
Abstract
The last few decades have verified the vital roles of microRNAs in the development of human diseases and witnessed the increasing interest in the prediction of potential disease-miRNA associations. Owning to the open access of many miRNA-related databases, up until recently, kinds of feasible in silico models have been proposed. In this work, we developed a computational model of Maximal Entropy Random Walk on heterogenous network for MiRNA-disease Association prediction (MERWMDA). MERWMDA integrated known disease-miRNA association, pair-wise functional relation of miRNAs and pair-wise semantic relation of diseases into a heterogenous network comprised of disease and miRNA nodes full of information. As a kind of widely-applied biased walk process with more randomness, MERW was then implemented on the heterogenous network to reveal potential disease-miRNA associations. Cross validation was further performed to evaluate the performance of MERWMDA. As a result, MERWMDA obtained AUCs of 0.8966 and 0.8491 respectively in the aspect of global and local leave-one-out cross validation. What' more, three different case study strategies on four human complex diseases were conducted to comprehensively assess the quality of the model. Specifically, one kind of case study on Esophageal cancer and Prostate cancer were conducted based on HMDD v2.0 database. 94% and 88% out of the top 50 ranked miRNAs were confirmed by recent literature, respectively. To simulate new disease without known related miRNAs, Lung cancer (confirmed ratio 94%) associated miRNAs were removed for case study. Lymphoma (verified ratio 88%) was adopted to assess the prediction robustness of MERWMDA based on HMDD v1.0 database. We anticipated that MERWMDA could offer valuable candidates for in vitro biomedical experiments in future.
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Affiliation(s)
- Ya-Wei Niu
- School of Mathematics, Shandong University, Jinan 250100, China
| | - Hua Liu
- School of Mathematics, Shandong University, Jinan 250100, China
| | - Guang-Hui Wang
- School of Mathematics, Shandong University, Jinan 250100, China.
| | - Gui-Ying Yan
- Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China
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Zhao Y, Chen X, Yin J. A Novel Computational Method for the Identification of Potential miRNA-Disease Association Based on Symmetric Non-negative Matrix Factorization and Kronecker Regularized Least Square. Front Genet 2018; 9:324. [PMID: 30186308 PMCID: PMC6111239 DOI: 10.3389/fgene.2018.00324] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 07/30/2018] [Indexed: 12/31/2022] Open
Abstract
Increasing evidence has indicated that microRNAs (miRNAs) are associated with numerous human diseases. Studying the associations between miRNAs and diseases contributes to the exploration of effective diagnostic and treatment approaches for diseases. Unfortunately, the use of biological experiments to reveal the potential associations between miRNAs and diseases is time consuming and costly. Therefore, it is very necessary to use simple and efficient calculation models to predict potential disease-related miRNAs. Considering the limitations of other previous methods, we proposed a novel computational model of Symmetric Nonnegative Matrix Factorization for MiRNA-Disease Association prediction (SNMFMDA) to reveal the relation of miRNA-disease pairs. SNMFMDA could be applied to predict miRNAs associated with new diseases. Compared to the direct use of the integrated similarity in previous computational models, the integrated similarity need to be interpolated by symmetric non-negative matrix factorization (SymNMF) before application in SNMFMDA, and the relevant probability of disease-miRNA was obtained mainly through Kronecker regularized least square (KronRLS) method in our model. What's more, the AUC of global leave-one-out cross validation (LOOCV) reached 0.9007, and the AUC based on local LOOCV was 0.8426. Besides, the mean and the standard deviation of AUCs achieved 0.8830 and 0.0017 respectively in 5-fold cross validation. All of the above results demonstrated the superior prediction performance of SNMFMDA. We also conducted three different case studies on Esophageal Neoplasms, Breast Neoplasms and Lung Neoplasms, and 49, 49, and 48 of the top 50 of their predicted miRNAs respectively were confirmed by databases or related literatures. It could be expected that SNMFMDA would be a model with the ability to predict disease-related miRNAs efficiently and accurately.
