scholarly journals The ratio of serum Angiopoietin-1 to Angiopoietin-2 in patients with cervical cancer is a valuable diagnostic and prognostic biomarker

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3387 ◽  
Author(s):  
Ping Yang ◽  
Na Chen ◽  
Dongyun Yang ◽  
Janet Crane ◽  
Shouhua Yang ◽  
...  

Objectives Angiopoietins have been found to play essential roles in tumor angiogenesis. The present study was aimed at investigating the diagnostic and prognostic values of serum angiopoietin 1 and 2 (sAng-1 and sAng-2) in cervical cancer. Methods The sAng-1 and sAng-2 concentrations were analyzed in 77 women with cervical cancer, 44 women with cervical intraepithelial neoplasia (CIN) and 43 women without cervical lesions by enzyme-linked immunosorbent assay. The diagnostic values of sAng-1, sAng-2 and sAng-1/sAng-2 were evaluated by receiver operating characteristic (ROC) curves. The Ang-1 and Ang-2 expression in cervical cancer tissues as well as microvessel density (MVD), were assessed by immunohistochemistry. Results The concentration of sAng-2 gradually increased and the sAng-1/Ang-2 ratio was gradually decreased from normal control to CIN, then to squamous cell cancer, and the sAng-1/sAng-2 ratio was also significantly decreased in adenocarcinoma. The area under ROC curves of sAng-2 and sAng-1/sAng-2 ratio for discriminating cervical cancer from normal were 0.744 and 0.705, respectively. Decreased sAng-1/sAng-2 was significantly associated with advanced tumor stage, poor differentiation, lymph-vascular space invasion and high MVD. sAng-2 was positively correlated with the Ang-2 expression in cervix epithelia. A high sAng-1/sAng-2 ratio was associated with a longer progression-free survival and a longer overall survival in cervical cancer patients. Conclusions These findings suggest that sAng-2 and the sAng-1/sAng-2 ratio may be valuable diagnostic and prognostic biomarkers for cervical cancer.

2021 ◽  
Vol 27 ◽  
Author(s):  
Rui Bai ◽  
Bowen Diao ◽  
Kaili Li ◽  
Xiaohan Xu ◽  
Ping Yang

Objective: To investigate whether serum Tie-1 (sTie-1) is a valuable marker for predicting progression and prognosis of cervical cancer.Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sTie-1 concentrations in 75 cervical cancer patients, 40 cervical intraepithelial neoplasia (CIN) patients, and 55 healthy controls without cervical lesions, and sTie-1 levels were compared between the groups. Receiver operating characteristic curves was used to evaluate the diagnostic value of sTie-1. The relationship between sTie-1 concentrations in patients with cervical cancer and clinicopathological features and prognosis were analyzed, and the risk factors for postoperative recurrence were determined using univariate and multivariable Cox proportional hazards regression.Results: We found that sTie-1 concentrations gradually increased according to lesion severity (i.e., cancer vs. CIN; p < 0.05) and were significantly elevated in adenocarcinoma compared with healthy controls. sTie-1 levels strongly distinguished between cervical cancer patients and the healthy controls (area under the curve = 0.846; cut-off value = 1,882.64 pg/ml; sensitivity = 74.6%; specificity = 96.4%). Moreover, sTie-1 levels in cervical cancer patients were significantly associated with tumor size, advanced tumor stage, lymph node metastasis, and reduced 4-years progression-free survival. Cervical cancer patients with high sTie-1 concentrations had a 3.123-fold [95% confidence interval (CI): 1.087–8.971, p = 0.034] higher risk for tumor recurrence.Conclusions: Elevated sTie-1 levels in patients with cervical carcinoma were associated with tumor progression and poor prognosis, indicating that sTie-1 may be a valuable marker for predicting progression and prognosis of cervical cancer.


2020 ◽  
Vol 14 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Qiuling Ma ◽  
Yong Shao ◽  
Wei Chen ◽  
Cheng Quan ◽  
Yanhui Zhu ◽  
...  

