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MicroRNA (miRNA) negatively regulates gene expression at the post-transcriptional level.Studies find that the abnormal expression of miR-151-5p in various human tumors may play an important role in the development of human tumors,especially in the invasion and metastasis.Further studies of miR-151-5p contribute to a more in-depth understanding of tumor invasion and metastasis,which have potential value in tumor diagnosis,treatment and prognosis.
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Cell polarity is a common feature of many different types of cells,and it is essential to the normal differentiation and function of cells. Partitioning defective 6( PAR6)gene encodes PAR6 protein, which is crucial to asymmetric cell division and polarized growth. PAR6 protein as a member of the PAR6 polarity complex,affects the synthetic of centrosome and protein recruitment to the centrosome. The abnormal number of centrosomal and the loss of cell polarity may eventually lead to the occurrence of tumor.
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Isocitrate dehydrogenases(IDHs)are considered as key enzymes in the tricarboxylic acid cycle. Recurrent mutations in the IDH1 and IDH2 genes are recently found in several human cancers. Those point mutations specifically affect IDH1 and IDH2 active site arginine residues and confer a neomorphic enzyme function of directly catalyzing α-ketoglutarate(α-KG)to R-2-hydroxyglutarate(R-2-HG). R-2-HG can com-petitively inhibits α-KG-dependent enzymes and may therefore contribute to the occurrence and development of tumor. In addition,Mutation status of IDH1 and IDH2 are closely relative to the progress and prognosis of cer-tain tumor. Thus IDH1 and IDH2 are considered to be promising biomarkers for early diagnosis and prognosis and targeted therapy.
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In recent years,the abnormal expression of microRNA-21 (miR-21) in head and neck carcinoma have been found in many studies,which may be closely related to the genesis and development of thyroid carcinoma,nasopharyngeal carcinoma,laryngocarcinoma and oral carcinoma,etc.MiR-21 may also be valuable for the clinical diagnosis,treatment and prognosis of head and neck carcinoma.
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As an important member of the adisintegrin and metalloproteinase (ADAM) superfamily,ADAM17 can mediate a variety of membrane molecular hydrolysis off,such as adhesion molecules,cytokines,growth factors,etc,and play an important role in regulating tumor cell adhesion,apoptosis,metastasis and proliferation through the EGFR-PI3K-Akt pathway,Notch signaling pathway and other signaling pathways.The research of ADAM17 targeted drugs provides a new direction for cancer therapy.
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As a member of regenerating islet-derived family,regenerating islet-derived type Ⅳ(RegⅣ)is involved in cell proliferation and differentiation. RegⅣ is closely related to the occurrence and develop-ment of tumor,tumor cell proliferation and invasion and anti-apoptosis,and it may be a potential molecular tar-get of targeting therapy in cancer.
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<p><b>OBJECTIVE</b>To examine the micro-RNA (mirna) expression profile in tissues of early gastric cancer and to screen the specific mirna associated with gastric cancer.</p><p><b>METHODS</b>Gene chip technology was used to detect the expression of mirna in early gastric cancer tissues and adjacent normal tissues.</p><p><b>RESULTS</b>Compared to adjacent normal tissues, a total of 36 mirnas were down-regulated, such as mir-9-1, mir-103 and mir-141, while 12 mirnas were up-regulated, such as mir-196a, mir-142-3p and mir-25, etc.</p><p><b>CONCLUSION</b>Abnormal mirna expression level in early gastric cancer tissues may be associated to the development of gastric cancer.</p>
Subject(s)
Humans , Down-Regulation , Gene Expression Regulation, Neoplastic , MicroRNAs , Genetics , Oligonucleotide Array Sequence Analysis , Stomach Neoplasms , Genetics , Up-RegulationABSTRACT
In recent years,the abnormal expressions of BRAF,Runx2,Runx3 and S100A4 genes in thyroid papillary carcinoma have been found in many studies.The abnomal expressions of those genes are closely related to the tumor invasion,lymph node metastasis,mulifocality of thyroid papillary carcinoma,which may be valuable in clinical diagnosis and treatment.
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CpG island methylator phenotype (CIMP) refers to a set of multiple gene promoter CpG island methylation phenotype which exists in tumor at the same time.Many studies show that CIMP is ubiquitous in gastric cancer,which is related to the pathogenesis,diagnosis,patient's condition,prognosis and curative effect of gastric cancer.
