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Yu XY, Chen J, Li LY, Chen FE, He Q. Rapid pathologic grading-based diagnosis of esophageal squamous cell carcinoma via Raman spectroscopy and a deep learning algorithm. World J Gastroenterol 2025; 31:104280. [PMID: 40248385 PMCID: PMC12001190 DOI: 10.3748/wjg.v31.i14.104280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/23/2025] [Accepted: 03/24/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma is a major histological subtype of esophageal cancer. Many molecular genetic changes are associated with its occurrence. Raman spectroscopy has become a new method for the early diagnosis of tumors because it can reflect the structures of substances and their changes at the molecular level. AIM To detect alterations in Raman spectral information across different stages of esophageal neoplasia. METHODS Different grades of esophageal lesions were collected, and a total of 360 groups of Raman spectrum data were collected. A 1D-transformer network model was proposed to handle the task of classifying the spectral data of esophageal squamous cell carcinoma. In addition, a deep learning model was applied to visualize the Raman spectral data and interpret their molecular characteristics. RESULTS A comparison among Raman spectral data with different pathological grades and a visual analysis revealed that the Raman peaks with significant differences were concentrated mainly at 1095 cm-1 (DNA, symmetric PO, and stretching vibration), 1132 cm-1 (cytochrome c), 1171 cm-1 (acetoacetate), 1216 cm-1 (amide III), and 1315 cm-1 (glycerol). A comparison among the training results of different models revealed that the 1D-transformer network performed best. A 93.30% accuracy value, a 96.65% specificity value, a 93.30% sensitivity value, and a 93.17% F1 score were achieved. CONCLUSION Raman spectroscopy revealed significantly different waveforms for the different stages of esophageal neoplasia. The combination of Raman spectroscopy and deep learning methods could significantly improve the accuracy of classification.
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Affiliation(s)
- Xin-Ying Yu
- Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
| | - Jian Chen
- Department of Cancer Prevention Center, Feicheng People’s Hospital, Feicheng 271000, Shandong Province, China
| | - Lian-Yu Li
- Department of Electronic Information and Communication, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Feng-En Chen
- Department of Chemistry, Tsinghua University, Beijing 100080, China
| | - Qiang He
- Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
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Che J, Zhao Y, Gu B, Li S, Li Y, Pan K, Sun T, Han X, Lv J, Zhang S, Fan B, Li C, Wang C, Wang J, Zhang T. Untargeted serum metabolomics reveals potential biomarkers and metabolic pathways associated with the progression of gastroesophageal cancer. BMC Cancer 2023; 23:1238. [PMID: 38102546 PMCID: PMC10724912 DOI: 10.1186/s12885-023-11744-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 12/12/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Previous metabolic studies in upper digestive cancer have mostly been limited to cross-sectional study designs, which hinders the ability to effectively predict outcomes in the early stage of cancer. This study aims to identify key metabolites and metabolic pathways associated with the multistage progression of epithelial cancer and to explore their predictive value for gastroesophageal cancer (GEC) formation and for the early screening of esophageal squamous cell carcinoma (ESCC). METHODS A case-cohort study within the 7-year prospective Esophageal Cancer Screening Cohort of Shandong Province included 77 GEC cases and 77 sub-cohort individuals. Untargeted metabolic analysis was performed in serum samples. Metabolites, with FDR q value < 0.05 and variable importance in projection (VIP) > 1, were selected as differential metabolites to predict GEC formation using Random Forest (RF) models. Subsequently, we evaluated the predictive performance of these differential metabolites for the early screening of ESCC. RESULTS We found a distinct metabolic profile alteration in GEC cases compared to the sub-cohort, and identified eight differential metabolites. Pathway analyses showed dysregulation in D-glutamine and D-glutamate metabolism, nitrogen metabolism, primary bile acid biosynthesis, and steroid hormone biosynthesis in GEC patients. A panel of eight differential metabolites showed good predictive performance for GEC formation, with an area under the receiver operating characteristic curve (AUC) of 0.893 (95% CI = 0.816-0.951). Furthermore, four of the GEC pathological progression-related metabolites were validated in the early screening of ESCC, with an AUC of 0.761 (95% CI = 0.716-0.805). CONCLUSIONS These findings indicated a panel of metabolites might be an alternative approach to predict GEC formation, and therefore have the potential to mitigate the risk of cancer progression at the early stage of GEC.
