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Context: Co-expressions of receptor tyrosine kinases such as c-MET and HER2 were reported in many studies. The concomitant expression is associated with more aggressive clinical course. Aims: In this study, it was intended to investigate the correlation of the positivity of c-MET and HER2 with histopathologic findings and their impacts on prognosis. Subjects and Methods: After the decision of the ethics committee, a total of 64 cases, whose HER 2 status was studied by dual silver in situ hybridization/immunohistochemistry method, were included in the study. Immunohistochemical staining for c-MET was performed to all cases and the evaluation was performed similarly to the criteria for HER2 evaluation, but cytoplasmic staining was also considered significant. Statistical Analysis Used: The data were analyzed using SPSS 20 for Windows. Results: c-MET positivity which is considered by the score of 2+ and 3+ was found only in 34.4% of HER2 positive cases while it was 59.3% in HER2 negative cases (P = 0.045). The sole histopathological feature associated with c-MET positivity was distal gastric localization (P = 0.016). Conclusions: Even though higher rates of c-MET positivity in HER2 positive cases were stated in the literature, contrary results were obtained in this study. Comparing the HER2+/c-MET + co-expression group with the other groups, no difference was found about age, sex, macroscopic and microscopic characteristics. The presence of c-MET positivity in cases with HER2 expression suggests that c-MET expression might be associated with the resistance to Trastuzumab.
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Background: NOTCH1 pathway activation has been recently described to be a key player in gastric carcinogenesis, enhance the survival and proliferation of cancer stem cells (CSCs) and mediate chemoresistance in several malignancies. Aim: This study investigated the correlation between NOTCH1 and CSC marker OCT4 (octamer binding transcription factor-4) expression and the clinicopathological properties, survival and treatment outcome in patients with gastric carcinoma (GC) receiving adjuvant chemotherapy. Materials and Methods: NOTCH1 and OCT4 were immunohistochemically detected in 50 post-operated specimens of GC. Patients' data regarding disease-free survival (DFS), overall survival (OS), and the response to the chemotherapy was statistically analyzed. Results: NOTCH1 and OCT4 overexpression was detected in 60% and 52% of GC tissues, respectively, and that was significantly higher than the rates in adjacent non-neoplastic gastric mucosa (P < 0.05). A significant correlation was detected between overexpression of NOTCH1 and OCT4 in GC and aggressive clinicopathological features; poor differentiation (P = 0.021, P = 0.037, respectively), depth of tumor invasion (P < 0.001 for both), TNM stage (P < 0.001 for both), lymph node metastasis (P = 0.002, P = 0.003, respectively) and distant metastasis (P < 0.001 for both). NOTCH1 was positively correlated with OCT4 (P = 0.002). Survival analysis disclosed that upregulation of NOTCH1 and OCT4 was associated with worse DFS (P = 0.013, P < 0.001, respectively) and OS (P < 0.001 for both). Overexpression of NOTCH1 and OCT4 correlated with poor response to chemotherapy (P = 0.013, P = 0.005, respectively) and worse clinical outcome. Conclusion: Combined detection of these proteins might disclose even better predictive value for shorter survival and resistance to chemotherapy.