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Objective To detect the expressions of microRNA-126 (miR-126) and microRNA-7 (miR-7) in esophageal squamous cell carcinoma (ESCC) and to analyze their correlations with clinicopathologic features and prognosis of ESCC.Methods The expressions of miR-126 and miR-7 in 116 ESCC samples and matched normal tissue samples were detected by real-time PCR.Statistical analysis was used to find the relationships among the expressions of miR-126 and miR-7,pathological characteristics and prognosis.Results Low expression,normal expression and high expression of miR-126 were found in 73 (62.9％),35 (30.2％) and 8 (6.9％) carcinoma samples respectively.Low expression,normal expression and high expression of miR-7 were found in 52 (44.8％),35 (30.2％) and 29 (25.0％) carcinoma samples respectively.The disease-free survival in patients with low expression of miR-126 and miR-7 was shorter than that in patients with non-low expression (x2 =4.268,P ＜0.05 ; x2 =4.993,P ＜0.05).The low expression of miR-126 was correlated with tumor location,family history and drinking (x2 =14.564,P ＜ 0.05 ; x2 =5.691,P ＜ 0.05 ; x2 =4.971,P ＜ 0.05),but was uncorrelated with gender,age,diferentiation,infiltration,lymphatic metastasis and smoking (all P ＞ 0.05).The low expression of miR-7 was uncorrelated with pathological characteristics of ESCC (all P ＞ 0.05).Conclusion The low expressions of miR-126 and miR-7 may be related to the prognosis of patients with ESCC,and have a certain clinical detection significance.
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Background and purpose:It was reported that many microRNAs (miRNAs) have close relation with carcinomas. miR-31 (microRNA-31) shows abnormal change in numerous cancers. China is one of the most high-risk areas of esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the expression of miR-31 in ESCC, and analyze the relationship of its expression with clinicopathological features and prognosis. Methods:The expression of miR-31 in KYSE410, EC1 and EC9706 cell lines, as well as 81 cases of ESCC tissues and adjacent normal esophageal tissues were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). The result was combined with clinical and follow-up data and statistical analysis was conducted. Results: MiR-31 was up-expression in 3 cell lines and 75.31% of the ESCC tissues. miR-31 up-expression was positively related to severer lymph node metastasis (P=0.043), deeper invasion of tumors (P=0.002) and advanced pathological stage (P=0.027). There was no relationship of miR-31 with other clinicopathological features (P>0.05). Furthermore, high expression of miR-31 was associated with poor progression-free survival (PFS) in 81 ESCC patients by Kaplan-Meier analysis (P=0.014) and by multivariate Cox analysis (P=0.021). Conclusion:Our results identiifed miR-31 may be a new diagnostic criteria and prognostic biomarker for ESCC.
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Recently,many studies find that microRNA plays a key role in the development,diagnosis,treatment and prevention of gastric cancer.It is confirmed that miR-451 can be used as a useful biomarker for the screening of gastric cancer.Studies also show that miR-203 and miR-21 may become diagnostic markers of gastric cancer.MicroRNA can play the role of oncogenes,and also can play the role of tumor suppressor gene,such as miR-141 plays the role of tumor suppressor gene through inhibition of the positive fibroblast growth factor receptor 2 gene expression.
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Lycopene is an important natural carotenoid,and is widely found in human tissues and blood,with the prevention of many types of cancer,anti-aging effect.It can inhibit the proliferation of cancer cells of oral malignancy,and increasing of gap-junction communication between cells to prevent oral cancer,and also can inhibit the development of colorectal cancer by reducing the activity of matrix metalloproteinase.It plays the role of anti-metastasis through enhancing the expression of anti-metastatic gene nm23-H1.
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Abnormal methylation of the tumor-related genes is frequently found in the development of gastric cancer.Cancer cells exhibit two opposing methylation abnormalities:genome-wide hypomethylation and certain tumor suppressor gene hypermethylation.Furthermore,it seems that the level of DNA methylation is closely associated with the prognosis of gastric cancer.Recently,a great deal of research has been conducted to reveal the corelation of DNA methylation and gastric cancer.
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With depth understanding of the mechanism of human leukocyte antigen G (HLA-G) protein,more and more studies have found that HLA-G is closely related with tumor immune escape.Numerous studies have shown that the expression of HLA-G protein and mRNA could be detected in patients with cancer.
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The studies have shown that the genesis and development process of breast cancer is closely related with microRNAs (miRNAs).Multiple miRNAs are involved in the progress of the incidence of breast cancer,and can be used to assess the prognosis,clinical treatment of breast cancer,and to explore the resistance mechanisms.
