scholarly journals A Tumor of Composite Cervical Adenocarcinoma with MUCIN Gene Mutation：A Case Report

2021 ◽  
Author(s):  
Meijun Guo ◽  
Guoping Li ◽  
Xiuxiu Jiang ◽  
Shiming Lv
Keyword(s):  
Cervical Cancer ◽  
Gene Mutations ◽  
Gene Sequencing ◽  
Enrichment Analysis ◽  
Cervical Adenocarcinoma ◽  
Cervical Lesions ◽  
Transitional Area ◽  
Mucin Gene ◽  
Gastric Type ◽  
Minimal Deviation

Abstract Background:There are reports about the coexistence of two kinds of tumors in the same patient,which is believed that this phenomenon is caused by the dedifferentiation between the two tumors.In this paper, we report an human papillomavirus (HPV) negative cervical adenocarcinoma in a patient composed of two adenocarcinoma components,which is first reported.Histologically, both minimal deviation adenocarcinoma (MDA) and poorly differentiated gastric type adenocarcinoma (GTA) components, as well as their transitional area, were observed.Methods:This case of cervical cancer was screened by gene sequencing. For detection of specific somatic mutations in MDA and GTA, we filtered out mutations in malignant cervical cancer blood sample and 7 common cervical carcinoma. Then the genes were screened and identified based on the enrichment analysis of GO and KEGG and related literature reports. Results:We found 13 specific somatic gene mutations in total. Among these genes, only Mucin gene was transformed from gene level to protein level, and was positive in both MDA and GTA components of the patient by immunohistochemistry.Both components had genes mutation of MUC4 and MUC17,the component in MDA had gene mutation of MUC3A,and we found that MUC3A and MUC17 were on the same chromosome. Moreover,MUC3A and MUC4 genes were found to be fused in FusionGDB database. Conclusion:According to the reports of MUC3A,MUC4 and MUC17 genes mutation in cervical adenocarcinoma and gene fusions in tumorigenesis, we speculate that the occurrence of the transformation of pathological type from MDA to GTA in this case of cervical cancer is related to the mechanism of MUC3A and MUC4 gene fusion.We would advice, for HPV negative or atypical cervical lesions, immunohistochemistry of MUCIN genes staining and gene sequencing should be considered, which may find unusual cancer types and change the prognosis of patients.

scholarly journals A tumor of composite cervical adenocarcinoma with MUCIN gene mutation：a case report

2021 ◽  
Author(s):  
Meijun Guo ◽  
Guoping Li ◽  
Xiuxiu Jiang ◽  
Shiming Lv
Keyword(s):  
Cervical Cancer ◽  
Gene Mutations ◽  
Gene Sequencing ◽  
Enrichment Analysis ◽  
Cervical Adenocarcinoma ◽  
Cervical Lesions ◽  
Transitional Area ◽  
Mucin Gene ◽  
Gastric Type ◽  
Minimal Deviation

Abstract Background : There are reports about the coexistence of two kinds of tumors in the same patient,which is believed that this phenomenon is caused by the dedifferentiation between the two tumors.In this paper, we report an human papillomavirus (HPV) negative cervical adenocarcinoma in a patient composed of two adenocarcinoma components,which is first reported.Histologically, both minimal deviation adenocarcinoma (MDA) and poorly differentiated gastric type adenocarcinoma (GTA) components, as well as their transitional area, were observed.Methods : This case of cervical cancer was screened by gene sequencing. For detection of specific somatic mutations in MDA and GTA, we filtered out mutations in malignant cervical cancer blood sample and 7 common cervical carcinoma. Then the genes were screened and identified based on the enrichment analysis of GO and KEGG and related literature reports. Results : We found 13 specific somatic gene mutations in total. Among these genes, only Mucin gene was transformed from gene level to protein level, and was positive in both MDA and GTA components of the patient by immunohistochemistry.Both components had genes mutation of MUC4 and MUC17,the component in MDA had gene mutation of MUC3A,and we found that MUC3A and MUC17 were on the same chromosome. Moreover,MUC3A and MUC4 genes were found to be fused in FusionGDB database. Conclusion : According to the reports of MUC3A,MUC4 and MUC17 genes mutation in cervical adenocarcinoma and gene fusions in tumorigenesis, we speculate that the occurrence of the transformation of pathological type from MDA to GTA in this case of cervical cancer is related to the mechanism of MUC3A and MUC4 gene fusion.We would advice, for HPV negative or atypical cervical lesions, immunohistochemistry of MUCIN genes staining and gene sequencing should be considered, which may find unusual cancer types and change the prognosis of patients.