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Objective:To establish a method of serum detection by Raman spectroscopy for the diagnosis of gastric cancer.Methods:Between April and November 2019, 110 patients with gastric cancer [73 males, 37 females, age (57.4±10.3) years] and 74 patients with colorectal cancer [48 males and 26 females, aged (58.3±12.2) years] were collected at the First Affiliated Hospital of Army Military Medical University, along with 100 healthy subjects [59 males and 41 females, aged (55.6±10.61) years] during the same period. Fasting venous blood serum samples were collected from the subjects. A Raman spectrometer XploRA PLUS was used in this experiment, with an excitation light source of 532 nm, a field of view of 100 times, and a spectrum range of 200-2 000 cm -1, etc. The serum samples were detected by nondestructive and non-contact rapid detection, and the Raman spectra of serum samples were collected. Using the Raman spectrum acquisition and processing supporting software LabSpec6 to smooth, baseline, and normalize the obtained Raman spectrum. Multivariate statistical analysis software SIMCA14.1 were applied to import and analyze the obtained Raman spectrum data by principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and other methods for statistical analysis. An operating characteristic curve (ROC) was constructed to evaluate the model analysis effect between serum samples of healthy people and those with gastric cancer. Serum samples from the colorectal cancer group were used to verify the reliability of the model. Results:Six Raman peaks with good repeatability were detected in serum samples in health and gastric cancer group, and peaks were located at 1 001.17, 1 154.63, 1 337.89, 1 446.85, 1 515.33, and 1 658.34 cm -1, respectively. Raman intensities at six Raman peaks were significantly different between healthy and gastric cancer groups. At the displacement of 1 001.17, 1 154.63, and 1 515.33 cm -1, the Raman intensity in the healthy group was higher than that in the gastric cancer group. At 1 337.89, 1 446.85, and 1 658.34 cm -1 displacement, the Raman intensity of the gastric cancer group was higher than that of the healthy group. An OPLS-DA model was constructed to analyze the serum samples of the healthy group and the gastric cancer group. In the model, R 2 is the fitting power, and Q 2 is the predictive ability. The closer the values of R 2 and Q 2 are to 1, the better the performance of the model, and the obtained model's R 2X(cum)=0.809, R 2Y(cum)=0.819, Q 2(cum)=0.758. ROC characteristic curve was drawn based on the OPLS-DA model. The area under the curve (AUC) of the gastric cancer group was 0.998. Six peaks with good repeatability were detected in the serum Raman spectra of gastric cancer stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ, which were located at the displacement of 1 001.85, 1 155.07, 1 338.36, 1 445.75, 1 515.92, and 1 657.68 cm -1, respectively, and at the displacement of 1 155.07 and 1 515.92 cm -1. The Raman intensity of gastric cancer stage Ⅳwas significantly higher than that of gastric cancer stages Ⅰ, Ⅱ, and Ⅲ. Conclusions:According to the model reliability verification, the healthy group, gastric cancer group and colorectal cancer group can also be effectively separated based on OPLS-DA results; it showed a good performance in separating the healthy group from the gastric cancer group. It is possible to detect serum samples from healthy people and gastric cancer patients unlabeled by combining Raman spectroscopy and the OPLS-DA method in multivariate statistics.
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Objective @#The CRISPR / dCas9-SAM system was used to explore genes related to the proliferation of gastric cancer cells AGS,and their role in the occurrence and development of gastric cancer was analyzed.@*Methods @#sgRNA was designed for genes with differential expression between gastric cancer and normal gastric tissue, and a lentiviral library was obtained after packaging was constructed.The AGS cells at different time points after the library was infected with AGS cells were used as the screening pressure,and the AGS cells at three time points on days 0,7 and 14 were collected.High-throughput sequencing analyzed sgRNA enrichment in AGS cells at dif- ferent time points after infection to obtain differential genes related to AGS cell proliferation. @*Results @#Bioinformat- ics showed that compared with the 0 d group,42 and 45 negative screening differential genes and 59 and 40 posi- tive screening differential genes were obtained in the 7 d group and 14 d group,respectively.Among them,the 7 d group and the 14 d group had 11 genes in the negative screening and the positive screening.@*Conclusion @#In this study,11 genes inhibiting the proliferation of AGS cells were screened,of which 5 were protein-coding genes and 6 were long non-coding RNA ( lncRNA ) genes. 11 candidate genes that promoted AGS cell proliferation were screened,of which 3 were protein-coding genes and 8 were lncRNA genes.It laid a foundation for further function- al verification and comprehensive analysis of the occurrence and development process of gastric cancer.