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Affiliation(s)
- Jiajing Che
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Yongbin Zhao
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Bingbing Gu
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Shuting Li
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Yunfei Li
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Keyu Pan
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Tiantian Sun
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Xinyue Han
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Jiali Lv
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Shuai Zhang
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Bingbing Fan
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Chunxia Li
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Cheng Wang
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
| | - Jialin Wang
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, 250117, China.
| | - Tao Zhang
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
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Oral potentially malignant disorders: clinical diagnosis and current screening aids: a narrative review. Eur J Cancer Prev 2021; 29:65-72. [PMID: 30921006 DOI: 10.1097/cej.0000000000000510] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Around 300 000 patients are estimated to have oral cancer worldwide annually, and the incidence is higher in South Asian countries. In 2005, at the Congress of WHO, the term potentially malignant disorder (PMD)/lesion was suggested as a replacement for premalignant oral lesions and conditions. PMDs are those lesions of the oral mucosa that are at an increased risk of malignant transformation compared with the healthy mucosa. PMDs consist of leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, and other miscellaneous lesions. A literature search was performed using PubMed, Scopus, and Web of Science without any language restrictions. There is no standardized method for identifying a site for biopsy and various methods such as toluidine blue stain, methylene blue, Lugol's iodine, and chemiluminescence have been proposed in the literature. Despite easy access to the oral cavity, there has been significant mortality associated with oral cancer as they are often diagnosed late because of the inability of healthcare professionals to identify them at early premalignant states. This article aims to provide healthcare professionals with the knowledge to identify potentially malignant disorders and to aid them in biopsy site identification.
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Li X, Zhao L, Wei M, Lv J, Sun Y, Shen X, Zhao D, Xue F, Zhang T, Wang J. Serum metabolomics analysis for the progression of esophageal squamous cell carcinoma. J Cancer 2021; 12:3190-3197. [PMID: 33976728 PMCID: PMC8100812 DOI: 10.7150/jca.54429] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 03/04/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND: Previous metabolomics studies have found differences in metabolic characteristics between the healthy and ESCC patients. However, few of these studies concerned the whole process of the progression of ESCC. This study aims to explore serum metabolites associated with the progression of ESCC. METHODS: Serum samples from 653 participants (305 normal, 77 esophagitis, 228 LGD, and 43 HGD/ESCC) were examined by ultra-high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS). Principal component analysis (PCA) was first applied to obtain an overview of the clustering trend for the multidimensional data. Fuzzy c-means (FCM) clustering was then used to screen metabolites with a changing tendency in the progression of ESCC. Univariate ordinal logistic regression analysis and multiple ordinal logistic regression analysis were applied to evaluate the association of metabolites with the risk of ESCC progression, and adjusted for age, gender, BMI, tobacco smoking, and alcohol drinking status. RESULTS: After FCM clustering analysis, a total of 38 metabolites exhibiting changing tendency among normal, esophagitis, LGD, and HGD/ESCC patients. Final results showed 15 metabolites associated with the progression of ESCC. Ten metabolites (dopamine, L-histidine, 5-hydroxyindoleacetate, L-tryptophan, 2'-O-methylcytidine, PC (14:0/0:0), PC (O-16:1/0:0), PE (18:0/0:0), PC (16:1/0:0), PC (18:2/0:0)) were associated with decreased risk of developing ESCC. Five metabolites (hypoxanthine, inosine, carnitine (14:1), glycochenodeoxycholate, PC (P-18:0/18:3)) were associated with increased risk of developing ESCC. CONCLUSIONS: These results demonstrated that serum metabolites are associated with the progression of ESCC. These metabolites are capable of potential biomarkers for the risk prediction and early detection of ESCC.
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Affiliation(s)
- Xia Li
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Lihong Zhao
- Tumor Preventative and Therapeutic Base of Shandong Province, Feicheng People's Hospital, Feicheng 271600, China
| | - Mengke Wei
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Jiali Lv
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yawen Sun
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China
| | - Xiaotao Shen
- Interdisciplinary Research Center on Biology and Chemistry, and Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
| | - Deli Zhao
- Tumor Preventative and Therapeutic Base of Shandong Province, Feicheng People's Hospital, Feicheng 271600, China
| | - Fuzhong Xue
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Tao Zhang
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Jialin Wang
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.,Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China
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Lin DC, Wang MR, Koeffler HP. Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients. Gastroenterology 2018; 154:374-389. [PMID: 28757263 PMCID: PMC5951382 DOI: 10.1053/j.gastro.2017.06.066] [Citation(s) in RCA: 172] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 06/05/2017] [Accepted: 06/07/2017] [Indexed: 12/28/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. The exomes of more than 600 ESCCs have been sequenced in the past 4 years, and numerous key aberrations have been identified. Recently, researchers reported both inter- and intratumor heterogeneity. Although these are interesting observations, their clinical implications are unclear due to the limited number of samples profiled. Epigenomic alterations, such as changes in DNA methylation, histone acetylation, and RNA editing, also have been observed in ESCCs. However, it is not clear what proportion of ESCC cells carry these epigenomic aberrations or how they contribute to tumor development. We review the genomic and epigenomic characteristics of ESCCs, with a focus on emerging themes. We discuss their clinical implications and future research directions.