scholarly journals Identification and validation of the high expression of pseudogene TCAM1P in cervical cancer via integrated bioinformatics analysis

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuanhang Zhu ◽  
Chenchen Ren ◽  
Li Yang ◽  
Zhenan Zhang ◽  
Meiyuan Gong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Gene Ontology ◽  
Dna Replication ◽  
Enrichment Analysis ◽  
Testis Cancer ◽  
High Grade ◽  
Cervical Lesions ◽  
Hpv E6 ◽  
Rip Assay

Abstract Background HPV as the main cause of cervical cancer has long been revealed, but the detailed mechanism has not yet been elucidated. The role of testis/cancer antigen in cervical cancer has been revealed. However, there are no reports about the statement of testis/cancer-specific non-coding RNA. In this study, we first proposed TCAM1P as a testis/cancer-specific pseudogene, and used a series of experimental data to verify its relationship with HPV, and analyzed its diagnosis value of high-grade cervical lesions and the mechanism of their high expression in cervical cancer. This provides a new direction for the prevention and treatment of cervical cancer. Methods The specific expression of pseudogenes in each tissue was calculated by “TAU” formula. ROC curve was used to judge the diagnosed value of TCAM1P for high-grade lesions. The proliferation ability of cells was measured by CCK8. The expression of TCAM1P, HPV E6/E7 were detected by qRT-PCR. The binding for RBPs on TCAM1P was predicted by starbase v2.0 database, then RIP assay was used to verify. Besides, Gene Ontology (GO) and KEGG enrichment analysis were performed with “clusterprofiler” R package. Results TCAM1P was specifically high-expressed in normal testicular tissue and cervical cancer. Interesting, with the severity of cervical lesions increased, the expression of TCAM1P increased, and TCAM1P could effectively diagnose high-grade cervical lesions. Besides, the expression of TCAM1P was HPV dependent, with highest expression in HPV-positive cervical cancer tissues. Furthermore, RIP assay showed that EIF4A3 regulated the expression of TCAM1P through binding with it. CCK8 assay showed that TCAM1P promoted the proliferation and the Gene ontology (GO) and KEGG Pathway enrichment analysis same suggested that TCAM1P is involved in multiple ways in cell proliferation including Cell cycle, DNA replication and etc. Conclusions In this study, we firstly proposed that TCAM1P is cancer/testis pseudogene and is regulated by HPV E6/E7 and EIF4A3. TCAM1P promotes the proliferation of cervical cancer cells and acts as promoter in cervical cancer. Otherwise, TCAM1P promote proliferation through regulating cell cycle and DNA replication, but more evidence needs to be provided to reveal the mechanism by which TCAM1P plays a role in cervical cancer.

E6 and E7 oncoproteins: Potential targets of cervical cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ramarao Malla ◽  
Mohammad Amjad Kamal
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Immune Therapy ◽  
Cervical Lesions ◽  
Diagnostic Strategies ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

: Cervical cancer (CC) is the fourth leading cancer in women in the age group 15-44 globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers the recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies could be useful for the prevention and treatment of cervical cancer.

Gastric-type cervical adenocarcinoma with squamous differentiation: buried in adenosquamous carcinomas?