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Objective To compare the dosimetric characteristics of non-coplanar and coplanar field technology in static intensity-modulated radiotherapy of gastric cancer patients, so as to provide a reference for clinical radiotherapy plan selection. Methods Thirty-six patients with gastric cancer were selected to receive intensity-modulated radiotherapy in Huanggang Central Hospital, which was designed plan A and B. Group A used 7-field coplanar technology, while Group B used 7-field non-coplanar technology. We compared the differences of the optimized monitor unit, the dosimetry of organs at risk and target areas between group A and group B. Results Both group A and B could meet the requirements of doctors. The homogeneity index (0.14 ± 0.02), the conformity index (0.98 ± 0.01), Dmin (4315.21 ± 16.74) cGy、Dmean (4679.28 ± 28.39) cGy and Dmax(4952.30 ± 33.26) cGy of target areas in group B were better than those of group A. Moreover, the monitor unit of group B was much lower than that of group A, and the difference was statistically significant (P < 0.05). The Dmax, Dmean, V15, V20 and V30 of the left and right kidneys in group B were lower than those of group A. The Dmax (3408.57 ± 46.03) cGy, Dmean (1250.32 ± 14.27) cGy and V20 (44.91% ± 6.67%) of spinal cord and the Dmax (3408.57 ± 46.03) cGy, Dmean (1720.55 ± 17.42) cGy, V20 (25.31% ± 7.78%) and V30 (18.52% ± 1.56%) of small intestine were also lower than those of group A. The differences were statistically significant (P < 0.05). Conclusion The non-coplanar field radiation plan has more advantages in terms of target dose distribution and protection of organs so that it can be more considerably used in the process of planning and design.
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Introducción: El Helicobacter pylori se ha relacionado con el desarrollo de gastritis crónica atrófica, metaplasia intestinal y displasia, lesiones que pueden evolucionar a carcinoma gástrico. Existen investigaciones que demuestran que la erradicación de esta bacteria disminuye el riesgo de progresión histopatológica de las lesiones preneoplásicas, excepto la metaplasia intestinal y la displasia. Se realizó una revisión de los artículos publicados en las bases de datos Pubmed, Scielo, Medline y Cochrane, relacionados con el tema. Objetivo: Profundizar en los conocimientos relacionados con la infección por Helicobacter pylori y cáncer gástrico. Desarrollo: El adenocarcinoma es el tumor gástrico más frecuente y el Helicobacter pylori es el agente etiológico principal. En poblaciones de riesgo elevado, el adenocarcinoma gástrico de tipo intestinal, se precede de lesiones preneoplásicas (atrofia, metaplasia intestinal y displasia) que evoluciona al cáncer invasor. Conclusiones: Helicobacter pylori favorece la carcinogénesis gástrica, aunque existen otros factores de riesgo para el surgimiento del cáncer gástrico como son: la historia familiar, la pobre ingestión de frutas y vegetales y el bajo nivel socioeconómico(AU)
Introduction: Helicobacter pylori has been linked to the development of chronic atrophic gastritis, intestinal metaplasia, and dysplasia, lesions that can progress to gastric carcinoma. There is research showing that the eradication of this bacterium reduces the risk of histopathological progression of preneoplastic lesions, except for intestinal metaplasia and dysplasia. A bibliographic review was made of the articles published in the Pubmed, Scielo, Medline and Cochrane data bases, related to the topic, belonging to authors dedicated to the study of this problem. Objective: To go deepen in the knowledge related to Helicobacter pylori infection and gastric cancer. Development: Adenocarcinoma is the most frequent gastric tumor and Helicobacter pylori is the main etiologic agent. In high-risk populations, gastric adenocarcinoma of the intestinal type, is preceded by preneoplasic lesions (atrophy, intestinal metaplasia, and dysplasia), that progresses to invasive cancer. Conclusions: Helicobacter pylori favors gastric carcinogenesis, although there are other risk factors for the development of gastric cancer such as: family history, poor intake of fruits and vegetables, and low socioeconomic leve(AU)
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Humanos , Neoplasias Gástricas/epidemiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológicoRESUMO
Introduction: Gastric carcinoma is an aggressive malignancy with non-specific early symptoms. It is the second most commoncause of cancer-related deaths in the world.Materials and Methods: All cases of gastric carcinomas aged <40 years presented at Sri Ramachandra Institute of HigherEducation and Research from January 2016 to December 2019 were included in this study. The presenting symptoms andoutcome were collected from medical records. Pathology reports of the included cases were retrieved and associated factorswere analyzed.Results: Out of the 177 known cases of gastric carcinoma, 17 were under the age of 40 (9.6%), out of which, 10 (58.8%)were female and 7 (41.7%) were male. The number of males was higher in the patients >40 years. Fourteen cases (82.3%)were between 30 and 40 years. Three cases (17.6%) were between 20 and 30 years of age. Helicobacter pylori associatedgastritis was seen in 6 cases (35.2%). Out of the 17 cases (41.1%), 7 were poorly differentiated. The distal stomach was thesite of the tumor in 15 cases (88.2%), 2 cases were present in the gastroesophageal junction. The most common presentingcomplaints of these patients were abdominal pain, abdominal distension, vomiting associated with food intake, and constipation,with the duration of these symptoms being 1–6 months. Two patients (11.7%) had a positive family history. Three patients(17.6%) had a positive history of substance abuse. Five patients reported a history of loss of weight and appetite. One patienthad metastasis to the liver, one to the liver, bone, and lungs, and one to the liver and esophagus. Ten patients (58.8%) weretreated with gastrectomy (subtotal/distal/partial) and two patients with esophageal gastrectomy. Most of the patients were givenchemotherapy and one was given palliative chemotherapy and radiotherapy.Conclusion: Tumors rarely occur in the young, hence malignancy is not suspected and diagnosis is delayed. This leads to ahigher mortality rate as patients present with advanced stage of the disease. This study highlighted the “shift in trend” of incidenceof gastric carcinomas in younger age group. Screening and early diagnosis and treatment are essential for young patients.
