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Objective:This study constructs networks and screens potential early-warning plasma biomarkers specific for cervical cancer in Uygur women based on the proteomic data of a previous study by using MetaCoreTM Analysis. This study also explains the canceration mechanism of cervical cancer. Methods:A total of 43 plasma differential core proteins, which were analyzed and identified by proteomic techniques, underwent enrichment analysis of protein functional annotation, biological process, cellular component, GeneGo network distribution and network construction, and biomarker assessment by using MetaCoreTM online bioinformatics software. Results:The result of the MetaCoreTM analysis shows that the negative regulation of cellular component organization, reverse cholesterol transport, and negative regulation of response to stimulus were the most frequently identified functions of the selected differential proteins. The regulation of metabolism, bile acid regulation of lipid metabolism, negative farnesoid X-activated receptor-dependent regulation of bile acid concentration, inflammation complement system, cytoskeleton actin filaments, signal transduction estrogen receptor 1 membrane pathway, and inflammation interleukin-6 signaling were identified as the canonical pathways that are overrepresented in cervical cancer. The MetaCore network of selected proteins, which was constructed using the shortest path algorithm with four plasma proteins (antithrombinⅢ(ATⅢ), clusterin (CLU), villin1 (VIL1), and immunoglobulin kappa locus (IGK@)) as candidate biomarkers, was screened. Conclusion:The proteins ATⅢ, CLU, VIL1, and IGK@can be considered candidate plasma biomarkers of cervical cancer. The mechanism of occurrence and de-velopment of cervical cancer was further explained by MetaCoreTM bioinformatics analysis, thereby enhancing the early-warning system for cervical cancer.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the relationship between human papillomavirus(HPV) infection and expression of human leukocyte antigen class I (HLA-I) family genes (HLA-A, B and C) in cervical cancers of Uighur women, and to investigate their effect on cervical cancer progression.</p><p><b>METHODS</b>Fresh tissue samples of 78 Uighur women with cervical squamous carcinoma, cervical intraepithelial neoplasia (CIN) or benign cervicitis were selected. HLA-A, B and C expression and HPV infection were analyzed using RT-PCR and HPV gene chips, respectively.</p><p><b>RESULTS</b>There was a tendency of increasing the total loss of HLA-A, B and C mRNA as the cervical lesions became more aggressive. Loss of HLA-I mRNA in CIN (I, II and III) and cervical squamous carcinoma was 70.0% (14/20) and 84.8% (39/46) respectively. Poorly differentiated cervical carcinomas had the highest HLA-I expression loss (90.6%). In contrast, HLA-I mRNA loss was seen in only 8% of cases of cervicitis. Moreover, it was found that high risk HPV 16 infection was strongly correlated with the loss HLA-I mRNA expression (r = 0.803, P < 0.01).</p><p><b>CONCLUSIONS</b>The loss of HLA-I gene expression is strongly correlated with HPV-16 infection, and may serve as a biomarker of cervical cancer progression in Uighur women.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Carcinoma, Squamous Cell , Ethnology , Genetics , Allergy and Immunology , Virology , Uterine Cervical Dysplasia , Ethnology , Genetics , Allergy and Immunology , Virology , China , Ethnology , HLA Antigens , Genetics , Metabolism , HLA-A Antigens , Genetics , Metabolism , HLA-B Antigens , Genetics , Metabolism , HLA-C Antigens , Genetics , Metabolism , Human papillomavirus 16 , Papillomavirus Infections , Ethnology , Genetics , Allergy and Immunology , Virology , RNA, Messenger , Metabolism , Uterine Cervical Neoplasms , Ethnology , Genetics , Allergy and Immunology , Virology , Uterine Cervicitis , Ethnology , Genetics , Allergy and Immunology , VirologyABSTRACT
Objective To study the expression of O6-methylguanine-DNA methyltransferase (MGMT) and its clinicopathological significance in thyroid cancer.Methods Immunohistochemistry was used to determine the expression of MGMT in 61 thyroid cancer tissues, 21 thyroid adenomas, 15 Hashimoto's thyroiditis, 8 nodular goiter, and 12 peri-tumor tissues. Results There was statistic difference in the expression of MGMT between the normal tissues and thyroid cancers (P＜0.05). Expression of MGMT increased from the normal tissue (16.67%, 10/12), nodular goiter (25.00%, 2/8), Hashimoto's thyroiditis (60.00%, 9/15), and thyroid adenoma (52.38%, 11/21)to thyroid cancer (60.66%, 38/61). Expression of MGMT in papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) had significant difference (P＜0.05), and the expression level of MGMT decreased with the malignancy of thyroid cancer, such as in PTC (72.22%, 26/36), and FTC (50.00%, 8/16). There was no statistic difference in MGMT expression in sex, age, and nationality (P＞0.05).Conclusion High expression of MGMT might be related to the malignancy of thyroid cancer, which may be one of the diagnosis indexes for thyroid cancer. It will be a common clinical index in diagnosingthyroid cancer since there is no difference in MGMT expression among sexes, ages, and nationalities.
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The present study aimed to investigate the mRNA expression levels of collagen, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) in the left and right atria in patients with chronic atrial fibrillation (CAF). Forty five patients with valvular heart disease were sampled in this study, including 18 patients with sinus rhythm (SR), 27 patients with CAF. Clinical data of these patients were collected, and the left and right atrial appendages were obtained from these patients during heart valvular replacement surgery. The mRNA levels of collagen type I, collagen type III, MMP1, MMP9, TMP1 of the atria were then measured by semi-quantitative RT-PCR. The results obtained were as follows. Compared to those in SR group, in atria of CAF group, the mRNA levels of collagen type I, MMP1 and MMP9 increased (P<0.05), while the mRNA level of TMP1 decreased (P<0.01). There were no significant differences in the mRNA levels of collagen type I, collagen type III, MMP1, MMP9 and TMP1 between the left and right atria of SR group (P>0.05). In CAF group, the mRNA level of MMP1 in the right atrium was higher than that in the left atrium (P<0.05), however, the mRNA level of MMP9 in the left atrium was higher than that in the right atrium (P<0.01). In both the left and right atria, the mRNA of collagen type I was positively correlated with the corresponding atrial diameter; the mRNA of MMP1 and MMP9 was positively correlated with the mRNA of collagen type I, and was negatively correlated with the mRNA of TMP1. These results suggest that the increased level of collagen type I associated with selective upregulation of MMP1, 9 and downregulation of TMP1, 9 in the atrium might be the molecular basis of atrial interstitial fibrosis in patients with CAF. Moreover, during CAF development, there is difference in the expression of MMPs between the left and right atria.