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Affiliation(s)
- Yan Zhao
- School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, China
| | - Xing Chen
- School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, China
| | - Jun Yin
- School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, China
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Zhang Y, Jin X, Wang Z, Zhang X, Liu S, Liu G. Downregulation of SNHG1 suppresses cell proliferation and invasion by regulating Notch signaling pathway in esophageal squamous cell cancer. Cancer Biomark 2018; 21:89-96. [PMID: 29081407 DOI: 10.3233/cbm-170286] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) exert important functions involved in tumorigenesis and cancer progression including esophageal squamous cell cancer (ESCC), however, the clinical role and underlying biological function of Small Nucleolar RNA Host Gene 1 (SNHG1) in ESCC is not well known. METHODS Quantitative Real-time polymerase chain reaction (QRT-PCR) was used to detect the SNHG1 expression levels in ESCC tissues and adjacent non-cancerous tissues. Chi-square test was used to evaluate the association between clinicopathological features and SNHG1 expression in ESCC patients, Kaplan-Meier curve and log rank test was performed to analyze the association between overall survival and SNHG1 expression. Cell proliferation and invasion was assessed by MTT assay, colony formation, and transwell cell invasion assays. Western blot were also performed to examine protein expression levels of E-cadherin, Vimentin and N-cadherin, Notch 1 and Hes-1. RESULTS We demonstrated that lncRNA SNHG1 was significantly up-regulated in ESCC tissues compared with adjacent non-cancerous tissues in ESCC patients. Meanwhile, increased lncRNA SNHG1 expression levels markedly correlated with lymph node metastasis, depth of invasion, TNM stage and reduced over survival time in ESCC patients. Furthermore, MTT assay, colony formation, transwell cell invasion, qRT-PCR and Western-blot assays demonstrated that knockdown of lncRNA SNHG1 could inhibit cell proliferation and cell invasion capacity and cell Epithelial-Mesenchymal Transition (EMT) phenomenon by up-regulation E-cadherin and down-regulating Vimentin and N-cadherin in ESCC cells. Besides, we demonstrated that knockdown of SNHG1 suppressed the Notch signaling pathway by reducing the Notch1 and Hes-1 expression levels in ESCC cells. CONCLUSIONS These results indicated that lncRNA SNHG1 may be a potential predictor of prognosis in ESCC patients and a novel target for ESCC treatment.
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Affiliation(s)
- Yijun Zhang
- Department of Thoracic, Jilin Cancer Hospital, Changchun, Jilin, China
| | - Xintian Jin
- Department of Thoracic, Jilin Cancer Hospital, Changchun, Jilin, China
| | - Zhe Wang
- Department of Thoracic, Jilin Cancer Hospital, Changchun, Jilin, China
| | - Xiaokai Zhang
- Department of Thoracic, Jilin Cancer Hospital, Changchun, Jilin, China
| | - Shen Liu
- Department of Pharmacy, Jilin Cancer Hospital, Changchun, Jilin, China
| | - Gang Liu
- Department of Thoracic, Jilin Cancer Hospital, Changchun, Jilin, China
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Yao C, Liu HN, Wu H, Chen YJ, Li Y, Fang Y, Shen XZ, Liu TT. Diagnostic and Prognostic Value of Circulating MicroRNAs for Esophageal Squamous Cell Carcinoma: a Systematic Review and Meta-analysis. J Cancer 2018; 9:2876-2884. [PMID: 30123356 PMCID: PMC6096380 DOI: 10.7150/jca.25351] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Accepted: 06/11/2018] [Indexed: 01/08/2023] Open
Abstract
Background and Aim: MicroRNAs, dysregulated in the circulation of esophageal squamous cell carcinoma (ESCC) patient, have been assumed to be with great potential in the diagnosis and prognosis of esophageal cancer. We aimed to review previous articles on ESCC. Methods: A search of electronic databases was performed before Nov 12, 2017. We summarized the identification of microRNA imbalance in the blood of ESCC compared with the healthy controls, with the objective to evaluate the efficiency of microRNAs in diagnosing and forecasting ESCC. Results: A total of 35 studies investigating plasma or serum microRNAs were included in the meta-analysis. Based on the consequences of the quality assessment of each study, the articles involved were appropriate for quantitative synthesis. For diagnostic meta-analysis. The overall pooled sensitivity, specificity, and area under the curve of circulating microRNA is 0.794 (95% CI: 0.765 - 0.820), 0.779 (95%CI: 0.746 - 0.808), 0.86 (95%CI: 0.82 - 0.88). The diagnostic value of each microRNA was calculated respectively. For prognostic meta-analysis, the overall pooled hazard ratios of higher microRNA expression in circulation was 1.34 (95% CI: 1.14-1.58), which could significantly predict poorer survival in ESCC. Conclusions: Circulating microRNAs distinguish patients with ESCC from healthy controls with high sensitivity and specificity, compared to other invasive currently used screening methods. Simultaneously, there was prognostic value for the prognosis of ESCC.