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Background: Presence of H. pylori infection was found associated with peptic perforation and gastric carcinoma. Present study tried to estimate the prevalence of H. pylori infection in those patients and to find out the correlates of H. pylori infection.Methods: After matching the inclusion and exclusion criteria, all cases of diagnosed peptic perforation and gastric carcinoma were taken for this prospective, single center, observational study.Results: Among the study population, gastric carcinoma was found in higher age group; whereas peptic perforation was found in lower age group; male and female ratio was 2:1 in both groups of patient. Laborer and housewives were mostly affected in both cases. Gastric carcinoma was more prevalent in urban residents, opposite was seen in peptic perforation. Most patients in two groups had no previous co-morbid condition. Use of NSAIDs was found in high frequency in both groups. Most of the patients were chronic alcoholic and chronic smoker, and most of them had history of taking spicy foods more than twice in a week.Conclusions: H. pylori infection was found in high frequency in both group of patients, and it was higher in peptic perforation. The study establishes the association of H. pylori with the gastric carcinoma and peptic perforation.
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Gastric carcinoma, gastrointestinal stromal tumor and gastric neuroendocrine tumor are the most common gastric neoplasms. A series of researches in 2019 showed that the safety and efficacy of laparoscopic gastrectomy in the treatment of both early and advanced gastric cancer patients are similar to open surgeries, providing a high-level evidence-based medical basis for the promotion of laparoscopic surgery in the treatment for gastric cancer. In multidisciplinary treatment and perioperative chemoradiotherapy, major research results have also been published, and clinical researches in China are gradually gaining international recognition and attention. Although the application of targeted therapy and immunotherapy has made progress, the first-line therapy after gastric cancer surgery has not been established. In the field of gastrointestinal stromal tumors, laparoscopic surgery has gradually been recognized, and surgical treatment of patients with advanced drug resistance still has its value. In terms of gastric neuroendocrine tumors, the latest researches showed that surgical methods should be selected according to tumor characteristics, and gastric adenocarcinoma with neuroendocrine components may have a worse prognosis.
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Objective To investigate the effect of gambogic acid (GA) on invasion in human gastric carcinoma SGC-7901 cells and its possible mechanism. Methods Cell counting kit-8(CCK-8) assay was performed to detect the effects of GA, inhibitor of nuclear factor kappa-B kinase( IKK) 16 and 5-fluorouracil (5-FU) on cell activity of GES-1 and SGC-7901 cells. Cell invasion was assessed with Transwell invasion assay. Western blotting was used to analyze the protein levels of vimentin, matrix metalloproteinase 2 ( MMP-2) and MMP-9 and protein phosphorylation of IKKα and p65. Results The cell activity was significantly decreased in SGC-7901 cells treated with GA in a dose-dependent manner with a half inhibiton concentration(IC50) value of 1. 89 μmol/L. But GA had no significant influence on cell viability of GES-1 cells. Meanwhile, 5-FU reduced the cell activity of GES-1 and SGC-7901 cells with IC50values of 7.36 μmol/L and 199.57 μmol/L respectively. Low-dose GA and IKK 16 impaired separately the ability of invasion in SGC-7901 cells, and down-regulated the protein levels of MMP-2, MMP-9 and vimentin, and inhibited phosphorylation of IKKot and p65, while a stronger inhibition was showed when the combination of GA and IKK16 was used. Conclusion Low-dose GA might inhibit invasion of SGC-7901 cells via IKKot/p65 signaling pathway.