2021 ◽  
Author(s):  
Hiroshi Yoshida ◽  
Tomoaki Naka ◽  
Mayumi Kobayashi-Kato ◽  
Nao Kikkawa ◽  
Yasuhito Tanase ◽  
...  
Keyword(s):  
Cervical Adenocarcinoma ◽  
Squamous Differentiation ◽  
Gastric Type

scholarly journals Immunogenomic Identification for Predicting the Prognosis of Cervical Cancer Patients

2021 ◽  
Vol 22 (5) ◽  
pp. 2442
Author(s):  
Qun Wang ◽  
Aurelia Vattai ◽  
Theresa Vilsmaier ◽  
Till Kaltofen ◽  
Alexander Steger ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Clinical Data ◽  
Regulatory Network ◽  
Univariate Analysis ◽  
Predictive Biomarkers ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Functional Enrichment ◽  
Wilcoxon Test

Cervical cancer is primarily caused by the infection of high-risk human papillomavirus (hrHPV). Moreover, tumor immune microenvironment plays a significant role in the tumorigenesis of cervical cancer. Therefore, it is necessary to comprehensively identify predictive biomarkers from immunogenomics associated with cervical cancer prognosis. The Cancer Genome Atlas (TCGA) public database has stored abundant sequencing or microarray data, and clinical data, offering a feasible and reliable approach for this study. In the present study, gene profile and clinical data were downloaded from TCGA, and the Immunology Database and Analysis Portal (ImmPort) database. Wilcoxon-test was used to compare the difference in gene expression. Univariate analysis was adopted to identify immune-related genes (IRGs) and transcription factors (TFs) correlated with survival. A prognostic prediction model was established by multivariate cox analysis. The regulatory network was constructed and visualized by correlation analysis and Cytoscape, respectively. Gene functional enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 204 differentially expressed IRGs were identified, and 22 of them were significantly associated with the survival of cervical cancer. These 22 IRGs were actively involved in the JAK-STAT pathway. A prognostic model based on 10 IRGs (APOD, TFRC, GRN, CSK, HDAC1, NFATC4, BMP6, IL17RD, IL3RA, and LEPR) performed moderately and steadily in squamous cell carcinoma (SCC) patients with FIGO stage I, regardless of the age and grade. Taken together, a risk score model consisting of 10 novel genes capable of predicting survival in SCC patients was identified. Moreover, the regulatory network of IRGs associated with survival (SIRGs) and their TFs provided potential molecular targets.

scholarly journals Raman spectroscopic study of cervical precancerous lesions and cervical cancer

2021 ◽  
Author(s):  
Jing Wang ◽  
Cheng-Xia Zheng ◽  
Cai-Ling Ma ◽  
Xiang-Xiang Zheng ◽  
Xiao-Yi Lv ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Squamous Cell Carcinoma ◽  
Raman Spectra ◽  
Precancerous Lesions ◽  
Cervical Squamous Cell Carcinoma ◽  
Cervical Lesions ◽  
Cin Iii ◽  
Cervical Precancerous Lesions ◽  
Biochemical Components ◽  
The Difference

AbstractEarly detection of cervical lesions, accurate diagnosis of cervical lesions, and timely and effective therapy can effectively avoid the occurrence of cervical cancer or improve the survival rate of patients. In this paper, the spectra of tissue sections of cervical inflammation (n = 60), CIN (cervical intraepithelial neoplasia) I (n = 30), CIN II (n = 30), CIN III (n = 30), cervical squamous cell carcinoma (n = 30), and cervical adenocarcinoma (n = 30) were collected by a confocal Raman micro-spectrometer (LabRAM HR Evolution, Horiba France SAS, Villeneuve d’Ascq, France). The Raman spectra of six kinds of cervical tissues were analyzed, the dominant Raman peaks of different kinds of tissues were summarized, and the differences in chemical composition between the six tissue samples were compared. An independent sample t test (p ≤ 0.05) was used to analyze the difference of average relative intensity of Raman spectra of six types of cervical tissues. The difference of relative intensity of Raman spectra of six kinds of tissues can reflect the difference of biochemical components in six kinds of tissues and the characteristic of biochemical components in different kinds of tissues. The classification models of cervical inflammation, CIN I, CIN II, CIN III, cervical squamous cell carcinoma, and cervical adenocarcinoma were established by using a support vector machine (SVM) algorithm. Six types of cervical tissues were classified and identified with an overall diagnostic accuracy of 85.7%. This study laid a foundation for the application of Raman spectroscopy in the clinical diagnosis of cervical precancerous lesions and cervical cancer.