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Affiliation(s)
- De-Chen Lin
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
| | - Ming-Rong Wang
- State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - H Phillip Koeffler
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California; Cancer Science Institute of Singapore, National University of Singapore, Singapore; National University Cancer Institute, National University Hospital Singapore, Singapore
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Fatima S, Basu R, Hallur NH. Lugol's iodine identifies dysplastic tissue in precancerous lesions: A clinical trial. Ann Maxillofac Surg 2016; 6:172-174. [PMID: 28299253 PMCID: PMC5343623 DOI: 10.4103/2231-0746.200333] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Introduction: Intraepithelial dysplasia, or “invisible” precancerous lesions, provides a challenge for visualization to the surgical team. The prognostic relevance of dysplasia and carcinoma in situ at surgical margins is well documented. Materials and Methods: We evaluated the use of Lugol's iodine in visualizing the surgical margins of dysplastic tissue by an observational study of 100 patients having oral precancerous lesions between June 2013 and March 2016. Conclusion: Lugol's iodine is a simple, inexpensive, and apparently effective means of diagnosing and visualizing the surgical margins of the dysplastic tissue in oral precancerous lesions.
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Affiliation(s)
- Shereen Fatima
- Department of Oral and Maxillofacial Surgery, Al-Badar Dental College and Hospital, Gulbarga, Karnataka, India
| | - Rajarshi Basu
- Department of Oral and Maxillofacial Surgery, Al-Badar Dental College and Hospital, Gulbarga, Karnataka, India
| | - Neelakamal H Hallur
- Department of Oral and Maxillofacial Surgery, Al-Badar Dental College and Hospital, Gulbarga, Karnataka, India
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Molecular alterations and clinical relevance in esophageal squamous cell carcinoma. Front Med 2013; 7:401-10. [PMID: 24002746 DOI: 10.1007/s11684-013-0286-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Accepted: 07/10/2013] [Indexed: 02/08/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common types of gastrointestinal cancers, and the fourth leading cause of cancer-related deaths in China. Early detection and intervention in time may dramatically increase the survival of the patients by initiating treatment regimens during earlier stages of ESCC or even during precancerous stages. Molecular classification will be useful for subtyping esophageal tumors or precancerous lesions to improve current therapeutics or early intervention of the disease. In this review, we summarize the findings in investigating the molecular alterations and clinical relevance of ESCC.
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Microsatellite analysis in multistage carcinogenesis of esophageal squamous cell carcinoma from Chongqing in Southern China. Int J Mol Sci 2011; 12:7401-9. [PMID: 22174605 PMCID: PMC3233411 DOI: 10.3390/ijms12117401] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2011] [Revised: 10/13/2011] [Accepted: 10/26/2011] [Indexed: 11/17/2022] Open
Abstract
In order to characterize the molecular events in the carcinogenesis of esophageal cancer and to identify biomarkers for the early detection of the disease, matched precancerous and cancerous tissues resected from 34 esophageal cancer patients in Chongqing of southern China were compared for the extent of loss of heterozygosity (LOH). Sixteen microsatellite markers on nine chromosome regions were used for the PCR-based LOH analysis. The overall frequency of LOH at the 16 microsatellite loci was significantly increased as the pathological status of the resection specimens changed from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and squamous cell carcinoma (SCC) (P < 0.001), indicating that tumorigenesis of the esophageal squamous epithelia is a progressive process involving accumulative changes of LOH. A total of eight markers showed LOH in the LGD samples, suggesting that these loci may be involved in the early-stage tumorigenesis of esophageal squamous cell carcinoma (ESCC) and that LOH analysis at these loci may help improve the early detection of this disease. In addition, heterozygosity was regained at four loci in the SCC samples of four patients compared with the HGD samples, suggesting the possibility of genetic heterogeneity in the tumorigenesis of esophageal cancer.