Aim: To investigate whether cervical cancer (CC) and cervical intraepithelial neoplasia (CIN) can be screened by analyzing gene expression profiling of peripheral blood. Methods: RNA-sequencing analysis of blood was performed on 11 CC patients, 21 CIN patients and 19 healthy controls (H). Fifty-nine genes were validated by quantitative real-time PCR using blood samples from 46 H, 83 CC and 32 CIN patients. Results: There were significant differences in the expression levels of six genes between CC and H, five genes between CIN and H and four genes between CC and CIN (p < 0.05). Four genes discriminated cervical lesions from H with a sensitivity of 82.61%, a specificity of 87.83% and an area under the curve of 0.8981. Three genes discriminated CC from CIN with a sensitivity of 53.13%, a specificity of 96.39% and an area under the curve of 0.7786. Conclusion: Our findings provided a promising noninvasive quantitative real-time PCR diagnostic assay of CC and CIN.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Arsenio A. Spinillo ◽  
Mattia M. Dominoni ◽  
Anna A. C. Boschi ◽  
Cecilia C. Sosso ◽  
Giacomo G. Fiandrino ◽  
...  

The aim is to evaluate the clinical consequences of coinfection between HPV 16 and other high-risk HPVs among women with a histological diagnosis of CIN or invasive cervical cancer. A total of 2985 women, with a diagnosis of either CIN or cancer (<IB) on cervical or cone biopsy, were included. HPV genotypes were identified using the INNO-LiPA HPV genotyping assay, version EXTRA, on cervical scraping, before the colposcopic evaluation and the colposcopic biopsies or conization. In the overall population, HPV16 interacted positively with HPV18 (RR = 2, 95% CI 1.5–2.6) and negatively with HPV33, 51, 52, and 66, in log-linear analysis. There was an excess of CIN3 diagnoses among subjects coinfected with HPV16 and HPV18 or HPV52, although the absolute number of cases was relatively small. In a logistic model, the odds ratio of CIN3+ associated with coinfection of HPV16 and HPV18 (OR = 3.8, 95% CI 2.5–5.7, p = 0.004 compared to single HPV16) or HPV52 (OR = 3.6, 95% CI 2.6–5.1, p = 0.009 compared to single HPV) was higher than that associated with single HPV 16 infections. Finally, multiple infections had no effect on residual disease and did not influence the recurrence of high-grade CIN during a median follow-up of 25 months (IR 17–41). HPV16 interacted positively with HPV18 and negatively with HPV33, 51, 52, and 66 supporting the notion that HPV16 interacts mostly negatively with other HR-HPVs in CIN lesions. Among specimens coinfected with HPV16 and 18 or 52, there was an excess of CIN3+ although the impact on the prevalence of severe cervical lesions was limited.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17000-e17000
Author(s):  
Heming Lu ◽  
Jinming Yu ◽  
Yuying Wu ◽  
Xu Liu ◽  
Hailan Jiang ◽  
...  

e17000 Background: This study was to investigate the efficacy and safety of neoadjuvant chemoradiotherapy plus nimotuzumab followed by surgery for advanced cervical cancer. Methods: The inclusion criteria of this study were as follows: age: 18-75 years old; ECOG 0-1; FIGO stages IB2-IIIB; not eligible for surgery. IMRT with a total dose of 50-54 Gy was delivered to the tumor and the whole uterus, and 45-48.6 Gy to the high-risk regions. Weekly cisplatin or nedaplatin was administered concurrently with IMRT. Weekly nimotuzumab was given for 6 cycles. Patients were then assessed for clinical tumor response and operability. For those who were candidates for surgery, radical hysterectomy and pelvic lymph node dissection were performed 5-6 weeks after the completion of neoadjuvant therapy. Results: Twenty-eight patients were enrolled. Stage distributions were as follows: IB2, 3 pts; IIA, 5 pts; IIB, 16 pts; IIIA, 2 pts; IIIB, 2 pts. Twenty six (92.8%) patients completed ≥ 5 cycles of chemotherapy, and all completed ≥5 cycles of nimotuzumab. Complete clinical response and partial response were found in 8 patients (28.5%) and 20 patients (71.5%), respectively. Four patients were not eligible for surgery and 2 candidates refused surgery. They were not included in this analysis. Radical surgery was performed for the remaining 22 patients. Among them, 8 (36.4%) had complete pathology response, 9 (40.9%) presented with persistent atypical cells or cervical intraepithelial neoplasia, and 5 (22.7%) presented with macroscopic and/or microscopic residual disease. Median follow-up was 22 months (range, 5-39 months). The 2-year locoregional control rate, progression-free survival rate, distant metastasis-free survival rate, and overall survival rate were 95.0%, 85.2%, 84.0%, and 90.0%, respectively. Acute toxicity profiles were mainly manifested as marrow suppression, nausea, diarrhea, and loss of appetite. They were mild in general and easily manageable. Chronic toxicities were mainly limited to grade 1. No severe late toxicities were observed Conclusions: This treatment approach is highly effective and safe in advanced cervical cancer. Further studies are warranted to confirm the findings. Clinical trial information: NCT01938105.


