scholarly journals Urine miRNA Signature as a Potential Non-invasive Diagnostic and Prognostic Biomarker in Cervical Cancer

2020 ◽  
Author(s):  
Mehreen Aftab ◽  
Satish Poojari ◽  
Vaishnavi Seshan ◽  
Sachin Kumar ◽  
Pallavi Agarwal ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Hpv Infection ◽  
Clinicopathological Parameters ◽  
Non Invasive ◽  
Diagnosis And Prognosis ◽  
Cervical Precancer ◽  
Tissue Specimens ◽  
Tumor Suppressor Mirnas ◽  
Normal Controls

Abstract MicroRNAs as cancer biomarkers in serum, plasma and other body fluids are often used but analysis of miRNA in urine is limited. We investigated the expression of selected miRNAs in the paired urine, serum, cervical scrape and tumor tissue specimens from the women with cervical precancer and cancer with a view to identify if urine miRNAs could be used as reliable non-invasive biomarkers for an early diagnosis and prognosis of cervical cancer. Expression of three oncomiRs (miR-21, miR-199a, and miR-155-5p) and three tumor suppressors (miR-34a, miR-145, and miR-218) in cervical pre-cancer, cancer and normal controls including cervical cancer cell lines were analyzed using qRT-PCR. The expression of miRNAs was correlated with various clinicopathological parameters, including HPV infection and survival outcome. We observed a significant overexpression of the oncomiRs and the downregulation of tumor suppressor miRNAs. A combination of miR-145-5p, miR-218-5p, and miR-34a-5p in urine yielded 100% sensitivity and 92.8% specificity in distinguishing precancer and cancer patients from healthy controls. The expression of miR-34a-5p and miR-218-5p were found to be independent prognostic factors for overall survival of cervical cancer patients. We conclude that the evaluation of specific miRNA expression in non-invasive urine samples may serve as reliable biomarker for early detection and prognosis of cervical cancer.

scholarly journals Urine miRNA signature as a potential non-invasive diagnostic and prognostic biomarker in cervical cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mehreen Aftab ◽  
Satish S. Poojary ◽  
Vaishnavi Seshan ◽  
Sachin Kumar ◽  
Pallavi Agarwal ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Hpv Infection ◽  
Clinicopathological Parameters ◽  
Non Invasive ◽  
Diagnosis And Prognosis ◽  
Tumor Tissues ◽  
Cervical Precancer ◽  
Tissue Specimens ◽  
Normal Controls

AbstractMicroRNAs as cancer biomarkers in serum, plasma, and other body fluids are often used but analysis of miRNA in urine is limited. We investigated the expression of selected miRNAs in the paired urine, serum, cervical scrape, and tumor tissue specimens from the women with cervical precancer and cancer with a view to identify if urine miRNAs could be used as reliable non-invasive biomarkers for an early diagnosis and prognosis of cervical cancer. Expression of three oncomiRs (miR-21, miR-199a, and miR-155-5p) and three tumor suppressors (miR-34a, miR-145, and miR-218) as selected by database search in cervical pre-cancer, cancer, and normal controls including cervical cancer cell lines were analyzed using qRT-PCR. The expression of miRNAs was correlated with various clinicopathological parameters, including HPV infection and survival outcome. We observed a significant overexpression of the oncomiRs and the downregulation of tumor suppressor miRNAs. A combination of miR-145-5p, miR-218-5p, and miR-34a-5p in urine yielded 100% sensitivity and 92.8% specificity in distinguishing precancer and cancer patients from healthy controls and it well correlates with those of serum and tumor tissues. The expression of miR-34a-5p and miR-218-5p were found to be independent prognostic factors for the overall survival of cervical cancer patients. We conclude that the evaluation of the above specific miRNA expression in non-invasive urine samples may serve as a reliable biomarker for early detection and prognosis of cervical cancer.