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Affiliation(s)
- Can Yao
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
| | - Hai-Ning Liu
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
| | - Hao Wu
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
| | - Yan-Jie Chen
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
| | - Yu Li
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
| | - Ying Fang
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
| | - Xi-Zhong Shen
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China.,Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
| | - Tao-Tao Liu
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
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Zheng S, Zhang X, Wang X, Li J. Downregulation of miR-138 predicts poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Biomark 2018; 20:49-54. [PMID: 28759955 DOI: 10.3233/cbm-170079] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND MicroRNAs (miRNAs) have been proven to be critical players in many different types of tumors including esophageal squamous cell carcinoma (ESCC). OBJECTIVE This study aimed at investigating the correlation of miR-138 expression and clinical outcome of patients with ESCC. METHODS A total of 168 serum samples and 128 fresh cancer tissues as well as their corresponding adjacent non-cancerous tissues were collected. Real-time PCR was performed to evaluate the clinical value of miR-138 in ESCC. RESULTS Our results showed that tissue and serum miR-138 levels were both significantly reduced in ESCC compared to their respective controls. Tissue miR-138 levels were highly correlated with serum miR-138 levels. Serum miR-138 differentiated patients with ESCC from healthy controls with high accuracy. In addition, reduced tissue/serum miR-138 levels were correlated with unfavorable clinicopathological parameters including T stage, lymph node metastasis and TNM stage. ESCC patients with lower tissue/serum miR-138 levels had shorter five year overall survival compared with those with higher tissue/serum miR-138 levels. Finally, downregulation of miR-138 was demonstrated to be an independent prognostic risk factor for ESCC. CONCLUSIONS In conclusion, both tissue and serum miR-138 levels are reduced in ESCC, and might be promising prognostic biomarkers for ESCC.
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Shao B, Liu B, Yan C. SACMDA: MiRNA-Disease Association Prediction with Short Acyclic Connections in Heterogeneous Graph. Neuroinformatics 2018; 16:373-382. [DOI: 10.1007/s12021-018-9373-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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38
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Chen X, Yan CC, Zhang X, You ZH, Huang YA, Yan GY. HGIMDA: Heterogeneous graph inference for miRNA-disease association prediction. Oncotarget 2018; 7:65257-65269. [PMID: 27533456 PMCID: PMC5323153 DOI: 10.18632/oncotarget.11251] [Citation(s) in RCA: 182] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Accepted: 07/28/2016] [Indexed: 12/20/2022] Open
Abstract
Recently, microRNAs (miRNAs) have drawn more and more attentions because accumulating experimental studies have indicated miRNA could play critical roles in multiple biological processes as well as the development and progression of human complex diseases. Using the huge number of known heterogeneous biological datasets to predict potential associations between miRNAs and diseases is an important topic in the field of biology, medicine, and bioinformatics. In this study, considering the limitations in the previous computational methods, we developed the computational model of Heterogeneous Graph Inference for MiRNA-Disease Association prediction (HGIMDA) to uncover potential miRNA-disease associations by integrating miRNA functional similarity, disease semantic similarity, Gaussian interaction profile kernel similarity, and experimentally verified miRNA-disease associations into a heterogeneous graph. HGIMDA obtained AUCs of 0.8781 and 0.8077 based on global and local leave-one-out cross validation, respectively. Furthermore, HGIMDA was applied to three important human cancers for performance evaluation. As a result, 90% (Colon Neoplasms), 88% (Esophageal Neoplasms) and 88% (Kidney Neoplasms) of top 50 predicted miRNAs are confirmed by recent experiment reports. Furthermore, HGIMDA could be effectively applied to new diseases and new miRNAs without any known associations, which overcome the important limitations of many previous computational models.