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Syndrome of inappropriate antidiuretic hormone secretion (SIADH) results in impaired water excretion and consequent water intoxication and hyponatremia. In patients with cancer, SIADH is most commonly driven by ectopic ADH production, a paraneoplastic syndrome frequently seen in small cell lung cancer. A 63 year old male presented with loss of appetite, vomiting and hiccups. No abnormalities were detected on physical examination. Upper gastrointestinal endoscopy showed a proliferative growth in the stomach and histopathology report confirmed gastric adenocarcinoma. His laboratory investigations revealed low serum sodium and further work up for SIADH confirmed the diagnosis. The patient was treated with hypertonic saline and he improved symptomatically. He was subsequently treated with two cycles of capecitabine and oxaliplatin. The patient was asymptomatic and maintained a serum sodium in the range of 120 to 130 mEq/L, with a serum sodium of 127 mEq/L on follow up.
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Background: Carcinoma of stomach is the second mostcommon cancer in developing countries after lung in males.Chile, Costa Rica, Japan, China and former Soviet Union hasthe highest reported death rate.Subjects and Methods: The present study is a Retrospectivestudy and the study period was between October 2015 toSeptember 2018. The age as an inclusion criterion was 30years above reporting with histopathological diagnosis ofgastric carcinoma to determine the age at presentation, stageat presentation, gender distribution, type of surgery done andthe common histopathological diagnosis.Results: Highest incidence of 27.6%in the age group 40-49years, 23.7% in 30-39 years, 22.4% in 50-59 years, and 18.4%in 60-69 years and 9.2% in >70 years, beyond 70 years theincidence decreases.Conclusion: To conclude the present study showed a highincidence in the age group 40 to 49yrs and the most commonaffected gender was male. Pylorus and Pyloric antrum werethe common site of presentation. Most of the patient around59.2% presented in a locally advanced stage.
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Gastric cancer is the one of human tumor disease that is directly related to bacterial infection disease. Helicobacter pylori(Hp)is a cancer-causing pathogen, whose prevalence rate in the population is as high as 50%. The indications for Hp eradication have been developong; however, for infected people, especially for the asymptomatic infection group, it remains controversial whether to perform the eradication therapy. This review describes the cost-effectiveness of eradicating Hp and the prevention and treatment of gastric cancer,based on the current situation of health care in China and from the perspective of health economics, so as to provide some ideas for the prevention and treatment of gastric cancer with domestic Hp infected people.
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@# 【Objective】To investigate the effects of Epstein-Barr virus(EBV)on proliferation,apoptosis and lipid metabolism of gastric cancer cells,revealing the pathogenesis and development of EBV-associated gastric carcinoma (EBVaGC).【Methods】EBV-positive cell line AGS-EBV was established by co-culturing AGS and Akata. Then we compared proliferation,apoptosis and lipid metabolism level between AGS and AGS-EBV cells. CCK-8 assays and Annexin V PE/7-AAD assays were performed to determine the proliferation and apoptosis of gastric cancer cells. Oil-Red O staining and three kinds of kits were used to detect lipid contents including lipid droplets,free fatty acid,triacylglycerol and total cholesterol. Key enzymes of lipogenesis were measured by qRT-PCR.【Results】EBV promoted the proliferation of gastric cancer cell line AGS(F = 23.214,P = 0.001;P values of 24 h,48 h,72 h,96 h and 120 h were 0.007, 0.004,<0.001,<0.001 and <0.001,respectively),inhibited apoptosis(P values of late and total apoptotic rates were 0.032,< 0.001),and increased intracellular lipid droplets,free fatty acids(P < 0.001),triacylglycerol(P = 0.004) and total cholesterol(P < 0.001)probably via lipogenesis. 【Conclusions】EBV promotes proliferation,inhibits apoptosis, and enhances lipid metabolism of gastric cancer cells.