scholarly journals Bioinformatics analysis of differentially expressed genes and pathways in the development of cervical cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Baojie Wu ◽  
Shuyi Xi
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Targets ◽  
Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Kegg Pathways

Abstract Background This study aimed to explore and identify key genes and signaling pathways that contribute to the progression of cervical cancer to improve prognosis. Methods Three gene expression profiles (GSE63514, GSE64217 and GSE138080) were screened and downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) were screened using the GEO2R and Venn diagram tools. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Gene set enrichment analysis (GSEA) was performed to analyze the three gene expression profiles. Moreover, a protein–protein interaction (PPI) network of the DEGs was constructed, and functional enrichment analysis was performed. On this basis, hub genes from critical PPI subnetworks were explored with Cytoscape software. The expression of these genes in tumors was verified, and survival analysis of potential prognostic genes from critical subnetworks was conducted. Functional annotation, multiple gene comparison and dimensionality reduction in candidate genes indicated the clinical significance of potential targets. Results A total of 476 DEGs were screened: 253 upregulated genes and 223 downregulated genes. DEGs were enriched in 22 biological processes, 16 cellular components and 9 molecular functions in precancerous lesions and cervical cancer. DEGs were mainly enriched in 10 KEGG pathways. Through intersection analysis and data mining, 3 key KEGG pathways and related core genes were revealed by GSEA. Moreover, a PPI network of 476 DEGs was constructed, hub genes from 12 critical subnetworks were explored, and a total of 14 potential molecular targets were obtained. Conclusions These findings promote the understanding of the molecular mechanism of and clinically related molecular targets for cervical cancer.

scholarly journals A Comprehensive Understanding of the Anticancer Mechanisms of FDY2004 Against Cervical Cancer Based on Network Pharmacology

2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110043
Author(s):  
Ho-Sung Lee ◽  
In-Hee Lee ◽  
Kyungrae Kang ◽  
Sang-In Park ◽  
Minho Jung ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Cellular Functions ◽  
Papillomavirus Infection ◽  
Pharmacological Targets ◽  
Systemic Level ◽  
Viral Carcinogenesis ◽  
Persicae Semen ◽  
Phytochemical Components

Herbal drugs are continuously being developed and used as effective therapeutics for various cancers, such as cervical cancer (CC); however, their mechanisms of action at a systemic level have not been explored fully. To study such mechanisms, we conducted a network pharmacological investigation of the anti-CC mechanisms of FDY2004, an herbal drug consisting of Moutan Radicis Cortex, Persicae Semen , and Rhei Radix et Rhizoma. We found that FDY2004 inhibited the viability of human CC cells. By performing pharmacokinetic evaluation and network analysis of the phytochemical components of FDY2004, we identified 29 bioactive components and their 116 CC-associated pharmacological targets. Gene ontology enrichment analysis showed that the modulation of cellular functions, such as apoptosis, growth, proliferation, and survival, might be mediated through the FDY2004 targets. The therapeutic targets were also key components of CC-associated oncogenic and tumor-suppressive pathways, including PI3K-Akt, human papillomavirus infection, IL-17, MAPK, TNF, focal adhesion, and viral carcinogenesis pathways. In conclusion, our data present a comprehensive insight for the mechanisms of the anti-CC properties of FDY2004.

scholarly journals Multiple ASF/SF2 Sites in the Human Papillomavirus Type 16 (HPV-16) E4-Coding Region Promote Splicing to the Most Commonly Used 3′-Splice Site on the HPV-16 Genome