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Affiliation(s)
- Xing Chen
- School of Information and Electrical Engineering, China University of Mining and Technology, Xuzhou, China
| | | | - Xu Zhang
- School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai, China
| | - Zhu-Hong You
- School of Computer Science and Technology, China University of Mining and Technology, Xuzhou, China
| | - Yu-An Huang
- Department of Computing, Hong Kong Polytechnic University, Hong Kong, China
| | - Gui-Ying Yan
- Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China
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Sun Q, Zong L, Zhang H, Deng Y, Zhang C, Zhang L. A 10‑microRNA prognosis scoring system in esophageal squamous cell carcinoma constructed using bioinformatic methods. Mol Med Rep 2018; 17:5222-5228. [PMID: 29393486 PMCID: PMC5865988 DOI: 10.3892/mmr.2018.8550] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Accepted: 12/14/2017] [Indexed: 12/18/2022] Open
Abstract
MicroRNA (miR) signatures may aid the diagnosis and prediction of cancer; therefore, miRs associated with the prognosis of esophageal squamous cell carcinoma (ESCC) were screened. miR‑sequencing (seq) and mRNA‑seq data from early‑stage ESCC samples were downloaded from The Cancer Genome Atlas (TCGA) database, and samples from subjects with a >6‑month survival time were assessed with Cox regression analysis for prognosis‑associated miRs. A further two miR expression datasets of ESCC samples, GSE43732 and GSE13937, were downloaded from the Gene Expression Omnibus database. Common miRs between prognosis‑associated miRs, and miRs in the GSE43732 and GSE13937, datasets were used for risk score calculations for each sample, and median risk scores were applied for the stratification of low‑ and high‑risk samples. A prognostic scoring system of signature miRs was subsequently constructed and used for survival analysis for low‑ and high‑risk samples. Differentially‑expressed genes (DEGs) corresponding to all miRs were screened and functional annotation was performed. A total of 34 prognostic miRs were screened and a scoring system was created using 10 signature miRs (hsa‑miR‑140, ‑33b, ‑34b, ‑144, ‑486, ‑214, ‑129‑2, ‑374a and ‑412). Using this system, low‑risk samples were identified to be associated with longer survival compared with high‑risk samples in the TCGA and GSE43732 datasets. Age, alcohol and tobacco use, and radiotherapy were prognostic factors for samples with different risk scores and the same clinical features. There were 168 DEGs, and the top 20 risk scores positively‑correlated and the top 20 risk scores negatively‑correlated DEGs were significantly enriched for six and 10 functional terms, respectively. 'Tight junction' and 'melanogenesis' were two significantly enriched pathways of DEGs. miR‑214, miR‑129‑2, miR‑37a and miR‑486 may predict ESCC patient survival, although further studies to validate this hypothesis are required.
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Affiliation(s)
- Qingchao Sun
- Department of Thoracic Surgery, The First Affiliated Hospital of XinJiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Liang Zong
- Department of Thoracic Surgery, The First Affiliated Hospital of XinJiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Haiping Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of XinJiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Yanchao Deng
- Department of Thoracic Surgery, The First Affiliated Hospital of XinJiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Changming Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of XinJiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Liwei Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of XinJiang Medical University, Urumqi, Xinjiang 830054, P.R. China
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Al-Khyatt W, Tufarelli C, Khan R, Iftikhar SY. Selective oestrogen receptor antagonists inhibit oesophageal cancer cell proliferation in vitro. BMC Cancer 2018; 18:121. [PMID: 29390981 PMCID: PMC5796348 DOI: 10.1186/s12885-018-4030-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 01/23/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Oestrogen receptors (ER) have a well-established role to the initiation, progression and regulation of responses to treatment of breast, prostate, and lung cancers. Previous data indicates altered ER expression in oesophageal cancers (OC). However the role of ER subtypes and ER specific inhibitors in the regulation of OC progression remains unclear. This study sought to assess levels of ERα and ERβ in OC. The effects of highly selective ER antagonists on cell proliferation and apoptosis in two OC adenocarcinoma cell lines was also studied. METHODS ERα and ERβ expression profiling in paired normal oesophageal mucosa and tumour tissues (n = 34; adenocarcinoma n = 28; squamous cell carcinoma n = 6) was performed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Correlation between levels of ER with the clinico-pathological features for OC was determined. The effect of selective ER antagonists on proliferation of OE33 and OE19 OC cell lines was studied. RESULTS ERα and ERβ mRNA expression was significantly higher (p < 0.05) in tumour tissues relative to their paired normal mucosa and correlated inversely with survival outcome (p < 0.05). Upregulation of ERα mRNA correlated with higher pathological T-stage (p < 0.05) and lymph node metastasis (p < 0.05) while ERβ mRNA upregulation correlated with positive vascular invasion (p < 0.05). A significant concentration-dependent inhibition of proliferation in OE33 and OE19 cell lines was induced by a highly-selective ERα antagonist (MPP) and an ERβ specific antagonist (PHTPP) (p < 0.05). Moreover, anti-oestrogens induced cell death through stimulation of apoptotic caspase activity. CONCLUSION These findings indicate that the ER system is involved in OC progression and thus may provide a novel target for the treatment of OC.
