Clinical Stage Of Cervical Cancer Research Articles

Evaluation of Cervical Cancer Staging Based on Magnetic Resonance Imaging in Comparison with Surgical Staging

Background: Cervical cancer is prevalent cancer among women that correct diagnosis has very important role in its treatment. Objectives: The aim of this study was to evaluate the accuracy of magnetic resonance imaging (MRI) in comparison with surgical staging. Also, we compared the accuracy of physical examination with surgical pathology. Methods: This retrospective cross-sectional study was performed on women who had cervical cancer from the start of 2017 to the end of 2021. Age, tumor pathology report (squamous cell carcinoma, clear cell carcinoma, adenocarcinoma, and small cell carcinoma), stage of the tumor, involvement of vagina, uterine, and parametrium, cervical stroma invasion, mass size, pelvic and abductor lymph node metastasis were extracted from the patient’s data and all were evaluated. The pathology report was considered as the gold standard. Results: Eighty women with cervical cancer were evaluated and the mean age was 47.3 years. There was a statistically significant difference between the different prevalence of disease stages (P-value = 0.035) and also stage diagnosis between the three methods (P-value = 0.0004). The diagnostic accuracy of physical examination and MRI in terms of vaginal involvement, parametrium involvement, and uterine involvement were 97.5% and 98.7%; 98.7% and 96.2%; 94.9% and 93.6%; respectively. Conclusions: Magnetic resonance imaging is a good method for the assessment of the clinical staging of cervical cancer and its accuracy is more than 94% in the diagnosis of different parts of cervical cancer involvement.

Application of MRI and CT Images in Surgical Treatment of Early Cervical Cancer.

In order to understand the problems of the application of MRI and CT images in the early cervical cancer surgery, a method that the application of MRI imaging and CT images in early cervical cancer surgery was proposed. For the cervical cancer in clinical practice, the applications of the modern imaging examination and the clinical staging classification were investigated and analyzed. Compared with the surgical pathology results, the application value of common modern imaging in clinical staging of cervical cancer was evaluated. It was found that the sensitivity of MRI and CT in diagnosing lymph node metastasis was 56% and 58%, and the specificity was 93% and 92%, respectively. The experiment proved the application value of MRI and CT in clinical staging of cervical cancer.

The Adler grade by Doppler ultrasound is associated with clinical pathology of cervical cancer: Implication for clinical management

ObjectiveTo analyze the relationship of Adler grade by transvaginal color Doppler flow imaging (TV-CDFI) and the clinical pathological parameters of patients with cervical cancer, and to identify the value of Adler grade in the diagnosis and treatment of cervical cancer.MethodsPatients with cervical cancer diagnosed pathologically in our hospital from January 1, 2019 to December 31, 2019 were included, All patients underwent TV-CDFI examination, and the images were divided into 0 to III grades according to the Adler grades, and the correlations between the Adler classification and clinical pathological parameters (clinical stage, mass size, pathological type, squamous cell carcinoma subtype, CA125, CA199) were analyzed.ResultsA total of 162 patients with cervical cancer were included. With the increase of Adler severity, the clinical stage of cervical cancer increased accordingly. the cancer size differed significantly in patients with different Adler grade (p = 0.004); There were significant differences in the level of CA125, CA199 between the squamous cell carcinoma and adenocarcinoma (all p<0.05). the Adler grade was positively related with the clinical stage, pathological type and squamous cell carcinoma subtypes of cervical cancer (all p<0.05), no correlations were found among the Adler grade and the cancer size, CA125, CA199 (all p>0.05). The area under ROC curve of the cervical squamous cell carcinoma predicted by Adler grade based on FIGO results and pathological results was 0.811and 0.762 respectively (all p<0.05).ConclusionsAdler grades are closely associated with the clinical pathology of cervical cancer, which may be a convenient and effective approach for the assisting assessment of cervical cancer.