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ObjectiveTo investigate the methylation status of multiple genes in plasma and tumor tissues and its application in molecular diagnosis of esophageal squamous cell carcinoma (ESCC).Methods Methylation specific polymerase chain reaction (MSP) was used to detect methylation status of 5 tumor suppressor genes,such as adenomatous polyposis coli ( APC ),retinoic acid receptor-beta2 ( RARβ2 ),E-cadherin (CDH1),cyclin-dependent kinase inhibitor4A (p16INK4α) and ras association domain family member 1 A (RASSF1A) in tumour tissues,adjacent normal tissues and plasma which obtained 1 d preoperative and 7 d postoperative in 76 cases with ESCC.60 healthy volunteers were randomly selected as a control which were age-matched and sex-matched.Chi square test was used to analyze DNA methylation rates of 5 genes in various groups of tissue and plasma samples; Kappa test was used to compare the consistency of DNA methylation in the plasma samples and tissue samples,and their correlation was analyzed by Spearman correlation test; Receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity for single gene detection and 5 genes joint detection for diagnosis of esophageal squamous cell carcinoma.ResultsThe methylation rates of APC,RARβ2,CDH1,p16INK4α and RASSF1A in tumour tissues of patients with ESCC were 44.7％ ( 34/76),72.4％ ( 55/76 ),72.4％ (55/76),86.8％ ( 66/76 ),55.3％ (42/76),respectively,which were significantly higher than that in the corresponding adjacent normal tissues [ 6.6％ ( 5/76 ),3.9％ ( 3/76 ),3.9％ ( 3/76 ),3.9％ ( 3/76 ),2.6％ ( 2/76 ),x2 =29.01,75.39,75.39,105.34,57.18,all P ＜ 0.001 ].The methylation rates of above 5 genes in patients' plasma were 42.1％ ( 32/76 ),63.2％ ( 48/76 ),63.2％ ( 48/76 ),71.1％ ( 54/76 ),50.0％ ( 38/76 ),respectively,which were significantly higher than that of control group [3.3％ (2/60),3.3％ (2/60),1.7％ ( 1/60),3.3％ (2/60),1.7％ (1/60),x2 =26.88,51.62,55.01,63.48,38.30,all P ＜ 0.001 ].The methylation consistency was favorable or well between plasma and tumour tissues in patients with ESCC ( Kappa value was 0.679,0.791,0.791,0.542 and 0.895,respectively.all P ＜0.001 ).In single-gene detection for patients' plasma,methylation,the sensitivity of 5 genes was 42.1％ ( 32/76 ),63.2％ ( 48/76 ),63.2％ ( 48/76 ),71.1％ ( 54/76 ),50.0％ ( 38/76 ),respectively.The specificity was 96.7％ ( 58/60 ),96.7％ ( 58/60 ),98.3％ (59/60),96.7％ (58/60),98.3％ (59/60),respectively.The area under curve (AUC) of ROC was 0.694 [95％ confidence interval( CI)0.606 - 0.782 ) ],0.799 ( 95％ CI 0.723 - 0.875 ),0.807 ( 95％CI 0.733 - 0.882),0.839 ( 95 ％ CI 0.769 - 0.908 ) and 0.742 ( 95 ％ CI 0.659 - 0.824 ),respectively.In united testing of 5 genes,the sensitivity was 80.3％ and the specificity was 88.3％,AUC was 0.843 (95％CI 0.773 -0.913 ).The sensitivity of united testing was significantly higher than that of single-gene detection of APC and RASSF1A(x2 =23.30,15.33 ; P ＜ 0.001 ),except RARβ2,CDH1 and p16INK4α (x2 =5.48,5.48,1.75; P =0.019,0.019,0.186);There was no significant differences in specificity between united testing and single-gene detection (x2 =1.922,1.922,3.348,1.922,3.348,all P ＞ 0.05 ).Conclusions The methylation consistency is favorable or well between tumour tissues and plasma in patients with ESCC.There is no significant superior in diagnosing ESCC with united testing of multiple tumor suppressor genes methylation in plasma than with single-gene detection.But the sensitivity of the former is better than the latter.
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In recent years,a large number of researches show that the tumor related gene promoter hypermethylation is an important reason of esophageal adenocarcinoma and closely associated with the differentiation,invasion,metastasis,staging and prognosis of tumors.It might be used as a neww target for the clinical detection and therapy of esophageal adenocarcinoma.
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Variants of gene loci on susceptibility genes are the major individual susceptibility factors of esophageal squamous cell carcinoma (ESCC) in China.Some of the gene loci participate in the DNA damage and repair,and some are related with cancer suppressor genes,metabolism enzymes,trace elements and smoking.The single nucleotide polymorphisms of these susceptibility genes are closely correlated with the genesis of ESCC.
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hMSH6 is one of the most important members in the mismatch repair family. Its polymorphism is closely related to the pathogenesis and development of neoplasm, particularly in colorectal cancer and endometrial cancer. Moreover, it has been suggested to play a more important role in endometrial cancer compared with hMLH1 and hMSH2.