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Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer and is characterized by an unfavorable prognosis. To elucidate the distinct molecular alterations in ESCC and investigate therapeutic targets, we performed a comprehensive analysis of transcriptomics, proteomics, and phosphoproteomics data derived from 60 paired treatment-naive ESCC and adjacent nontumor tissue samples. Additionally, we conducted a correlation analysis to describe the regulatory relationship between transcriptomic and proteomic processes, revealing alterations in key metabolic pathways. Unsupervised clustering analysis of the proteomics data stratified patients with ESCC into 3 subtypes with different molecular characteristics and clinical outcomes. Notably, subtype III exhibited the worst prognosis and enrichment in proteins associated with malignant processes, including glycolysis and DNA repair pathways. Furthermore, translocase of inner mitochondrial membrane domain containing 1 (TIMMDC1) was validated as a potential prognostic molecule for ESCC. Moreover, integrated kinase-substrate network analysis using the phosphoproteome nominated candidate kinases as potential targets. In vitro and in vivo experiments further confirmed casein kinase II subunit α (CSNK2A1) as a potential kinase target for ESCC. These underlying data represent a valuable resource for researchers that may provide better insights into the biology and treatment of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteômica , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Proteômica/métodos , Masculino , Camundongos , Prognóstico , Feminino , Animais , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Caseína Quinase II/metabolismo , Caseína Quinase II/genética , Transcriptoma , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , MultiômicaRESUMO
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
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Benzidamina , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Simulação de Acoplamento Molecular , Fosforilação , Proliferação de Células , Linhagem Celular Tumoral , Apoptose , Quinase 2 Dependente de CiclinaRESUMO
Subsequently to the publication of the above article, and a Corrigendum that has already been published with the intention of showing corrected versions of Figs. 3 and 6 (DOI: 10.3892/ijo.2018.4254; published online on January 24, 2018), a concerned reader drew to the Editor's attention that there appeared to be an unexpected overlap of data in a couple of the panels showing flow cytometric data in Fig. 3A; furthermore, strikingly similar data also appeared in a paper that was submitted to the journal Cancer Gene Therapy at around the same time [Zang W, Wang T, Huang J, Li M, Wang Y, Du Y, Chen X and Zhao G: Long noncoding RNA PEG10 regulates proliferation and invasion of esophageal cancer cells. Cancer Gene Ther 22: 138144, 2015]. Considering the latest discrepancies and concerns that have been raised with another of the figures in this paper, the Editor of International Journal of Oncology has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership of the Journal for any inconvenience caused. [International Journal of Oncology 46: 21632171, 2015; DOI: 10.3892/ijo.2015.2900].
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An interested reader drew to our attention that, in the above-mentioned article, there were two figures where identity in certain of the data was shared between panels within the same figure. First, in Fig. 3B, the data shown for the EC9706 cell line/negative control (NC) experiment were derived from the same original source as those for the EC-1/Blank control experiment. Secondly, in Fig. 6B the Bcl-2 bands for the two different cell lines, EC9706 and EC-1, were inadvertently duplicated (the data shown for the EC9706 cell line were correct). We have reviewed the original files and the individual figures for the submitted composite figures, and realize that the errors occurred when we produced the composite figures. The same images were accidentally inserted twice in Figs. 3 and 6 without us being fully aware of the error. We have identified all the original images, and the corrected versions of Figs. 3 and 6 are shown opposite. We regret that these errors went unnoticed prior to publication, and thank the Editor for affording us the opportunity to publish this Corrigendum. We also regret any inconvenience caused to the readership of the journal. [the original article was published in the International Journal of Oncology 46: 2163-2171, 2015; DOI: 10.3892/ijo.2015.2900].
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OBJECTIVE: To estimate the cost-effectiveness of esophageal cancer endoscopic screening once-in-a-lifetime and to predict the optimal screening age for people in high-risk areas of rural China. METHODS: A Markov model was constructed to predict and compare the effect of four esophageal cancer endoscopic screening modalities which varied with different screening ages. Long-term epidemiological effectiveness and cost-effectiveness were predicted by simulation of the model. RESULTS: Compared with the control group, strategies starting at 40, 45, 50 and 55 year-old had saved life-years of 629.51, 769.88, 738.98 and 533.21 years per 100 000 people, respectively, of which the strategy starting at 45 year-old saved the maximum life years. All strategies were cost-effective and starting at 40 year-old cost the most per life-year saved. Among all alternatives, strategies starting age at 45 year-old and 50 year-old were incremental cost-effective, and the incremental cost-effective ratios were 34 962.87 and 3 346.43 RMB per life year saved, respectively. CONCLUSIONS: The strategy starting at 40 year-old implemented at present and other strategies were cost-effective in high-risk areas of rural China. However, the 45-year-old group is more aligned with the principle of cost-effectiveness. Considering the cost-effectiveness of different strategies and social economic status, 45 year-old is regarded as the optimal starting age of esophageal cancer once-in-a-lifetime endoscopic screening and is recommended in areas lacking health resources. The strategy of starting age at 40 year-old which could obtain better screening effects would be preferable in wealthy regions.