Comprehensive Identification of the Human Secretome as Potential Indicators in Treatment Outcome of HPV-Positive and -Negative Cervical Cancer Patients

2020 ◽  
Vol 85 (5) ◽  
pp. 405-415
Author(s):  
Liang Kong ◽  
Jinjuan Wang ◽  
Jiumei Cheng ◽  
Chunyi Zang ◽  
Fang Chen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Bioinformatic Analysis ◽  
Hpv Infection ◽  
Cancer Tissue ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Diagnosis And Prognosis

<b><i>Background:</i></b> The aim of this work was to explore the novel and promising biomarkers for the diagnosis and prognosis of cervical cancer patients. <b><i>Methods:</i></b> The secretome of primary cervical tissues was extracted and then determined by the LC-MS/MS assay. The level of screened targets was confirmed using the RT-PCR and ELISA in cervical cancer tissue samples. The median expression level of certain targets was used as a cutoff value to divide the patients into 2 groups, and then the patients were followed up. The predictive abilities of the targets on the prognosis were further studied. <b><i>Results:</i></b> LC-MS/MS, together with bioinformatic analysis, demonstrated that totally 95 targets were dysregulated in cervical cancer. Among them, ECM2, KLK6, and MASP1 were increased in cervical cancer in a stage-dependent manner, whereas FGA was negatively associated with the stage of cervical cancers. Overall survival (OS) and disease-free survival (DFS) rates were significantly decreased in the KLK6 high group, whereas little difference was found between the high and low groups of other 3 cases. Univariate analysis of the 5-year OS and DFS revealed a significantly worse outcome for patients with KLK6 high tumors. In multivariate analysis, KLK6 remained a highly significant prognostic marker for OS and DFS. Combined survival analysis of KLK6 expression and the HPV infection revealed that KLK6<sup>high</sup>HPV<sup>(−)</sup> predicted the most poor OS rate and the KLK6<sup>low</sup>HPV<sup>(+)</sup> group showed the best prognosis. <b><i>Conclusion:</i></b> Through the secretome analysis, we identified a series of secreted proteins differentially expressed in the clinical cancer, among which KLK6 has the potential to become a promising biomarker for the diagnosis and prognosis of cervical cancer patients.

An MRI-based radiomics signature and clinical characteristics for survival prediction in early-stage cervical cancer

2021 ◽  
Author(s):  
Ru-ru Zheng ◽  
Meng-ting Cai ◽  
Li Lan ◽  
Xiao Wan Huang ◽  
Yun Jun Yang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Clinical Characteristics ◽  
Early Stage ◽  
Disease Free Survival ◽  
Clinicopathological Parameters ◽  
Rank Test ◽  
Survival Prediction ◽  
Early Stage Cervical Cancer ◽  
Radiomics Signature

Objectives: To investigate the prognostic role of Magnetic Resonance Imaging (MRI) based radiomics signature and clinical characteristics for overall survival (OS) and disease-free survival (DFS) in the early-stage cervical cancer. Methods: A total of 207 cervical cancer patients (training cohort: n = 144; validation cohort: n = 63) were enrolled. 792 radiomics features were extracted from T2-weighted (T2W) and diffusion weighted imaging (DWI). 19 clinicopathological parameters were collected from the electronic medical record system. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to select significant features to construct prognostic model for OS and DFS. Kaplan-Meier (KM) analysis and log-rank test were applied to identify the association between the radiomics score (Rad-score) and survival time. Nomogram discrimination and calibration were evaluated as well. Associations between radiomics features and clinical parameters were investigated by heatmaps. Results: A radiomics signature derived from joint T2W and DWI images showed better prognostic performance than that from either T2W or DWI image alone. Higher Rad-score was associated with worse OS (p < 0.05) and DFS (p < 0.05) in the training and validation set. The joint models outperformed both radiomics model and clinicopathological model alone for 3 year OS and DFS estimation. The calibration curves reached an agreement. Heatmap analysis demonstrated significant associations between radiomics features and clinical characteristics. Conclusions: The MRI-based radiomics nomogram showed a good performance on survival prediction for the OS and DFS in the early-stage cervical cancer. The prediction of the prognostic models could be improved by combining with clinical characteristics, suggesting its potential for clinical application. Advances in knowledge: This is the first study to build the radiomics-derived models based on T2W and DWI images for the prediction of survival outcomes on the early stage cervical cancer patients, and further construct a combined risk scoring system incorporating the clinical features.

