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.

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.

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.

scholarly journals The Origin of Tumor DNA in Urine of Urogenital Cancer Patients: Local Shedding and Transrenal Excretion

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 535
Author(s):  
Anouk E. Hentschel ◽  
Rianne van den Helder ◽  
Nienke E. van Trommel ◽  
Annina P. van Splunter ◽  
Robert A. A. van Boerdonk ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Bladder Tumor ◽  
Great Promise ◽  
Tumor Tissues ◽  
Catheter Urine ◽  
Tumor Dna ◽  
Urogenital Cancers

In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.

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 Effect of modified neoadjuvant chemotherapy on levels of E6 oncoprotein in HPV-infected cervical tumor tissue

2021 ◽  
Vol 67 (4) ◽  
pp. 531-537
Author(s):  
Elena Frantsiyants ◽  
Anna Menshenina ◽  
Tatiana Moiseenko ◽  
Natalia Ushakova ◽  
Ekaterina Verenikina ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hpv Infection ◽  
Main Group ◽  
Control Group ◽  
Cervical Tumor ◽  
E6 Oncoprotein ◽  
Tumor Tissues ◽  
Group 2 ◽  
Group 1

. Background. Human papillomavirus (HPV) has been established to be the etiological factor of cervical cancer (CC). HPV infection and CC progression involve the direct participation of the E6 oncoprotein. Aim. An analysis of the E6 oncoprotein levels in tissues of the tumor and its perifocal area in HPV-associated cervical squamous cell cancer as an objective indicator of the effect of treatment depending on preoperative chemotherapy. Material and methods. The study included clinical and laboratory data of 237 patients with high-risk HPV infection of the cervix. The patients were divided into 4 groups: two main groups (CC T2а2–2bN0–1M0) and two control groups. Patients in the main group 1 (n=84) received standard neoadjuvant chemotherapy (NACT), in the main group 2 (n=93) — modified NACT with prior plasmapheresis session and a parallel course of nonspecific immunotherapy with Allokin-alpha. Control group 1 (n=40) included patients with CC T1b2–2a1N0–1M0, surgical treatment; control group 2 (n=20) — HPV-positive patients without CC. Levels of E6 were measured in samples of the cervical tumor and perifocal tissues. Results. The lowest levels of the E6 oncoprotein were registered in the group of HPV-positive patients without CC. After modified NACT, E6 levels in tumor tissues remained 4.6 times higher than in intact tissues, and even so, these patients demonstrated minimal E6 levels compared to other CC patients. E6 in tumor tissues was significantly lower than in main group 1 (by 3.3 times) and 8 times lower than in control group 1. E6 levels in the perifocal tissues of patients in main group 2 were 1.9 times lower than in the corresponding tissues of patients in main group 1 and 2.2 times lower than in control group 1. Conclusions. Inclusion of plasmapheresis and inducers of endogenous interferonogenesis into neoadjuvant treatment for cervical cancer can be considered pathogenetically justified, since it affects the key unit of cervical carcinogenesis.

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