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Kanatas A, Jenkins G, Sutton D, McCaul J. Lugol's iodine identifies synchronous invasive carcinoma—time for a clinical trial. Br J Oral Maxillofac Surg 2011; 49:409-11. [DOI: 10.1016/j.bjoms.2010.07.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2010] [Accepted: 07/22/2010] [Indexed: 10/19/2022]
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Liu M, Zhang F, Liu S, Zhao W, Zhu J, Zhang X. Loss of heterozygosity analysis of microsatellites on multiple chromosome regions in dysplasia and squamous cell carcinoma of the esophagus. Exp Ther Med 2011; 2:997-1001. [PMID: 22977611 DOI: 10.3892/etm.2011.297] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2011] [Accepted: 06/16/2011] [Indexed: 12/29/2022] Open
Abstract
The objective of this study was to characterize the molecular events in the carcinogenesis of esophageal squamous cell carcinoma (ESCC) and to identify biomarkers for early detection of the disease. Matched precancerous and cancerous tissues resected from 34 esophageal cancer patients from Chongqing, southern China, were compared to evaluate the extent of loss of heterozygosity (LOH). Sixteen microsatellite markers on chromosome regions 3p, 4p, 5q, 8p, 9p, 9q, 11p, 13q and 17p were used for PCR-based LOH analysis. The overall frequency of LOH at the 16 microsatellite loci was significantly increased as the pathological status of the resection specimens changed from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and SCC (P<0.001). A total of 8 markers showed LOH in the LGD samples. In addition, heterozygosity was regained at 4 loci in the SCC samples of 4 patients, respectively, in comparison to the results for these loci in the HGD samples. The overall rate of LOH increased significantly with the deterioration of the lesions, indicating that tumorigenesis of the esophageal squamous epithelia is a progressive process involving accumulative changes in LOH. The 8 loci showing allelic loss in the LGD samples may be involved in the early-stage tumorigenesis of ESCC, and LOH analysis at these loci may help improve the early detection of this disease. Regain of heterozygosity found in certain patients suggests the possibility of genetic heterogeneity in the tumori-genesis of esophageal cancer.
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Affiliation(s)
- Ming Liu
- Departments of Cardiothoracic Surgery
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Chung CS, Lee YC, Wang CP, Ko JY, Wang WL, Wu MS, Wang HP. Secondary prevention of esophageal squamous cell carcinoma in areas where smoking, alcohol, and betel quid chewing are prevalent. J Formos Med Assoc 2010; 109:408-21. [PMID: 20610142 DOI: 10.1016/s0929-6646(10)60072-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Esophageal cancer is ranked as the sixth most common cause of cancer death worldwide and has a substantial effect on public health. In contrast to adenocarcinoma arising from Barrett's esophagus in Western countries, the major disease phenotype in the Asia-Pacific region is esophageal squamous cell carcinoma which is attributed to the prevalence of smoking, alcohol, and betel quid chewing. Despite a multidisciplinary approach to treating esophageal cancer, the outcome remains poor. Moreover, field cancerization reveals that esophageal squamous cell carcinoma is closely linked with the development of head and neck cancers that further sub-optimize the treatment of patients. Therefore, preventive strategies are of paramount importance to improve the prognosis of this dismal disease. Since obstacles exist for primary prevention via risk factor elimination, the current rationale for esophageal cancer prevention is to identify high-risk groups at earlier stages of the disease, and encourage them to get a confirmatory diagnosis, prompt treatment, and intensive surveillance for secondary prevention. Novel biomarkers for identifying specific at-risk populations are under extensive investigation. Advances in image-enhanced endoscopy do not just substantially improve our ability to identify small precancerous or cancerous foci, but can also accurately predict their invasiveness. Research input from the basic sciences should be translated into preventive measures in order to decrease the disease burden of esophageal cancer.
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Affiliation(s)
- Chen-Shuan Chung
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
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Correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma. J Genet Genomics 2009; 35:267-71. [PMID: 18499069 DOI: 10.1016/s1673-8527(08)60038-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2007] [Revised: 01/08/2008] [Accepted: 01/18/2008] [Indexed: 11/21/2022]
Abstract
Androgen-induced proliferation shutoff gene AS3, also known as APRIN, is a growth inhibitory gene that is initially implicated in prostate cancer. This gene is required for androgen-dependent growth arrest and is a primary target for 1,25(OH)(2)D(3) and androgens. Allelic loss at AS3 locus has been linked to a variety of cancers. However, the correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma (ESCC) is not well established. In this study, the genomic and expression alterations of AS3 in ESCC and their clinical significance are evaluated. Loss of heterozygosity (LOH) analysis using an AS3 intragenic microsatellite marker D13S171 revealed 72% allelic loss at AS3 locus in ESCC, which is significantly correlated with higher pathological grade (P=0.042). RT-PCR examination showed that AS3 mRNA obviously decreased in 44% tumors and its down-regulation was correlated with the sex of patients (P=0.03). Furthermore, the correlation between genomic and expression alterations of AS3 gene was analyzed in 18 ESCC specimens, which indicated that the consistency between allelic loss and decreased mRNA expression of AS3 was relatively poor. The results of this study indicate that the aberrant expression of AS3 may be involved in the tumorigenesis of esophagus and is responsible for the male predominance of ESCC.
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