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Objective Prognoses of late stage signet-ring cell carcinoma (SRCC) is usually worse than that in other gastric carcinoma. In the current study, SEER database were adopted to analyze the clinicopathologic features and prognoses of SRCC and non-signet-ring cell carcinoma (non SRCC), and to compare the differences in survival rate under different early treatments. Methods Clinical data of 5193 patients who were diagnosed with gastric carcinoma from 2010 to 2015 are collected from SEER. Patients are divided into two groups SRCC (n=2439) and non SRCC (n=2754) based on their histologic type. Differences in Gender, age, race, primary site, degree of differentiation, tumor size, depth of invasion, local lymph node metastasis, distant metastasis, tumor, node, metastasis (TNM) staging, operative treatment and chemotherapy were compared. Cox regression model was used to analyze prognostic factors. According to different operative treatment, patients in SRCC and non SRCC groups were divided into surgery group and surgery with adjuvant chemotherapy group, respectively. Kaplan-meier method was used to draw the survival curve, and Log-Rank test was adopted for survival analysis. Results Significant statistical difference (P<0.05) were found in the two gastric carcinoma groups regarding gender, age, race, primary site, degree of differentiation, tumor size, depth of invasion, local lymph node metastasis, distant metastasis, TNM staging, operative treatment and chemotherapy. The multivariate Cox regression analysis indicated that age (HR:1.417; 95%CI:1.273-1.578; P<0.05), race (HR:0.91; 95%CI:0.825-0.998; P<0.05), tumor size (HR:1.28; 95%CI: 1.199-1.365; P<0.05), depth of invasion (HR: 1.252: 95%CI: 1.159-1.352; P<0.05), local lymph node metastasis (HR:0.862; 95%CI: 0.81-0.918; P<0.05), distant metastasis (HR: 1.369: 95%CI: 1.069-1.753; P<0.05), TNM stage (HR:1.342; 95%CI:1.155-1.559; P<0.05), and surgical treatment (HR:0.245; 95%CI: 0.228-0.284; P<0.05) are independent risk factors affecting the prognosis of SRCC patients. The overall five-year survival rate of SRCC patients is 27.6% , which is lower than that of non SRCC patients (43.0%). Therefore, there is significant difference in statistics (P<0.05). Significant statistical difference was also found in stratification analysis of the five-year survival rates among SRCC surgery group, SRCC surgery with adjuvant chemotherapy group, non SRCC surgery group and non SRCC surgery with adjuvant chemotherapy group. The results indicated that the five-year survival rates of SRCC surgery with adjuvant chemotherapy group at stage TIN1M0 and stage T2N0M0 are both superior to that in the surgery group with statistical difference (P<0.05). In addition, the five-year survival rate of SRCC surgery with adjuvant chemotherapy group at T2N0M0 is superior to that in the non SRCC patients, with statistical difference (P<0.05). Conclusion SRCC patients present with unique clinicopathologic features. Early detection and treatment could improve the prognosis of SRCC patients.
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OBJECTIVE@#To develop a fiber Raman endoscopic probe that can be integrated in a gastroscope and evaluate its value in the diagnosis of gastric cancer.@*METHODS@#The Raman spectra of gastric cancer tissues and normal tissues were obtained using the fiber Raman endoscopic probe and confocal microRaman spectroscopy. After preprocessing with smoothing, baseline elimination and normalization, the spectroscopic data were analyzed by the principle component analyses combined with stechiometry. Based on the pathological results, the diagnostic accuracy, sensitiveness and specificity of Raman spectroscopy combined with stechiometry were evaluated.@*RESULTS@#The fiber Raman endoscopic probe and microRaman spectroscopy revealed significantly different Raman spectra between gastric cancer tissues and normal tissues. The diagnostic accuracy, sensitiveness and specificity of the fiber Raman endoscopic probe was 80.56%, 88.89%, and 84.72% for gastric cancer, respectively.@*CONCLUSIONS@#The fiber Raman endoscopic probe combined with stechiometry provides an effective modality for the diagnosis of gastric cancer and can well distinguish gastric cancer tissue from normal gastric tissues.