2021 ◽  
Author(s):  
Rahima Bel Haj Rhouma ◽  
Monia Ardhaoui ◽  
Emna Fehri ◽  
Asma Marzougui ◽  
Thalja Assili ◽  
...  

Abstract BackgroundHigh-risk human papillomavirus (HR-HPV) are responsible for cervical cancer (CC), that is a major health problem worldwide and the second most prevalent gynecological cancer among Tunisian women. Preventive tools against CC are based on screening and prophylactic vaccines. Improving the preventive strategies as well as the therapeutic algorithms needs the understanding of HPV distribution in cervical lesions in Tunisian women. MethodsA total of 200 formalin-fixed paraffine embedded biopsies were collected in our study. DNA was extracted using Qiagen Mini prep kit. DNA quality was controlled by Beta Globin PCR. Only positive samples for Beta Globin test were used. HPV detection was performed by a nested PCR using PYGMY and GP5+/6+ primers. Genotyping was performed by Reverse Line hybridization using 31 probes. ResultsThe mean age of participants was 38.97 years and 54.5% were over 40 years. Cervical neoplasia distribution according to age showed that CINII/CINIII was observed in women over 30 years old. All samples were positive for Beta Globin PCR. Global HPV prevalence in cervical lesions was 83% (166/200). HPV was present in 65% in CINI, 82% in CINII/CINIII and 85% in CC. HR-HPV was statically associated with cervical intraepithelial neoplasia (p<10-3). HR-HPV distribution according to lesion grade and cervical cancer showed that HPV16 and HPV18 were present in all lesions. For CINII/CINIII, HPV 35 (33,33%) was the most detected type, followed by HPV18 (28,6%), HPV 45 (25%) and HPV 16 (21,7%). HPV 45(62%), HPV 18 (47%) were the most detected in CC. HPV58, 59, 66 were only detected in CC and associated with HPV45,18 and HPV16. HPV39, 31, 33, 52, 56, 68 and HPV70 was associated only with CINI. ConclusionsThese findings show that HR-HPV represents 54,6 % of all infections in all cervical lesions. Five HR-HPV (35, 18, 45,16, 51) were detected in CINII/CINIII with a high incidence of HPV 35, 18, 45, and 16 that are included in the proposed vaccines. These findings give useful information for vaccine implementation consideration as well as personalized decision algorithms of intra-epithelial cervical lesions in Tunisian women.


2016 ◽  
Vol 103 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Lucas G.G. de Matos ◽  
Eduardo B. Cândido ◽  
Paula V.T. Vidigal ◽  
Polyanna H.C. Bordoni ◽  
Rivia M. Lamaita ◽  
...  

Introduction The immune system plays a critical role in the defense against human papillomavirus (HPV) infection and its persistence. Toll-like receptors (TLRs) are membrane receptors responsible for activation of the innate immune response, and an association between TLR expression and uterine cervical cancer has been shown. Tumor necrosis factors (TNFs) are among the main mediators of skin and mucosa inflammation. The aim of this study was to demonstrate the association between TLR and TNF immune expression and cervical cancer and premalignant cervical lesions. Methods A total of 64 embedded tissues were obtained from gynecological procedures, including 35 specimens with cervical intraepithelial neoplasia (CIN) and 10 specimens with cervical squamous cell carcinoma (CSCC) as well as 19 normal cervical samples. The expression of TLR2, TLR3, TLR4, TNF-α and TNF-β was measured by immunohistochemistry and graded into low and high levels of expression. Results There was an association between the expression levels of TLR2 and those of TNF-α and TNF-β (p = 0.01 and p = 0.021, respectively) in the cervical cancer and CIN groups. TLR4 expression was associated with TNF-α and TNF-β expression (p = 0.016 and p = 0.025, respectively) in these 2 groups. By contrast, TLR3 was not statistically associated with TNF-α or TNF-β in any of the groups. Conclusions There might be an association of the TLR2 and TLR4 pathways with the immunological response of TNF-α and TNF-β in cervical cancer. These markers are also expressed at higher levels in cervical cancer and premalignant lesions compared to normal controls.