scholarly journals Role of Regulatory B Cells in the Progression of Cervical Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Zhifang Chen ◽  
Yuejie Zhu ◽  
Rong Du ◽  
Nannan Pang ◽  
Fengbo Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Intraepithelial Neoplasia ◽  
Serum Levels ◽  
Hpv Infection ◽  
Control Group ◽  
Cell Percentage

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P<0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P<0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r=0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P<0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r=‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P<0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.

Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis.

1997 ◽  
Vol 15 (3) ◽  
pp. 1008-1012 ◽  
Author(s):  
C C Pao ◽  
J J Hor ◽  
F P Yang ◽  
C Y Lin ◽  
C J Tseng
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Cervical Cancer Cells ◽  
Stage Ivb ◽  
Blood Specimens ◽  
Transforming Gene ◽  
Normal Controls ◽  
Specific Mrna

PURPOSE To determine the presence of cervical cancer cells in circulating peripheral blood of stage IVb cervical cancer patients with metastasis to distant organs. PATIENTS AND METHODS Cervical cancer tissue from 15 stage IVb cervical cancer patients with metastasis were analyzed for the presence of human papillomavirus (HPV) type 16 DNA by nested polymerase chain reaction (PCR). The presence of transcriptional products of the HPV type 16 E6-transforming gene in the peripheral blood of the same 15 cancer patients was analyzed by reverse transcription and PCR. Cervical tissues and peripheral-blood specimens from 12 normal healthy individuals served as controls. RESULTS Thirteen of 15 (86.7%) cervical cancer tissues from same number of patients were found to contain HPV type 16 DNA. Peripheral-blood specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were found to contain HPV-specific mRNA detectable by reverse transcription (RT) and PCR. Cervical tissues from all 12 normal controls were HPV-free. None of the peripheral-blood specimens from two cervical HPV-negative cancer patients and 12 normal controls contained detectable amounts of mRNA of HPV type 16 E6-transforming gene. CONCLUSION The most likely source of the HPV-specific mRNA detected in the peripheral blood of cervical cancer patients with metastasis is the cervical cancer cells derived from or shed from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a sensitive indicator of circulating cervical cancer cells. If PCR positivity is proven to be able to predict disease progression reliably, these findings may have clinical applications in the treatment of cervical and many other cancers.

scholarly journals Analysis of mutations in the E6/E7 oncogenes and L1 gene of human papillomavirus 16 cervical cancer isolates from China

2006 ◽  
Vol 87 (5) ◽  
pp. 1181-1188 ◽  
Author(s):  
Yuping Wu ◽  
Yulong Chen ◽  
Longyu Li ◽  
Guifang Yu ◽  
Ying He ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Patients ◽  
Hpv Infection ◽  
Typing Method ◽  
Hpv16 E6 ◽  
Human Papillomavirus 16 ◽  
Human Papillomavirus Type 16 ◽  
New Variant

Human papillomavirus type 16 (HPV16) has a number of intratypic variants; each has a different geographical distribution and some are associated with enhanced oncogenic potential. Cervical samples were collected from 223 cervical cancer patients and from 196 age-matched control subjects in China. DNA samples were amplified by using primers specific for the E6, E7 and partial L1 regions. Products were sequenced and analysed. It was found by using a PCR–sequence-based typing method that HPV infection rates in China were 92·8 % in cervical cancer patients and 15·8 % in healthy controls. HPV16 was detected in 70·4 % of cervical cancer patients and in 6·1 % of controls. In HPV16-positive cervical cancers, 23·6 % belonged to the prototype, 65·5 % were of the Asian variant, 5·5 % were of African type 1 and 3·6 % were European variants, whilst only one was a new variant that differed from any variant published so far. Prevalences of HPV16 E6 D25E and E113D variants were 67·3 and 9 %, respectively. In addition to D25E and E113D, the following E6 variations were found in this study: R129K, E89Q, S138C, H78Y, L83V and F69L. The results also showed that the prevalences of three hot spots of E7 nucleotide variation, N29S, S63F and a silent variation, nt T846C, were 70·2 % (33/47), 51·1 % (24/47) and 61·7 % (29/47), respectively. The following L1 variations were found in this study: S377A, K387E, E378D, K382E and T379P. It was also found that the average age of Asian variant-positive cervical cancer patients (42·98±10·43 years) was 7·56 years lower than that of prototype-positive patients (50·54±10·91). It is suggested that the high frequency of HPV16 Asian variants might contribute to the high incidence of cervical cancer in China.