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Neoplasias Esofágicas/diagnóstico , Esofagoscopia/economia , População Rural , Adulto , Fatores Etários , Estudos de Casos e Controles , China , Análise Custo-Benefício , Detecção Precoce de Câncer , Humanos , Cadeias de Markov , Pessoa de Meia-IdadeRESUMO
Newly discovered intrinsic regulators, the miRNAs regulate gene expression by binding to the 3'-untranslated regions of the genome. Accumulating studies have indicated that miRNAs are aberrantly expressed in various human cancers. We found that miRNA-1207-5p (miR1207-5p) was markedly downregulated in esophageal carcinoma (EC) tissues, and was correlated with EC differentiation, pathological stage and lymph node metastasis. Rates of apoptosis were increased and cell invasion ability was decreased in EC9706 and EC-1 cells transfected with a miR1207-5p mimic. Stomatin-like protein 2 (STOML-2) was predicted to be a potential target of miR1207-5p by bioinformatics analysis and this was confirmed by luciferase assay and western blotting. Our study showed that STOML-2 was negatively regulated by miR1207-5p. Furthermore, overexpression of STOML-2 abolished the miR1207-5p anti-invasion function. Based on these results, we proposed that miR1207-5p might act as a potential therapeutic target in the treatment of EC.
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Proteínas Sanguíneas/biossíntese , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Membrana/biossíntese , MicroRNAs/biossíntese , Adulto , Idoso , Apoptose/fisiologia , Proteínas Sanguíneas/genética , Western Blotting , Linhagem Celular Tumoral , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
BACKGROUND: Potential target genes of microRNA (miR)-494 have been reported in many types of cancers. However, the role of miR-494 in esophageal squamous cell carcinoma (ESCC) remains unknown. AIM: This study focused on the expression and biological function of miR-494 in ESCC. METHODS: Using bioinformatics analyses, we found that cleft lip and palate transmembrane 1-like (CLPTM1L) was a potential target of miR-494. We performed quantitative real-time (qRT) PCR assays in 37 ESCC tumor tissues to determine the expression of miR-494 and CLPTM1L mRNA, and we analyzed the correlation between both of these factors and clinical characteristics. The cell counting kit-8 and colony formation assays were used to evaluate the effects of miR-494 expression on the proliferation of ESCC cells. The transwell migration assay and flow cytometric apoptosis assay were performed to study the influence of miR-494 on the invasion and apoptosis of ESCC cells. Western blotting, luciferase assays, and CLPTM1L knockdown experiments were used to determine whether CLPTM1L was a target of miR-494. RESULTS: The qRT-PCR assays showed significant downregulation of miR-494 (P < 0.05) and upregulation of CLPTM1L mRNA (P < 0.05), both of which were significantly associated with lymph node metastases (P < 0.05). High expression of miR-494 inhibited cell proliferation and invasion and promoted cell apoptosis (P < 0.05). The results also showed that CLPTM1L was a target of miR-494. CONCLUSION: These results show that the expression of miR-494, which can regulate cell growth, invasion and apoptosis of ESCC cells by targeting CLPTM1L, is downregulated in ESCC tumor tissues. The miR-494-CLPTM1L pathway could be further exploited to develop a new approach to treat ESCC.