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Affiliation(s)
- Waleed Al-Khyatt
- Department of Upper GI Surgery, Royal Derby Hospital, Derby Teaching Hospitals NHS Foundation Trust, Uttoxeter Road, Derby, DE22 3NE UK
- Division of Medical Sciences and Graduate Entry Medicine, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT UK
| | - Cristina Tufarelli
- Division of Medical Sciences and Graduate Entry Medicine, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT UK
| | - Raheela Khan
- Division of Medical Sciences and Graduate Entry Medicine, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT UK
| | - Syed Yousef Iftikhar
- Department of Upper GI Surgery, Royal Derby Hospital, Derby Teaching Hospitals NHS Foundation Trust, Uttoxeter Road, Derby, DE22 3NE UK
- Division of Medical Sciences and Graduate Entry Medicine, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT UK
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Ma Q, Liu W, Jia R, Long H, Zhang L, Lin P, Zhao H, Ma G. Alcohol and survival in ESCC: prediagnosis alcohol consumption and postoperative survival in lymph node-negative esophageal carcinoma patients. Oncotarget 2018; 7:38857-38863. [PMID: 27095577 PMCID: PMC5122435 DOI: 10.18632/oncotarget.8754] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2015] [Accepted: 03/31/2016] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The association between esophageal cancer and prediagnosis alcohol consumption is well established. However, evidence that prediagnosis alcohol consumption affects postoperative survival in patients with lymph node-negative esophageal squamous cell carcinoma (ESCC) is lacking. We conducted a retrospective study on the effect of prediagnosis alcohol consumption on the postoperative survival of patients with lymph node-negative ESCC in China. METHODS We enrolled 643 ESCC patients with negative lymphatic metastasis who had undergone esophagectomy between 1990 and 2005 at the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China, and reviewed their demographic, pathologic, preoperative, and cancer outcome data obtained from medical records. These data were analyzed using life table and Kaplan-Meier analyses and multivariate Cox regression. RESULTS There was a significant reduction in 3- and 5-year survival in drinkers with lymph node-negative ESCC. For drinkers, 3- and 5-year survival rates were 43% and 36% respectively, whereas, for nondrinkers, the corresponding values were 63% and 58%, respectively (p < 0.05). Multivariate Cox regression showed that drinking (p = 0.001, relative risk =1.583) was an independent factor for survival in patients with lymph node-negative ESCC. Striated analysis revealed that drinking was an independent factor for survival in patients with stage II A (p = 0.008, relative risk =1.679), stage IB (p = 0.044, relative risk=1.517), and well (p=0.011, relative risk =1.783) and moderately (p = 0.002, relative risk = 1.915) differentiated ESCC. CONCLUSIONS Prediagnosis alcohol consumption is an independent prognostic factor for postoperative survival in patients with lymph node-negative ESCC.
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Affiliation(s)
- Qilong Ma
- Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wengao Liu
- Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ran Jia
- Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Hao Long
- Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Lanjun Zhang
- Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Peng Lin
- Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Hongyun Zhao
- Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Guowei Ma
- Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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Meta-analysis of microRNAs as potential biomarkers for detecting esophageal carcinoma in Asian populations. Int J Biol Markers 2017; 32:e375-e383. [PMID: 28862713 DOI: 10.5301/ijbm.5000296] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/10/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND: An Increasing number of studies in the literature have shown that microRNAs (miRNAs) can be used as early diagnostic markers for esophageal carcinoma (EC), but their conclusions remain controversial. Hence, we performed this meta-analysis to evaluate the diagnostic accuracy of using miRNAs in EC and to provide an experimental basis for early diagnosis of the disease. METHODS: This meta-analysis included 39 Asian studies from 18 articles, which covered 3,708 EC patients and 2,689 healthy controls. We used a bivariate random-effects model, the chi-square test and the I² test to assess sensitivity and heterogeneity. RESULTS: Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of miRNAs for diagnosis of EC in Asians reached 0.798, 0.785, 3.705, 0.257 and 14.391, respectively. Additionally, the area under the summary receiver operating characteristic curve was 0.86. Subgroup analysis based on research country (China vs. Japan), sample types (plasma vs. serum) and miRNAs (single vs. multiple; singly reported miRNAs vs. repeatedly reported miRNAs) showed no significant difference in accuracy of diagnosis for each subgroup. CONCLUSIONS: MiRNAs can distinguish EC patients from healthy controls. Blood-based miRNAs have better diagnostic value in detecting EC than saliva-based miRNAs, whereas both serum and plasma are recommended for clinical specimens for miRNA detection.