scholarly journals Integrin-β6 Serves as a Potential Prognostic Serum Biomarker for Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Zequn Li ◽  
Yuqi Sun ◽  
Jianfei Xu ◽  
Hao Yang ◽  
Xiaodong Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Risk Stratification ◽  
Cancer Patients ◽  
Tumor Stage ◽  
Serum Biomarker ◽  
Clinicopathological Parameters ◽  
Novel Biomarkers ◽  
Prognostic Prediction ◽  
Tissue Specimens ◽  
Gastric Cancer Patients

Discovering novel biomarkers that easily accessed is a key step towards the personalized medicine approach for gastric cancer patients. Integrin-β6 (ITGB6) is a subtype of integrin that is exclusively expressed on the surface of epithelial cells and is up-regulated in various tumors. In the present study, a retrospective cohort with 135 gastric cancer patients and a prospective cohort with 34 gastric cancer patients were constructed, ITGB6 expression were detected in both the serum specimens and the tissue specimens. Detailed clinicopathological parameters as well as patients’ survival were recorded. A nomogram including ITGB6 expression was also constructed and validated to predict the prognosis of gastric cancer patients. Results showed that serum ITGB6 expression was obviously increased and associated with tumor stage in gastric cancer patients, serum ITGB6 expression was relatively high in patients with liver metastasis. High ITGB6 expression indicated a poor prognosis, and nomogram including serum ITGB6 expression could predict the prognosis of gastric cancer patients effectively. Moreover, serum ITGB6 expression was associated with ITGB6 expression in tumor tissues. Furthermore, combined serum ITGB6 and CEA levels contributed to the risk stratification and prognostic prediction for gastric cancer patients. In addition, the serum expression of ITGB6 decreased significantly after radical surgery, and a new rise in serum ITGB6 expression indicated tumor recurrence or progression. The present study identified a novel serum biomarker for the risk stratification, prognostic prediction and surveillance of gastric cancer patients.

scholarly journals Dynamic evolution of cervical cancer mutations during chemoradiation using novel sampling approach

2019 ◽  
Author(s):  
Bhavana V. Chapman ◽  
Tatiana Karpinets ◽  
Travis T. Sims ◽  
Greyson Biegert ◽  
Xiaogang Wu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cyclin D1 ◽  
Exome Sequencing ◽  
Cancer Patients ◽  
Whole Exome Sequencing ◽  
Radiation Resistance ◽  
Radiation Treatment ◽  
The Cancer Genome Atlas ◽  
Non Invasive ◽  
Whole Exome