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Apoptose , Carcinoma de Células Escamosas/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Regiões 3' não Traduzidas , Sítios de Ligação , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Proteínas de Membrana/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Tempo , TransfecçãoRESUMO
OBJECTIVE: To summarize the endoscopic screening findings in high-risk population of esophageal and gastric carcinoma and analyze influential factors related to screening. METHODS: In seven selected cities and counties with high incidences of esophageal carcinoma, people at age of 40-69 were set as the target population. Those with gastroscopy contradictions were excluded, and all who were voluntary and willing to comply with the medical requirements were subjected to endoscopic screening and histological examination for esophageal, gastric cardia and gastric carcinoma in accordance with national technical manual for early detection and treatment of cancer. RESULTS: In three years, 36,154 people were screened, and 16,847 (46.60%) cases were found to have precancerous lesions. A total of 875 cases were found to have cancers (2.42%), and among them 739 cases had early stage with an early diagnosis rate is 84.5%. Some 715 patients underwent prompt treatment and the success rate was 81.8%. CONCLUSIONS: In a high-risk population of esophageal and gastric carcinoma, it is feasible to implement early detection and treatment by endoscopic screening. Screening can identify potential invasive carcinoma, early stage carcinoma and precancerous lesions, improving efficacy through early detection and treatment. The exploratory analysis of related influential factors will help broad implementation of early detection and treatment for esophageal and gastric carcinoma.
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Endoscopia do Sistema Digestório , Neoplasias Esofágicas/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Cárdia , China/epidemiologia , Detecção Precoce de Câncer , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/patologia , Estômago/patologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVE: To describe the temporal trends in the mortality rate of gastric cancer during the period of 1988 and 2010, and to predict the gastric cancer mortality between 2016 - 2020. METHODS: The data of gastric cancer mortality in Linzhou city between 1988 and 2010 was extracted from the cancer registry, including a total of 11 714 cases, covering 22 447 073 person-years. The mortality rate of gastric cancer of each 5-year period was calculated by sub-site and gender. Age-standardized rate (ASR) was calculated using the Chinese standard population in 1982. Intrinsic estimator (IE) model was used to fit the mortality trend by sub-site and gender, and to predict the mortality of gastric cancer in Linzhou city between 2016 and 2020. RESULTS: From 1988 to 2010, the gastric cancer mortality in Linzhou city was 52.18/100 000 (11 714/22 447 073) with the ASR at 49.23/100 000; the mortality in male was 67.02/100 000 (7678/11 455 512) with ASR at 68.68/100 000 while the mortality in female was 36.72/100 000 (4036/10 991 561) with ASR at 32.12/100 000. The mortality of cardia carcinoma was 27.87/100 000 (6257/22 447 073) with the ASR at 26.37/100 000; while the mortality of non-cardia carcinoma was 24.31/100 000 (5457/22 447 073) with the ASR at 22.86/100 000. The ASR of gastric cancer during 1988 - 1990 was 63.37/100 000 (1653 cases) and decreased by 28.34%, to 45.41/100 000 (2622 cases) during 2006 - 2010. The IE model showed that the birth cohort effect decreased greatly. The mortality risk of cardia carcinoma in population born after 1950s, decreased significantly; and the mortality risk of non-cardia carcinoma in population born in 20 century continually decreased. The death of gastric cancer among the population over 30 years old was predicted to be 3626 cases, increasing by 40.60% compared with the number between 2006 and 2010 (2579 cases). Among them, the mortality of cardia carcinoma increased by 51.89% (predicted number between 2016 and 2020 was 2456 cases, and 1617 cases between 2006 and 2010), and the mortality of non-cardia carcinoma increased by 21.62% (predicted number between 2016 and 2020 was 1170 cases, and 962 cases between 2006 and 2010). CONCLUSION: The mortality rate of gastric cancer in Linzhou city showed a decreasing trend during the period of 1988-2010, being mainly attributed to the cohort effect. However, the mortality will still increase in the future, between 2016 and 2020.
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Neoplasias Gástricas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Neoplasias Gástricas/epidemiologiaRESUMO
In recent decades, decreasing trends in esophageal cancer mortality have been observed across China. We here describe esophageal cancer mortality trends in Linzhou city, a high-incidence region of esophageal cancer in China, during 1988-2010 and make a esophageal cancer mortality projection in the period 2011-2020 using a Bayesian approach. Age standardized mortality rates were estimated by direct standardization to the World population structure in 1985. A Bayesian age-period-cohort (BAPC) analysis was carried out in order to investigate the effect of the age, period and birth cohort on esophageal cancer mortality in Linzhou during 1988-2010 and to estimate future trends for the period 2011-2020. Age-adjusted rates for men and women decreased from 1988 to 2005 and changed little thereafter. Risk increased from 30 years of age until the very elderly. Period effects showed little variation in risk throughout 1988-2010. In contrast, a cohort effect showed risk decreased greatly in later cohorts. Forecasting, based on BAPC modeling, resulted in a increasing burden of mortality and a decreasing age standardized mortality rate of esophageal cancer in Linzhou city. The decrease of esophageal cancer mortality risk since the 1930 cohort could be attributable to the improvements of social- economic environment and lifestyle. The standardized mortality rates of esophageal cancer should decrease continually. The effect of aging on the population could explain the increase in esophageal mortality projected for 2020.