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Synergistic anticancer effect of combined crocetin and cisplatin on KYSE-150 cells via p53/p21 pathway. Cancer Cell Int 2017; 17:98. [PMID: 29093644 PMCID: PMC5663096 DOI: 10.1186/s12935-017-0468-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Accepted: 10/19/2017] [Indexed: 11/21/2022] Open
Abstract
Background More than 400,000 patients die from esophageal cancer annually. Considerable efforts have been made to develop new and effective treatments, one of which is directed toward herbal medication. Crocetin is a natural carotenoid dicarboxylic acid isolated from the Chinese herb saffron. We recently reported on the anticancer effects of saffron. This study aimed to determine whether crocetin combined cisplatin has synergistic effect in KYSE-150 cells and explore the underlying mechanism. Methods KYSE-150 cells were treated with crocetin and/or cisplatin. The effects on cell viability, cell apoptosis, mitochondrial membrane potential (MMP), as well as the expression levels of PI3K/AKT, MAPKs, p53/p21, and apoptosis-related protein were evaluated. MTT assay, Annexin V-FITC/PI staining, Rh123 staining, and Western blot analysis were used. Results The cell proliferation significantly decreased and cell apoptosis was induced with combined crocetin and cisplatin, compared with either crocetin only or cisplatin only. The outcome suggested that crocetin combined cisplatin has synergistic effects on inhibition of cell proliferation and pro-apoptotic effect of cisplatin on KYSE-150 cells. Disruption of MMP, upregulation of cleaved caspase-3 expression, and downregulation of Bcl-2 occurred in the group treated with combined treatment. No significant differences in p-PI3K, p-AKT, and MAPKs activity were indicated between combined treatment group and the individual treatment group. However, the expression levels of p53 and p21 were markedly higher in the combined treatment group than in the individual treatment group. The wild-type p53 inhibitor, PFT-α suppressed the overexpression of p53/p21 and the synergistic effect induced by the combination of crocetin and cisplatin. Conclusions We concluded that crocetin combined with cisplatin exerts a synergistic anticancer effect by up-regulating the p53/p21 pathway.
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Chen J, Xie L, Zheng Y, Liu C. Effects of silenced PAR-2 on cell proliferation, invasion and metastasis of esophageal cancer. Oncol Lett 2017; 14:4115-4121. [PMID: 28943918 PMCID: PMC5604181 DOI: 10.3892/ol.2017.6711] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 04/13/2017] [Indexed: 01/30/2023] Open
Abstract
The present study aimed to investigate the effect of protease-activated receptor 2 (PAR-2) on cell proliferation, invasion and metastasis in the esophageal EC109 cell line. Two short hairpin RNA (shRNA) expression plasmids were constructed based on the PAR-2 mRNA sequence in humans, and they were transfected into the EC109 esophageal cancer cell line, and the stable interference cell line (shRNA-PAR-2 EC109) was obtained by puromycin selection. Following transfection of PAR-2 shRNA-1, PAR-2 expression was significantly downregulated in mRNA level and protein level in EC109 cells (P<0.05). The proliferation of EC109 cells transfected with PAR-2 shRNA was significantly lower than the negative control group (P<0.05). At 24, 48 and 72 h, the ratio of proliferation inhibition was 15.92, 24.89 and 32.28%, respectively. Compared with the control group, S-phase arrest was observed in cells transfected with shRNA-PAR-2. The ratio of cells in the S phase was 32.79±4.06, 26.54±1.37 and 33.45±2.46% at 24, 48 and 72 h, respectively. For invasion, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.05). For metastasis assay, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.01). In the present study, the PAR-2 shRNA plasmid was constructed successfully, which can significantly downregulate PAR-2 expression in EC109 cells. Subsequent to silencing of PAR-2, the proliferation of EC109 cells was inhibited and the capabilities of invasion and migration were reduced. It is indicated that PAR-2 may be a potential target in esophageal cancer.