AbstractObjectiveThe aim of this study was to validate a whole exome sequencing approach to longitudinally characterize the tumor mutational profile of cervical cancer patients undergoing chemoradiation (CRT).Experimental DesignCervical cancer tumor specimens from twenty-seven patients undergoing chemoradiation were collected before and throughout CRT and whole exome sequencing (WES) was performed to characterize individual mutations and alterations in unique genes. WES data were analyzed from cervical cancer patients in The Cancer Genome Atlas (TCGA) as a comparison group.ResultsOver 93% of mutated genes detected at baseline were present in TCGA. Tumor purity from collected swabs correlated with MRI tumor volumes during the course of treatment (R2=0.969). CDK4/CDK6/cyclin D1-related gene mutations involved in the ERK1/2, p16INK4, and p53 pathway and G1/S checkpoint most commonly persisted at the end of CRT.ConclusionThis non-invasive swab technique to serially sample tumor during CRT will allow new discoveries of dynamic tumor mutational profile changes during chemoradiation for mucosal tumors. Mutations that survived or increased during the initial weeks of radiation treatment are potential drivers of radiation resistance including the CDL4/CDK6/cyclin D1-related pathway.Statement of Translational RelevanceThere are no established biomarkers to predict chemoradiation (CRT) response for cervical cancer patients. Serial biopsies cannot be performed due to risks of bleeding and fistula. We used a novel non-invasive swab-based biopsy technique to obtain serial samples from a cohort of twenty-seven patients through the course of treatment, and validated this approach to obtain whole exome sequencing data. We analyzed dynamic tumor mutation profiles during CRT. Results from this study show that mutations in CDK4/CDK6/cyclin D1-related genes increased at the end of CRT, suggesting this pathway as a potential driver of radiation resistance.

scholarly journals Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Feng Yang-chun ◽  
Wang Sen-yu ◽  
Zhang Yuan ◽  
Huang Yan-chun
Keyword(s):  
Cervical Cancer ◽  
Host Cell ◽  
Cancer Cells ◽  
Human Genome ◽  
Cancer Patients ◽  
High Frequency ◽  
Hpv Infection ◽  
Actual Observation ◽  
Gene Integration ◽  
Cell Genome

Background. The Uygur is the fifth most populous ethnic group in China. Compared to other Chinese population, cervical cancer in them had high incidence, and HPV infection also was particular. Their HPV integration situation has never been reported. We aimed to investigate the integration situation of 20 subtypes of HPV gene into host cell genome in Chinese Uygur cervical cancer patients; meanwhile, we explored the influence of gene integration on PD-L1 expression. Methods. 40 frozen Chinese Uygur cervical cancer specimens with positive HPV infection were obtained from the cancer prevention and treatment institute of Tumor Hospital Affiliated to Xinjiang Medical University. The integration situation of HPV gene into host cell genome was detected by Agilent SureSelect™ Target Enrichment Chip and Next-Generation Sequencing. The related genes were analyzed by GO functional annotation and KEGG pathway enrichment. The expression levels of PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Meanwhile, the relationship between PD-L1 levels in cancer cells and gene integration were analyzed. Results. The HPV multiple infection rate by HIVID was as high as 92.5%, much higher than 35.0% by the commercial kit (P<0.05). There were 13423 integration events in 40 specimens, involving 6867 human genes. These integration events were distributed on all human chromosomes, and chromosome 19 had the excessive concentration phenomenon of integration events. There were some integration hotspots in human genome such as PPP1R37, HECW2, EMBP1, ANKRD50, SPTBN4, LINC00895, LYRM4-AS1, LINC00374, RBFOX1, CSMD1, CDH13, and KLHL4. Insertion breakpoints can be found in all gene regions of the HPV genome. The actual observation of the integration times of E1 and E6 was much higher than the expected value, while the actual observation times of E5 were much lower than the expected value. The result of GO functional analysis showed that binding molecular function and cellular process biological process were the main ways to influence the cell biological behavior of HPV gene integration. The enrichment pathway analysis of KEGG showed that pathways in cancer were the most important enrichment pathways involved in the genomic integration of HPV. The positive PD-L1 rate was 62.5%. Logistic regression analysis showed that 9p24.1 existing integration sites and the number of all gene integration were risk factors for PD-L1 expression (odds ratio 17.313 and 1.012; 95% confidence interval 1.691-177.213 and 1.001-1.023). Conclusions and Relevance. Most high-frequency sites of HPV integration in Chinese Uygur cervical cancer are related to cancer progression, and the gene integration hotspots may be potential HPV carcinogenic targets. The problem of multiple HPV infection in Chinese Uygur cervical cancer patients should be paid attention. L1 and E6 genes are inapposite as the target gene of commercial HPV type detection kit, because of high-frequency breakpoints in these genes. The gene integration especially the integration existing on 9p24.1 could affect the expression level of PD-L1.

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