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Neoplasias Esofágicas/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , China/epidemiologia , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Fatores de TempoRESUMO
AIM: To estimate the cost-benefit of endoscopic screening strategies of esophageal cancer (EC) in high-risk areas of China. METHODS: Markov model-based analyses were conducted to compare the net present values (NPVs) and the benefit-cost ratios (BCRs) of 12 EC endoscopic screening strategies. Strategies varied according to the targeted screening age, screening frequencies, and follow-up intervals. Model parameters were collected from population-based studies in China, published literatures, and surveillance data. RESULTS: Compared with non-screening outcomes, all strategies with hypothetical 100,000 subjects saved life years. Among five dominant strategies determined by the incremental cost-effectiveness analysis, screening once at age 50 years incurred the lowest NPV (international dollar-I$55 million) and BCR (2.52). Screening six times between 40-70 years at a 5-year interval [i.e., six times(40)f-strategy] yielded the highest NPV (I$99 million) and BCR (3.06). Compared with six times(40)f-strategy, screening thrice between 40-70 years at a 10-year interval resulted in relatively lower NPV, but the same BCR. CONCLUSION: EC endoscopic screening is cost-beneficial in high-risk areas of China. Policy-makers should consider the cost-benefit, population acceptance, and local economic status when choosing suitable screening strategies.
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Detecção Precoce de Câncer/economia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/economia , Esofagoscopia/economia , China , Análise Custo-Benefício , Humanos , Cadeias de MarkovRESUMO
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
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Carcinoma de Células Escamosas/genética , Cromossomos Humanos Par 2/genética , Neoplasias Esofágicas/genética , Povo Asiático/genética , China , Cromossomos Humanos Par 10/genética , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , Recombinação GenéticaRESUMO
OBJECTIVE: To analyze the trends in mortality of esophageal cancer and explore the effects of age, period and cohort on esophageal cancer mortality rate in Linzhou city in 1986 - 2010, and predict the mortality of esophageal cancer in 2016 - 2020. METHODS: All of the esophageal cancer-attributed deaths in 1986 - 2010 were drawn from the database in Center of Cancer and Vita Statistics in Henan Province. The numbers of the death cases and population were tabulated into 5-year age groups and 5-year period groups for each sex and linked each other. The age-adjusted mortality rates were calculated by direct standardization to the Chinese population structure in 1982. Intrinsic estimator model (IE model)was used to perform the age-period-cohort analysis and estimate the corresponding parameters. Age effect, period effect and cohort effect on esophageal cancer mortality rate was plotted separately. The mortality of esophageal cancer during 2016 - 2020 was predicted according to the parameters by that model. RESULTS: A total of 15432 cases died from esophageal cancer in Linzhou city in1986 - 2010. The overall crude mortality rate was 63.89 per 100, 000. Among men, the age-adjusted mortality rate was 109.66 per 100, 000 during 1986-1990 and decreased to 60.59 per 100, 000 during 2006 - 2010. For women, the age-adjusted mortality rate decreased from 74.72 per 100, 000 to 39.05 per 100, 000 at the same two calendar periods. The IE model showed that age effect was remarkable, the period effect was stable and the cohort effect decreased greatly. The predicted mortality of over 30-years old population during 2016 - 2020 is 1501 for men and 1083 for women. Compared with 2006 - 2010 period the mortality will be decreased by 6.71% and 11.08%, respectively. CONCLUSIONS: The mortality rate of esophageal cancer in Linzhou city shows a decreasing trend during the period of 1986 - 2010. This trend is mainly attributed to the cohort effect. The predicted mortality in the future will decrease continually.