2010 ◽  
Vol 84 (16) ◽  
pp. 8219-8230 ◽  
Author(s):  
Monika Somberg ◽  
Stefan Schwartz
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Splice Site ◽  
Binding Sites ◽  
Mrna Levels ◽  
Coding Region ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
E6 And E7

ABSTRACT Our results presented here demonstrate that the most abundant human papillomavirus type 16 (HPV-16) mRNAs expressing the viral oncogenes E6 and E7 are regulated by cellular ASF/SF2, itself defined as a proto-oncogene and overexpressed in cervical cancer cells. We show that the most frequently used 3′-splice site on the HPV-16 genome, site SA3358, which is used to produce primarily E4, E6, and E7 mRNAs, is regulated by ASF/SF2. Splice site SA3358 is immediately followed by 15 potential binding sites for the splicing factor ASF/SF2. Recombinant ASF/SF2 binds to the cluster of ASF/SF2 sites. Mutational inactivation of all 15 sites abolished splicing to SA3358 and redirected splicing to the downstream-located, late 3′-splice site SA5639. Overexpression of a mutant ASF/SF2 protein that lacks the RS domain, also totally inhibited the usage of SA3358 and redirected splicing to the late 3′-splice site SA5639. The 15 ASF/SF2 binding sites could be replaced by an ASF/SF2-dependent, HIV-1-derived splicing enhancer named GAR. This enhancer was also inhibited by the mutant ASF/SF2 protein that lacks the RS domain. Finally, silencer RNA (siRNA)-mediated knockdown of ASF/SF2 caused a reduction in spliced HPV-16 mRNA levels. Taken together, our results demonstrate that the major HPV-16 3′-splice site SA3358 is dependent on ASF/SF2. SA3358 is used by the most abundantly expressed HPV-16 mRNAs, including those encoding E6 and E7. High levels of ASF/SF2 may therefore be a requirement for progression to cervical cancer. This is supported by our earlier findings that ASF/SF2 is overexpressed in high-grade cervical lesions and cervical cancer.

Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for advanced cervical cancer

2017 ◽  
Vol 58 (9) ◽  
pp. 1147-1154 ◽  
Author(s):  
Yan Xu ◽  
Lijing Zhu ◽  
Tong Ru ◽  
Huanhuan Wang ◽  
Jian He ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Doppler Ultrasound ◽  
Power Doppler ◽  
Three Dimensional ◽  
Complete Response ◽  
Advanced Cervical Cancer ◽  
Power Doppler Ultrasound ◽  
Cervical Lesions ◽  
Early Assessment ◽  
Prospective Longitudinal

Background Three-dimensional power Doppler ultrasound (3D-PDU) imaging has been widely applied to the differentiation of benign and malignant cervical lesions; however, its potential value for predicting response to chemo-radiotherapy has not been fully explored. Purpose To investigate the feasibility of 3D-PDU imaging in predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancer. Material and Methods Fifty-two patients with advanced cervical cancer who received CCRT underwent 3D-PDU examinations at four timepoints: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Final tumor response was determined by change in tumor size using magnetic resonance imaging (MRI). Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome. Results Of the 52 patients, 32 patients who completed all four examinations were included in the analyses: 21 were classified as complete response (CR) and 11 as partial response (PR). During the treatment, the CR group showed that 3D vascular indices (VI and VFI) significantly increased at 1 week ( P = 0.028, P = 0.017, respectively) then decreased at 2 weeks and obviously decreased at therapy completion (both P < 0.001), whereas tumors significantly decreased in volume at 2 weeks after therapy initiation ( P < 0.05). However, no significant differences in 3D vascular indices values were seen in the PR group during the treatment course (all P > 0.05). Conclusion Prospective longitudinal 3D-PDU imaging may have potentials in monitoring early therapeutic response to CCRT in patients with cervical cancer.

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