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Affiliation(s)
- Jinmei Chen
- Department of Gastroenterology, Affiliated Hospital of Logistics University of People's Armed Police Force, Tianjin 300162, P.R. China
| | - Liqun Xie
- Department of Gastroenterology, Affiliated Hospital of Logistics University of People's Armed Police Force, Tianjin 300162, P.R. China
| | - Yanmin Zheng
- Department of Gastroenterology, Affiliated Hospital of Logistics University of People's Armed Police Force, Tianjin 300162, P.R. China
| | - Caihong Liu
- Department of Gastroenterology, Affiliated Hospital of Logistics University of People's Armed Police Force, Tianjin 300162, P.R. China
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Silencing of Rab3D suppresses the proliferation and invasion of esophageal squamous cell carcinoma cells. Biomed Pharmacother 2017; 91:402-407. [DOI: 10.1016/j.biopha.2017.04.010] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 03/23/2017] [Accepted: 04/10/2017] [Indexed: 12/27/2022] Open
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miR-195 Regulates Proliferation and Apoptosis through Inhibiting the mTOR/p70s6k Signaling Pathway by Targeting HMGA2 in Esophageal Carcinoma Cells. DISEASE MARKERS 2017; 2017:8317913. [PMID: 28487599 PMCID: PMC5402242 DOI: 10.1155/2017/8317913] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 02/13/2017] [Accepted: 03/13/2017] [Indexed: 12/19/2022]
Abstract
miR-195 is related to tumorigenesis and frequently inhibits cell proliferation and promotes apoptosis in various cancers, including esophageal carcinoma (EC). The mTOR/p70s6k signaling pathway, which is the major target pathway for HMGA2, regulates the survival and cell proliferation of many tumors and is commonly active in EC. The relationships of miR-195, HMGA2, and the mTOR/p70s6k signaling pathway in EC, however, remain unknown. In the present study, we found that the miR-195 level was significantly downregulated in EC tissues, while the mRNA expressions of HMGA2 were significantly upregulated. Dual-luciferase reporter assay demonstrated that HMGA2 is a target of miR-195. MTT assay and flow cytometry revealed that miR-195 overexpression inhibited cell proliferation and induced apoptosis by targeting HMGA2. We also found that HMGA2 restored the inhibitory effect of miR-195 on phosphorylation of mTOR and p70S6K. Furthermore, rapamycin, a specific inhibitor of the mTOR/p70S6K signaling pathway, decreased the levels of Ki-67 and Bcl-2/Bax ratio, inhibited cell proliferation, and promoted apoptosis in EC cells. In conclusion, upregulation of miR-195 significantly suppressed cell growth and induced apoptosis of EC cells via suppressing the mTOR/p70s6k signaling pathway by targeting HMGA2.
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Liu J, Wang C, Liu X, Wang Y, Liu H, Ren G, Zhu L, Sun Z, Chen Z. Low expression of miR-1469 predicts disease progression and unfavorable post-surgical clinical outcomes in patients with esophageal squamous cell cancer. Oncol Lett 2017; 13:4469-4474. [PMID: 28588716 DOI: 10.3892/ol.2017.5957] [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: 02/16/2016] [Accepted: 01/26/2017] [Indexed: 11/06/2022] Open
Abstract
Recent studies have demonstrated that deregulated microRNA (miRNA/miR) expression has a profound impact on biological and pathological processes; abnormal miR-1469 expression was detected in several human malignancies. In the present study, the clinicopathological and prognostic significance of miR-1469 was assessed in 129 patients with esophageal squamous cell cancer (ESCC) who successfully underwent esophagectomy and esophagogastrostomy. Low miR-1469 expression was identified to be significantly associated with tumor invasion depth (P=0.026), lymph node metastasis status (P<0.001) and pathological tumor stage (P<0.001). Survival analysis demonstrated that patients with low miR-1469 expression had significantly poorer disease-free survival (DFS) (18.2 vs. 43.2%; P=0.004) and overall survival (29.1 vs. 47.3%; P=0.029) 5 years following surgery compared with patients with high miR-1469 expression. Univariate survival analysis demonstrated that low miR-1469 expression significantly predicted unfavorable 5-year DFS among patients with N1-3 disease (7.1 vs. 31.8%; P=0.043). The results from the present study indicate that miR-1469 expression could be used in the clinic to predict ESCC progression and prognosis. This will aid in the identification of high-risk patients with ESCC that require more aggressive therapeutic interventions.
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Affiliation(s)
- Jin Liu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| | - Chuifang Wang
- Department of Thoracic Surgery, Liaocheng Tumor Hospital, Liaocheng, Shandong 252000, P.R. China
| | - Xiangyan Liu
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| | - Yu Wang
- Department of Gastroenterology, Zhangqiu People's Hospital, Zhangqiu, Shandong 250200, P.R. China
| | - Haibo Liu
- Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China
| | - Guohua Ren
- Department of Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China
| | - Liangming Zhu
- Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China
| | - Zhigang Sun
- Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China
| | - Zhitao Chen
- Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China
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Wang JL, Chen Q, Wu XL, Wang Y, Hou W, Guo QZ, Chen NJ, Cheng B. Endoscopic ultrasound for preoperative staging of esophageal cancer: Application value and problems encountered. Shijie Huaren Xiaohua Zazhi 2017; 25:438-442. [DOI: 10.11569/wcjd.v25.i5.438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the value of endoscopic ultrasound (EUS) in preoperative staging of esophageal cancer and discuss the problems encountered.
METHODS A retrospective review was conducted on 388 patients with esophageal cancer who underwent EUS examination and esophagectomy from April 2014 to September 2016 at our hospital. We calculated the sensitivity, specificity and accuracy of EUS in preoperative staging of esophageal cancer and compared the characteristics of the patients with and without stenosis.