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Neoplasias Esofágicas/mortalidade , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendênciasRESUMO
Minichromosome maintenance proteins are novel proliferative markers that have been proposed as diagnostic markers in many cancers. We evaluated the potential role of minichromosome maintenance protein 2 as a screening biomarker and compared it with proliferating cell nuclear antigen and Ki67 in a population survey of esophageal squamous cell carcinoma. A total of 299 esophageal samples from a high-risk region in China, including 171 from an endoscopy population survey, 30 from brushing cytology, and 98 from surgery and autopsy, underwent immunostaining with minichromosome maintenance protein 2, proliferating cell nuclear antigen, and Ki67 antibodies. Minichromosome maintenance protein 2 expression was confined to the proliferative compartment of normal and abnormal esophageal epithelium and particularly manifested in the surface layer of dysplasia and carcinoma in situ. The expression of proliferating cell nuclear antigen and Ki67 was positively correlated with that of minichromosome maintenance protein 2 (r(s) >0.39, P < .01); but their positive nuclei seldom reached the surface layer, and the labeling indices were significantly lower than those for minichromosome maintenance protein 2 in dysplasia (P < .05) and carcinoma in situ (P < .001). The sensitivity and specificity of minichromosome maintenance protein 2 in diagnosing dysplasia were 91.3% and 61.8%, respectively, higher than those for proliferating cell nuclear antigen (88.4% and 47.1%) and Ki67 (78.3% and 57.8%). Nine of 10 cancer and paracancerous surface-brushing samples expressed minichromosome maintenance protein 2, and the detection was higher than that for proliferating cell nuclear antigen (8/10 and 7/10) and Ki67 (7/10 and 7/10). However, none of 10 normal surface-brushing samples expressed the 3 markers. Minichromosome maintenance protein 2 is more sensitive and specific than proliferating cell nuclear antigen and Ki67 in indicating esophageal dysplasia. Minichromosome maintenance protein 2 immunostaining combined with surface brushing could be valuable in screening patients at high risk of cancer in mass surveys.
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Carcinoma in Situ/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Proteínas de Ciclo Celular/metabolismo , Detecção Precoce de Câncer , Neoplasias Esofágicas/diagnóstico , Proteínas Nucleares/metabolismo , Lesões Pré-Cancerosas/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/metabolismo , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/metabolismo , China/epidemiologia , Citodiagnóstico/métodos , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/metabolismo , Esôfago/patologia , Humanos , Hiperplasia , Antígeno Ki-67/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/metabolismo , Valor Preditivo dos Testes , Antígeno Nuclear de Célula em Proliferação/metabolismoRESUMO
We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.
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Povo Asiático/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Loci Gênicos , Proteínas de Membrana/genética , Fosfoinositídeo Fosfolipase C/genética , Idoso , Carcinoma de Células Escamosas/etnologia , Estudos de Casos e Controles , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 20 , Neoplasias Esofágicas/etnologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Proteínas de Membrana Transportadoras , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/fisiologiaRESUMO
OBJECTIVE: To analyze the survival level and variation of esophageal cancer in Linzhou city of Henan province from 1988 to 2004, and evaluate the effects of diagnosis and treatments on esophageal cancer in this area. METHODS: All incidence and death records for esophageal cancer during 1988 to 2004 were collected from Linzhou Tumor Registry. Cases with duplicate information or death certificate only were excluded. A total of 12,160 cases of esophageal cancer were collected, of which, 6914 cases were male, and 5246 cases were female. The sex-specific and age-specific probabilities of survival in 1992, 1997 and 2002 were calculated and linked to the data of incidence and death on esophageal cancer in this area. Five-year observed survival rate and five-year relative survival rate during 1990 to 1994, 1995 to 1999, 2000 to 2004 were calculated respectively using period survival analysis and cohort survival analysis and Z test. RESULTS: The 5-year relative survival rates among the three-episode were 28.24%, 35.24% and 40.76% respectively during 1988 to 2004. This showed an increasing trend by periods (Z values were 3.94 and 3.07, P < 0.05). The 5-year observed survival rates in men among the three-episode were 13.67%, 18.08% and 22.46% respectively, the 5-year relative survival rates were 29.94%, 36.96% and 38.40%. The 5-year observed survival rates in women among the three-episode were 15.56%, 19.29% and 28.01% respectively, the 5-year relative survival rates were 26.78%, 33.12% and 43.70%. During the two former periods, there was no significant difference in the 5-year observed survival rate and relative survival rate between men and women (Z values of observed survival rate were 1.48 and 0.88, P > 0.05. Z values of relative survival rate were 1.27 and 1.50, P > 0.05). In the third period, the 5-year observed survival rate and relative survival rate in women was higher than that in men (observed survival rate Z = 3.56, P < 0.05; relative survival rate Z = 2.09, P < 0.05). The relative survival rate that calculated using period method (respectively 35.24% and 40.76%) was higher than that using cohort method (respectively 28.77% and 33.35%) from 1995 to 1999, and from 2000 to 2004. CONCLUSION: The survival rate on esophageal cancer in Linzhou city was increasing in the three different periods. This indicated a rising status in the secondary prevention and clinical diagnosis and treatments on esophageal cancer.