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Humanos , Endoscopia , Tecnologia de Fibra Óptica , Sensibilidade e Especificidade , Análise Espectral Raman , Neoplasias GástricasRESUMO
To explore the molecular mechanism underlying gastric carcinogenesis and progression by using gene expression profiling array together with bioinformatics. Lentivirus short hairpin RNA targeting STIL(ShSTIL)and scrambled sequence RNA(ShCon)were transduced into the gastric cancer cell line SGC-7901.RNA extraction,complementary DNA synthesis,construction of biotin-labelled amplified RNA probes,and hybridization with gene expression profile were consecutively performed.We collected corresponding data and analyzed differentially expressing genes(DEGs),followed by the analysis of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment,transcription factor regulating network,and protein-protein interacting networks. Compared with ShCon,a total of 417 and 87 genes were respectively down-regulated and up-regulated,respectively,in the ShSTIL group(1 or <-1).GO and KEGG enrichment analysis indicated that genes regulated by STIL were localized in cytoplasm,extracellular exosome,Golgi apparatus and various biomembranes,and were implicated in the ubiquitin-mediated proteolysis,P53 signaling pathway,and pathways regulating pluripotency of stem cells.Evaluation on genes enriched in KEGG pathways,regulation of transcription factors,and protein-protein interacting network demonstrated that IGF1R,STUB1,SKP2,and FOXO1 were localized at the centre of the network and played a key role in the development and progression of gastric cancer. Through the protein-protein interactions,STIL may activate E3 ubiquitin ligase STUB1 or SKP2,promote the proteolysis of FOXO1-a transcription factor,regulate the expression of IGF1R,and thus promote gastric carcinogenesis and progression.
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Humanos , Biologia Computacional , Perfilação da Expressão Gênica , Ontologia Genética , Neoplasias Gástricas , Genética , TranscriptomaRESUMO
Objective To investigate the relationship between the expression of ASPP2 mRNA and the methylation of ASPP2 gene in gastric cancer cells,to observe the inhibitory effect of 5-Aza-CdR on the growth of gastric cancer cells,to observe the effect of demethylation on the expression of ASPP2 mRNA and the methylation of ASPP2 gene in gastric cancer cells,and to explore the molecular mechanism of gastric cancer.Methods Real-time PCR was used to detect the expression of ASPP2 mRNA in two gastric cancer cells and normal gastric epithelial cells.BSP was used to detect the methylation of ASPP2 gene in two gastric cancer cells and normal gastric epithelial cells.CCK-8 was used to detect the growth inhibition rate of gastric cancer cells treated with 5-Aza-CdR of different concentrations,then they were used to detect expression of ASPP2 mRNA and the methylation of ASPP2 gene in gastric cancer cells again after the demethylation.Results ① The expression of ASPP2 mRNA in MKN-45 cells was significantly lower than that in GES-1 cells(P<0.01).The expression of ASPP2 mRNA in MGC-803 cells was significantly lower than that in GES-1 cells (P<0.01).There was no significant difference in MGC-803 cells and MKN-45 cells(P>0.05).② The methylation rate of ASPP2 in MKN-45 cells was significantly higher than that in GES-1 cells (P<0.01).The methylation rate of ASPP2 in MGC-803 cells was not significantly different from that in GES-1 cells (P>0.05).The methylation rate of ASPP2 in MKN-45 cells was significantly higher than that in MGC-803 cells (P<0.01).③ At the same time,the growth inhibition rate of each 5-Aza-CdR concentration group increased as the drug concentration depended.4.The expression of ASPP2 mRNA in MKN-45 cells was significantly higher than that before treatment (P<0.01),the expression of ASPP2 mRNA in MGC-803 cells was not significantly different from that before treatment(P>0.05).The methylation rate of ASPP2 in MKN-45 cells was significantly lower than that before treatment (P<0.01).The methylation rate of ASPP2 in MGC-803 cells was not significantly different from that before treatment (P>0.05).Conclusion ① Abnormal hypermethylation of ASPP2 gene in MKN-45 cells may be a molecular mechanism of decreased ASPP2 mRNA expression.② 5-Aza-CdR can inhibit the growth of MKN-45 and MGC-803 cells,and it can enhance the expression of ASPP2 mRNA in MKN-45 cells.Reversal of methylation in the promoter region of ASPP2 gene is the possible mechanism.③ Abnormal hypermethylation of the promoter region of ASPP2 gene may lead to silencing of mRNA expression that may be associated with gastric cancer.