RESULTS The diagnostic accuracy of EUS for T1, T2, T3 and T4 stages was 92.8%, 82.9%, 84.5%, and 95.4%, respectively. The sensitivity, specificity and accuracy of EUS for the diagnosis of N1+ were 59.6%, 81.8% and 69.2%, respectively. In patients with stenosis, 79.5% had T3+ and 64.4% had N1+, both of which were significantly higher than those in patients without stenosis (P < 0.05).
CONCLUSION The accuracy of EUS in T staging in patients with esophageal cancer is high, and it is a reliable diagnostic tool. For patients with stenosis, pre-dilatation should be omitted and the patients should be referred for neoadjuvant therapy.
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Li Q, Zhang X, Li N, Liu Q, Chen D. miR-30b inhibits cancer cell growth, migration, and invasion by targeting homeobox A1 in esophageal cancer. Biochem Biophys Res Commun 2017; 485:506-512. [PMID: 28189678 DOI: 10.1016/j.bbrc.2017.02.016] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Accepted: 02/05/2017] [Indexed: 12/29/2022]
Abstract
Emerging evidence has shown that microRNAs (miRNAs) play important roles in tumor development and progression. In particular, miR-30b is thought to be closely related to the migration, invasion, proliferation, communication, and drug resistance of tumor cells. However, the potential value of miR-30b in human esophageal cancer (EC) remains unclear. In this study, we investigated the biological functions of miR-30b and its potential role in EC. The results indicated that the expression levels of miR-30b were decreased in EC tissues and were correlated with invasion classification (P < 0.01), lymph node metastasis (P < 0.01), and pathological stage (P < 0.05). Log-rank tests demonstrated that low expression of miR-30bwas strongly correlated with poor overall survival in patients with EC (P < 0.05). Moreover, overexpression of miR-30b markedly inhibited the growth, migration, and invasion of ECA109 and TE-1 cells by directly downregulating homeobox A1 (HOXA1). When HOXA1 was reintroduced into miR-30b-transfected ECA109 or TE-1 cells, the inhibitory effects of miR-30b on EC cell growth, migration, and invasion were markedly reversed. In conclusion, our findings demonstrated that miR-30b could inhibit tumor cell growth, migration, and invasion by directly targeting HOXA1 in EC cells.
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Affiliation(s)
- Qing Li
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medial University, Chongqing 400042, China
| | - Xuan Zhang
- Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
| | - Ning Li
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medial University, Chongqing 400042, China
| | - Qin Liu
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medial University, Chongqing 400042, China
| | - Dongfeng Chen
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medial University, Chongqing 400042, China.
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Ding Y, Ma Q, Liu F, Zhao L, Wei W. The Potential Use of Salivary miRNAs as Promising Biomarkers for Detection of Cancer: A Meta-Analysis. PLoS One 2016; 11:e0166303. [PMID: 27832115 PMCID: PMC5104484 DOI: 10.1371/journal.pone.0166303] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2016] [Accepted: 10/26/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Accumulating evidence has demonstrated that microRNAs (miRNAs) could serve as promising molecular biomarkers for cancer detection. This study aims to systematically assess the diagnostic performance of salivary miRNAs in detection of cancer through a comprehensive meta-analysis. METHODS Eligible studies were identified using PubMed and other computerized databases up to October 31, 2015, supplemented by a manual search of references from retrieved articles. The pooled sensitivity, specificity, and other measurements of accuracy of salivary miRNAs in the diagnosis of cancer were analyzed using the bivariate binomial mixed model. RESULTS Seventeen studies from 8 articles with 694 subjects were included in this meta-analysis. All studies have a relatively high score of quality assessment. The overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of salivary miRNAs in detection of cancer were 0.77 (95% confidence intervals [CI]: 0.69-0.84), 0.77 (95%CI: 0.65-0.88), 3.37 (95%CI: 2.26-5.02), 0.29 (95%CI: 0.23-0.38), and 11.41 (95%CI: 7.35-17.73), respectively. The AUC was 0.84 (95%CI: 0.80-0.87). Moreover, both whole saliva and saliva supernatant could be used as sources of clinical specimens for miRNAs detection. CONCLUSIONS Our meta-analysis demonstrated that salivary miRNAs may serve as potential noninvasive biomarkers for cancer detection. The findings need to be confirmed with further research before it can be applied in the clinic.
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Affiliation(s)
- Yuanjie Ding
- Department of Epidemiology and Health Statistics, School of Public Health, Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
| | - Qing Ma
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Fen Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China
- * E-mail: (FL); (WW)
| | - Lei Zhao
- Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA, United States of America
| | - Wenqiang Wei
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
- * E-mail: (FL); (WW)
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