Author(s):  
Emilia Dąbrowska ◽  
Andrzej Przylipiak ◽  
Monika Zajkowska ◽  
Barbara Maria Piskór ◽  
Aleksandra Borowik-Zaręba ◽  
...  

The chemokine CCL5 and its receptor CCR5 play important roles in cancer invasion and metastasis. Based on our knowledge, our results were the first that presented the diagnostic usefulness of CCL5 and CCR5 in breast cancer (BC) patients, based on receiver operating characteristic (ROC) curve analysis. We wished to examine further if CCL5 and CCR5 are appropriate to be applied as BC markers for early screening. Values of tested parameters in patients’ plasma were determined by CMIA method (Chemiluminescent Microparticle Immunoassay, CA 15-3) as well as by ELISA method (Enzyme-Linked Immunosorbent Assay, CCL5 and CCR5). Levels of CCL5 in the plasma were markedly increased, while those of CCR5 were remarkably lower in BC patients when compared to the control groups. Moreover, higher levels of CCL5 in BC corresponded to advanced tumor stage, while the levels of CCR5 decreased with increasing the disease stage. CCL5 concentration was characterized by high sensitivity (SE) (68.04%) and high specificity (SP) (100.00%) in the BC patients. Results indicated that area under the curve (AUC) corresponding to CCL5 (0.8116) had a higher value than this corresponding to CA 15-3. The AUC value of CCL5 was significantly increased in the early phase of BC (stage I – 0.7089; stage II – 0.8313). The maximum range in the BC patients was observed for the combined analysis of the tested measurands with CA 15-3 (0.8335). In conclusion, our research indicates that examination of plasma CCL5 and CCR5 may be useful in BC diagnosis at the early stage of the disorder, especially when combined with CA 15-3.


2020 ◽  
Author(s):  
Yidi Liu ◽  
Huan Wu ◽  
Jingjiang Xu ◽  
Defu Chen ◽  
Hongyou Zhao ◽  
...  

Abstract Background: Cervical cancer is the fourth most common cancer in women. Early detection and diagnosis play an important role in secondary prevention of cervical cancer. This study aims to provide more information to develop an effective strategy for the prevention and control of cervical cancer in northern China. Methods: A retrospective single-centre descriptive cross-sectional study was conducted in Chinese PLA General Hospital located in Beijing, covering the period from January 2009 to June 2019. The patients who underwent a polymerase chain reaction (PCR)-based HPV genotyping test and cervical pathological diagnosis were included. Furthermore, we limited the interval between the two examination within 180 days for the purpose of making sure their correlation to analyse their relationship. Moreover, the relationship between different cervical lesions and age as well as single/multiple HPV infection was assessed.Results: A total of 3,134 patients were eligible in this study after HPV genotyping test and pathological diagnosis. Most of the patients (95%) were from northern China. Among the patients, 1,745(55.68%) had high-grade squamous intraepithelial neoplasia (HSIL), 1,354 (43.20%) had low-grade squamous intraepithelial neoplasia (LSIL) and 35 (1.12%) were Normal. The mean age was 42.06 ± 10.82(range, 17–79 years). The women aged 35-49 years accounted for the highest incidence rate. The top five most commonly identified HPV genotypes in each lesion class were as follows: HPV16, 58, 52, 31 and 51 in the class of HSIL; HPV16, 52, 58, 56 and 51 in the class of LSIL; HPV16, 31, 6,11, 52 and 58 in the class of normal. The frequencies of HPV single genotype infection and multiple genotypes infection were 55.26% and 34.18%, respectively. There was no difference in the attributable proportions of multiple genotypes infection amongst HSIL, LSIL and Normal.Conclusions: In Northern China, HPV16 was the most dominant genotype in the patients with pathological examination. The peak age of the onset of HSIL was between 35 and 49 years of age. Infection with multiple HPV genotypes did not increase the risk of HSIL. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.