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@# To investigate the role of long chain non-coding RNA00707 (lncRNA00707) and micro RNA-613 (miR-613) in regulating the proliferation and metastasis of gastric cancer cells and its underlying mechanisms. Methods: Eighty-nine pairs of primary gastric cancer tissues and corresponding prar-cancerous tissues were collected from the Department of Surgical Oncology, Qinghai Provincial People's Hospital during January 2014 and June 2018 for this study. The expressions of lncRNA00707 and miR-613 in gastric cancer tissues and cells were detected by qPCR. The lncRNA00707 low expression and over-expression models of MGC-803 and SGC-7901 cells were established; The proliferation of gastric cancer cells was monitored by CCK-8 assay, and Transwell assay was performed to determine the migration and invasion of gastric cancer cells. Dual luciferase gene reporter assay was adopted to validate the relationship between lncRNA 00707 and miR-613. Results: Compared with para-cancerous tissues and normal cell line GES-1, the expression of lncRNA 00707 was significantly up-regulated in cancer tissues and cell lines, and the expression of lncRNA00707 was positively correlated with WHO stage (all P<0.05). Down-regulation of lncRNA 00707 significantly inhibited the proliferation and migration of SGC-7901 cells, while overexpression of lncRNA00707 exerted the opposite effect (all P<0.05). Compared with negative control group, lncRNA00707 over-expression significantly reduced the luciferase activity of miR-613; in the contrary, the luciferase activity of miR-163 was significantly increased in MGC-803 and SGC-7901 cells with lncRNA 00707 knockdown (all P<0.01). Conclusion: lncRNA 00707 facilitates the proliferation, migration and invasion of gastric cancer cells by inhibiting the function of miR-613, which exerts a protumorigenic effect in gastric cancer.
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@# Objective: To evaluate the potential associations between the single nucleotide polymorphisms (SNPs) of lncRNA H19 genes and the susceptibility to gastric cancer (GC), especially to EBV-associated gastric cancer (EBVaGC) in Han population in Qingdao. Methods: 225 cases of pathologically confirmed fresh gastric cancer tissues or paraffin embedded gastric cancer tissues during January 2015 and October 2018 were collected from Affiliated Hospital of Qingdao University, as GC group; in the meanwhile, 200 healthy people underwent physical examination at Outpatient were collected as control. The 225 cases of cancer tissues were assigned into two groups according to the transcription result of EBV-encoded small molecule non-polyadenylation (EBER 1) by In situ hybridization: EBVaGC group (70 cases) and EBVnGC group (155 cases). DNA was extracted from the tissues of two groups and peripheral blood of healthy participants.According to the general setting of HaploView software (MAF>0.05, r2>0.8), four TagSNPs (rs217727, rs2735971, rs2839698 and rs3741216) of H19 were screened. Genotyping of each SNP locus was carried out by using Taq-Man MGB allele typing kit, and the gene polymorphisms were examined. Results: H19 SNPs of collected tissue samples were in accordance with the HardyWeinberg equilibrium. Compared with control group, patients carrying TT genotype of H19 rs217727 loci had significantly increased susceptibility to gastric cancer (χ2=9.073, P=0.003, OR=1.999, 95% CI=1.271-3.143), so did the T allele (χ2=13.475, P=0.001, OR= 1.661, 95% CI=1.266-2.180). In contrast, patients carrying TC and CC genotype of rs2839698 loci had significantly increased susceptibility to gastric cancer (χ2=9.407, P=0.002; χ2=6.517, P=0.011), and patients carrying C allele had obviously increased susceptibility to GC (χ2=6.163, P=0.013, OR=1.417, 95%CI=1.076-1.867; χ2=9.542, P=0.02, OR=2.070, 95%CI=1.298-3.302).As for the rs2735971 and rs3741216, there was no significant difference between the GC group and the control group (all P>0.05). The distribution of 4 H19 SNPs showed no statistical difference in both EBVaGC group and EBVnGC group (all P>0.05). Conclusion: There was an association between H19 gene polymorphism (rs217727 and rs2839698) and gastric carcinoma; patients carrying the TT genotype of rs217727 and C allele of rs2839698 may increase the risk of gastric carcinoma. No significant association was observed between H19 SNP polymorphism and risk of EBVaGC.