ABSTRACT
The mechanism underlying CD4CD25Foxp3regulatory T cells (Tregs) promoting the development of colorectal cancer (CRC) was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4CD25Foxp3Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues (P< 0.01). Pearson correlation analysis indicated that the expression level of Foxp3 was positively correlated with Stat3 at mRNA level (r=0.526, P=0.036), and was positively correlated with IL-10 at protein level (r=0.314, P=0.030). The Foxp3 expressed in CD4CD25Foxp3Tregs was correlated with the histological grade, lymph node metastasis and TNM stage of CRC (P<0.05 for all). The IL-10 expression was correlated with the histological grade and TNM stage (both P<0.05). The Stat3 expression was correlated with the lymph node metastasis and TNM stage (both P<0.05). It was concluded that CD4CD25Foxp3Tregs can inhibit tumor immunity in combination with some other related inhibitory cytokines and that Foxp3 expression in CD4CD25Foxp3Tregs correlates with CRC progression.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , CD4-Positive T-Lymphocytes , Allergy and Immunology , Colorectal Neoplasms , Genetics , Allergy and Immunology , Pathology , Forkhead Transcription Factors , Genetics , Allergy and Immunology , Gene Expression Regulation, Neoplastic , Allergy and Immunology , Immunity , Genetics , Interleukin-10 , Allergy and Immunology , Interleukin-2 Receptor alpha Subunit , Allergy and Immunology , Lymphatic Metastasis , STAT3 Transcription Factor , Allergy and Immunology , T-Lymphocytes, Regulatory , Allergy and ImmunologyABSTRACT
MicroRNAs (miRNAs) play important roles in carcinogenesis, but the global miRNA expression profile in gastric stromal tumor tissues remains unclear. This study was to examine the miRNA expression profile in gastric stromal tumor tissues and explore the function of dysregulated miRNAs by performing gene ontology (GO) and pathway enrichment analysis. Total RNA was extracted and purified from 3 pairs of frozen gastric stromal tumor tissues and the adjacent non-tumor tissues by using mirVana™ miRNA isolation kit. The miRNA expression was analyzed with Affymetrix microarrays (version 4.0) containing 2578 human mature microRNA probes. The dysregulated microRNAs were validated by quantitative RT-PCR in 30 pairs of gastric stromal tumor tissues. The target gene of the dysregulated microRNAs was predicted by miRanda, TargetScan and PicTar. GO and pathway enrichment analysis was conducted to examine the potential function of miR-3178 and miR-193a-5p. The results showed that there were 12 differently expressed microRNAs in gastric stromal tumor tissues, among which 10 miRNAs were down-regulated, and 2 were up-regulated (P<0.05). The validation results by RT-PCR were in accordance with those by microRNA microarry. GO analysis found that the target genes of miR-3178 were involved in 5 GO terms and those of miR-193a-5p in 7 GO terms in level 2. Pathway enrichment analysis suggested that miR-3178 and miR-193a-5p were related to 57 and 122 signaling pathways, respectively. It was concluded that gastric stromal tumor displays a unique miRNA signature. This specific expression may become a new diagnostic and prognostic biomarker for gastric stromal tumor. miR-3178 and miR-193a-5p function as suppressive microRNAs, and they may also become diagnosis and treatment targets for gastric stromal tumor.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Gastrointestinal Stromal Tumors , Genetics , General Surgery , Gene Expression Profiling , MicroRNAs , Genetics , Stomach Neoplasms , Genetics , General SurgeryABSTRACT
Objective To understand the association of human leukocyte antigen (HLA)-DRB polymorphism and patients diagnosed as hemorrhagic fever with renal syndrome (HFRS). Methods HLA-DR allele polymorphism was detected by PCR-sequence specific primers (PCR-SSP). Hantavirus (HV) typed as Hantaan virus (HTNV) and Seoul virus (SEOV) in patients were detected by RT-heminested PCR. Results The gene frequency of DRB1*0401-0411, *1001 and *1101-1105 in HFRS case group were 3.1%, 2.2% and 15.7% respectively. Compared with control group, it was significant higher in HFRS case group (RR=13.87, 9.72 and 2.00 respectively with Chi-square value as 10.006,6.324 and 6.472 respectively, P<0.05). When compared with HFRS case group, the gene frequency of DRB1*1501-1502, DRB4 and DRB5 in control group were 11.0%, 19.0% and 16.9% respectively, markedly lower than in patients (RR=0.45, 0.58 and 0.23 respectively. Chi-square values were 6.138, 4.583 and 21.076 respectively, P<0.05). There was no significant difference in other HLA-DR gene frequencies. Mixed infection was found in Hubei, with HTNV slightly more than SEOV. Distinct hantaviruses could coexist in either different or the same geographic or ecological zores in Hubei province. Patients with HLA-DRB1*1101-1105 alleles were 81.8%(27/33) infected by HTNV and only 18.2% infected by SEOV, which had significant difference (P<0.05). Conclusion DRB1*0401-0411,*1001 and *1101-1105 were possibly associated with increased susceptibility to HV infection. On the other hand there was an inverse correlation among HFRS, DRB1*1501-1502, DRB4 and DRB5.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the functions of promoter hypermethylation of secreted frizzled-related protein (sFRP) genes in colorectal tumorigenesis and progression.</p><p><b>METHODS</b>Three colorectal cancer cell lines, RKO, HCTll6 and SW480, were treated hy 5-aza-2'-deoxycytidine and trichostatin A for demethylation. The promoter hypermethylation and expression of sFRP genes in colorectal tumor tissue and colorectal cancer cell lines were detected hy methylation-specific PCR and reverse transcription PCR, respectively.</p><p><b>RESULTS</b>None of the normal colorectal mucosa tissues showed methylation of sFRP genes. sFRP1, 2, 4 and 5 were frequently methylated in colorectal adenocarcinoma, adenoma and aberrant crypt foci (ACF) (sFRP1 > 85%, sFRP2 > 75%, sFRP5 > 50%), the differences between any two of them were not significant (P >0.05). Methylation was more frequent in colorectal tumors than in normal mucosa and adjacent normal mucosa from patients with tumor. Hypermethylation of sFRP genes was present in three colorectal cancer cell lines. When sFRP genes were methylated, their corresponding mRNA expression was absent. After cells were treated by DAC/TSA combination, the silenced sFRP expression could be effectively re-expressed.</p><p><b>CONCLUSION</b>Hypermethylation of sFRP genes is a common early event in the evolution of colorectal tumors that occurs frequently in ACF. Methylation of sFRP1, 2 and 5 genes might serve as biomarkers for the early detection of colorectal tumors. Demethylation can effectively reverse gene expression that appears possibly to be an effective way for tumor therapy.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma , Genetics , Metabolism , Pathology , Adenoma , Genetics , Metabolism , Pathology , Azacitidine , Pharmacology , Biomarkers, Tumor , Colonic Neoplasms , Genetics , Metabolism , Pathology , Colorectal Neoplasms , Genetics , Metabolism , Pathology , DNA Methylation , DNA Modification Methylases , Eye Proteins , Genetics , Metabolism , Gene Expression Regulation, Neoplastic , Gene Silencing , HCT116 Cells , Histone Deacetylase Inhibitors , Pharmacology , Hydroxamic Acids , Pharmacology , Intercellular Signaling Peptides and Proteins , Genetics , Metabolism , Membrane Proteins , Genetics , Metabolism , RNA, Messenger , MetabolismABSTRACT
0.05).The methyla tion rates were higher in tumor tissue than those in normal and adjacent mueosa(P