2021 ◽  
Vol 28 ◽  
pp. 107327482110505
Author(s):  
Zhenzhen Liang ◽  
Lianchang Liu ◽  
Chaowei Wen ◽  
Heya Jiang ◽  
Tianxia Ye ◽  
...  

Purpose Since protein arginine methyltransferase 5 (PRMT5) is abnormally expressed in various tumors, in this study we aim to assess the association between PRMT5 and clinicopathological and prognostic features. Methods Electronic databases including PubMed, Web of Science, Scopus, ScienceDirect, and the Cochrane Library were searched until July 25, 2021. The critical appraisal of the eligible studies was performed using the Newcastle–Ottawa Quality Assessment Scale. Pooled hazard ratios (HR) and pooled odds ratios (OR) were calculated to assess the effect. Engauge Digitizer version 12.1, STATA version 15.1, and R version 4.0.5 were used to obtain and analysis the data. Results A total of 32 original studies covering 15,583 patients were included. In our data, it indicated that high level of PRMT5 was significantly correlated with advanced tumor stage (OR = 2.12, 95% CI: 1.22-3.70, P =.008; I2 = 80.7%) and positively correlated with poor overall survival (HR = 1.59, 95% CI: 1.46-1.73, P < .001; I2 = 50%) and progression-free survival (HR = 1.53, 95% CI: 1.24-1.88, P < .001; I2 = 0%). In addition, sub-group analysis showed that high level of PRMT5 was associated with poor overall survival for such 5 kinds of cancers as hepatocellular carcinoma, pancreatic cancer, breast cancer, gastric cancer, and lung cancer. Conclusion For the first time we found PRMT5 was pan-cancerous as a prognostic biomarker and high level of PRMT5 was associated with poor prognosis for certain cancers.


2021 ◽  
Vol 11 ◽  
Author(s):  
Chen Xu ◽  
Tie Ma ◽  
Hongzan Sun ◽  
Xiaohan Li ◽  
Song Gao

BackgroundFor individuals with cervical cancer, large tumor volume, lymph node metastasis, distant metastasis, and parauterine infiltration are usually associated with a poor prognosis. Individuals with stage 1B1 and 1B2 cervical cancer usually do not have these unfavorable prognostic factors. Once the disease progresses, the prognosis becomes extremely poor. Therefore, investigating the prognostic markers of these cervical cancer patients is necessary for treatment.MethodsThis retrospective study included 95 cervical cancer patients treated with surgery. The patients were divided into progressor and non-progressor groups according to postoperative follow-up results. T-test (or Mann−Whitney U test), chi-squared test (or Fisher’s exact test) and receiver operating characteristic (ROC) curves were used to evaluate imaging, hematology, and clinicopathological index differences between the two groups. Cox analysis was performed to select the independent markers of progression-free survival (PFS) when developing the nomogram. Validation of the nomogram was performed with 1000 bootstrapped samples. The performance of the nomogram was validated with ROC curves, generated calibration curves, and Kaplan-Meier and decision curve analysis (DCA).ResultsCervical stromal invasion depth, lymphovascular space invasion (LVSI), human papilloma virus (HPV-16), Glut1, D-dimer, SUVmax and SUVpeak showed significant differences between the two groups. Multivariate Cox proportional hazard model showed SUVpeak (p = 0.012), and HPV-16 (p = 0.007) were independent risk factors and were used to develop the nomogram for predicting PFS. The ROC curves, Kaplan-Meier method, calibration curves and DCA indicated satisfactory accuracy, agreement, and clinical usefulness, respectively.ConclusionsSUVpeak level (≥7.63 g/cm3) and HPV-16 negative status before surgery were associated with worse PFS for patients with cervical cancer. Based on this result, we constructed the nomogram and showed satisfactory performance. Clinically, individualized clinical decision-making can be performed on patients based on this result.


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