Assuntos
Neoplasias Esofágicas/mortalidade , China/epidemiologia , Neoplasias Esofágicas/epidemiologia , Feminino , Humanos , Tábuas de Vida , Masculino , Análise de SobrevidaRESUMO
OBJECTIVE: Using the data on death for esophagus and stomach cancers in Linzhou cancer registration system, the mortality was described as well as the changing trend was analyzed. METHODS: 18 240 death recorders for the both cancers during 1988 to 2003 were drawn from Linzhou cancer registration system. Of which, 10138 cases were esophageal cancer and 8102 cases were gastric cancer. Then data were stratified by sex, age, year and then linked to demographic classifications. The mortalities of two topographic site cancers were calculated and the age-adjusted rates were calculated by direct standardization to the world population. The Joinpoint model was used to get the estimated annual percent change (EAPC) of the age-adjusted rates, so to estimate the death rate change trends of both cancers in population of Linzhou city. RESULTS: In 2003, the age-adjusted mortalities of esophageal cancer and gastric cancer were 68.47 per 100,000 and 57.01 per 100,000 respectively of Linzhou city. From 1988 to 2003 the death rates for both of cancers had showed the decline trends. The EAPC of the mortality for esophageal cancer was -3.82 (-4.81 - -2.82, P < 0.001) and that for gastric cancer was -2.95 (-4.16 - -1.73, P < 0.001) respectively. CONCLUSION: The declining trend in was observed the mortality of esophageal and gastric cancer in Linzhou by this study.
Assuntos
Neoplasias Esofágicas/mortalidade , Neoplasias Gástricas/mortalidade , China/epidemiologia , Feminino , Humanos , Masculino , Mortalidade/tendênciasRESUMO
OBJECTIVE: To analyze the incidence and time trends of esophageal and gastric cancers in Linzhou city bassed on the data of Linxian Tumor Registry, and to provide valid reference data for research and effective estimation of cancer control in this area. METHODS: All incidence records for the both cancers during 1988-2003 were drawn from Linzhou Tumor Registry and grouped by sex, age, year and then linked to corresponding population data. The incidence rates of those two topographic site cancers were calculated and the age-adjusted rates were calculated by direct standardization to the world population. A joinpoint model was used to get the annual percentage change (APC) of the age-adjusted rates, and to estimate the epidemiological trends of both cancers in population of Linzhou city. RESULTS: In the year 2003 the age-adjusted incidence rates of esophageal and gastric cancers were 81.78 per 100 000 and 77.08 per 100 000, respectively, in the population of Linzhou city. The incidence rate of both cancers showed a decreasing trend from 1988 to 2003. The APC of the incidence rates of esophageal cancer was - 2.6% and that of gastric cancer was - 1.8%, and both indexes were statistically significant (P < 0.05). CONCLUSION: The incidence rates of esophageal and gastric cancers have presented a decreasing trends in the population of Linzhou city. This trend will continue along with the development of social economy, elevation of living standard and improvement in living habit and environment.
Assuntos
Cárdia , Neoplasias Esofágicas/epidemiologia , Neoplasias Gástricas/epidemiologia , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Fatores SexuaisRESUMO
BACKGROUND & OBJECTIVE: Carcinoma cell embolus is a common pathological phenomenon in malignant tumors. However, there was few reports about the factors that affect the formation of carcinoma cell embolus. This study was designed to investigate the relationship between carcinoma cell embolus of esophageal or cardiac cancer and its clinical pathology. METHOD: To analyze the relations among carcinoma cell embolus, tumor invasion depth lymph node metastasis number, and cell differentiation in 59 patients with esophageal cancer and cardiac cancer. RESULTS: The relationship between carcinoma cell embolus and its formation factors were reflected as follow, there was no obvious difference among T1, T2, T3 (P > 0.05), and, quite obvious difference between T4 and T1, T2, T3 (P < 0.01). Carcinoma cell embolus is related to lymph node metastasis numbers in direct proportion and has relations with degree of carcinoma cell differentiation (P < 0.01). CONCLUSION: There was obvious relationship among tumor invasion depth, numbers of lymph node metastasis, and low-undifferentiation of carcinoma cell for carcinoma cell embolus.