Application of MRI in the diagnosis of cervical cancer

Objective: Investigating the diagnostic value of MRI for cervical cancer, including preoperative staging, vagina involvement and lymph node metastasis is the aim of this pape. Methods: Select 116 patients with UCC of the second hospital of JiLin University from October 2016 to April 2019. All patients accept MRI examination. Ultimately, all patients accept surgical treatment. Use SPSS19.0 software to analyze MRI results of all the patients.Using the postoperative pathological results as the golden standard in the diagnosis of cervicalcancer diagnosis. The dates from the MRI preoperative staging, preoperative clinical staging and the postoperative pathologic staging were compared through chi-square test. And the dates of preoperative MRI in cervical cancer vagina involvement and lymph node metastasis diagnosis and postoperative pathological results were compared through Mcnemar chi-square test. The difference was statistically significant(P<0.05). Results: 1, The differences between MRI staging and the postoperative pathologic staging have no statistical significance (P>0.05), whilethe difference between MRI staging and preoperative clinical staging during was statistically significant (P<0.05). Using the postoperative pathological staging as the examination standards, the accuracy of preoperative clinical staging is only 67.5%, and cervical cancer overall preoperative MRI staging accuracy was 95%; 2, Preoperative MRI diagnosis and postoperative pathologic results in cervical vaginal involvement and lymph node metastasis has highsensitivity and specificity, were 97.0%, 96.2%, 93.2%, 97.8%. Checked by Mcnemar chi-square test, the differences between themhave no statisticalsignificance (P>0.05), namely the preoperative MRI diagnosis and postoperative pathological results have consistency in clinical. Conclusion: The combination of MRI and FIGO clinical stage can impro the accuracy of clinical staging of cervical cancer. MRI can be used as the important tool to assess cervical cancer preoperative staging, and to choose and formulate reasonable cervical cancer treatment plan.

High post‐treatment serum soluble receptor‐binding cancer antigen expressed on SiSo cells (sRCAS1) levels is associated with poor survival of patients with cervical cancer

Receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) is responsible for induction of selective immunosuppression. In addition, preclinical studies have shown that sRCAS1 levels may reflect cancer aggressiveness. The main aim of our study was to analyze pre- and post-treatment levels of sRCAS1 in the sera of patients treated for cervical cancer and to evaluate whether the levels change during treatment and their impact on patient prognosis. The study included 49 patients suffering from cervical cancer. The early stage cervical cancer patients (14) were treated surgically, while the advanced stage patients (35) underwent radiochemotherapy. Serum sRCAS1 levels were evaluated both before and after intervention with the use of the ELISA method. We have found that median serum sRCAS1 levels of patients before intervention were not significantly different from the levels assessed after intervention. There were also no differences when pre- and post-treatment levels were compared within the group of early and of advanced stage patients. Serum sRCAS1 levels were not influenced by either the histopathological type of the tumor or the methods of treatment. High post-intervention sRCAS1 levels indicated shortened OS when compared to low sRCAS1 levels. Neither pre-intervention sRCAS1 levels nor the alteration in sRCAS1 levels during treatment were associated with patient prognosis. In multivariate analysis, post-treatment sRCAS1 levels and clinical stage of cervical cancer remained as independent predictors of survival. High post-treatment serum sRCAS1 level in cervical cancer patients seems to be a negative prognostic factor for patient overall survival.

Primary Malignant Lymphoma of Cervix: A Case Report

Background:Primary malignant lymphoma of the uterine cervix is extremely rare and can be misdiagnosed due to its different clinical presentations. The aim of this report was to introduce a case of primary malignant lymphoma of the uterine cervix which was misdiagnosed as an ovarian cyst on ultrasonography. Case report: A 31-year-old female referred with a chief complaint of abnormal uterine bleeding. The ultrasound findings showed a suspicious malignant ovarian mass and the examinations demonstrated a large cervical mass which was considered as stage IB2 in the clinical staging of cervical cancer. However, a biopsy confirmed the presence of non-Hodgkin's B cell lymphoma of the cervix. Systemic chemotherapy followed by CHOP regimen (cyclophosphamide, adriamycin, vincristine, added to rituximab and prednisolone) was started based on the diagnosis. On the 14th month of serial follow-up, the patient was disease-free with no signs of a recurrence. Conclusion: A pelvic examination in patients with vaginal bleeding, vaginal discharge, and pelvic discomfort should be considered as the first step after taking the patient's medical history.

Retrospective Analysis of Cervical Cancer Staging in two Cohorts and its Application in 2018 Revised FIGO Staging for Cancer Cervix

Introduction: cervical cancer is the second most common cancer of women in Bangladesh. Information about the extent of any cancer is critical for treatment planning .For the management of cervical cancer clinical staging is the first and foremost task and disease stage is the single most important prognostic factor.&#x0D; Objective: To know the distribution of clinical stages of cervical cancer, to validate the revised 2018 FIGO staging system for cervical cancer with a particular focus on stage 1B and to know the differences in distribution of stages among two cohort groups.&#x0D; Methods: Retrospective analysis was conducted among two cohorts of cervical cancer patients. First group of cervical cancer patients underwent Examination Under Anesthesia (EUA) for clinical staging during December 2011 to July 2017 and second cohort was the same type of patients undergoing same procedure by different group of observer from August 2017 to June 2019. Chi square test was done to know the difference in stages between two groups. P value &lt;0.05 was considered as significant difference.&#x0D; Results: In the first (8.12.11-1.7.17) cohort ( n—479) maximum ( 68.21%) patients were between 41 to 60 years old. Similarly in the second ( 2.8.17—30.6.19 ) cohort ( n—256) maximum ( 63.45%) patients were between 41 to 60 years of age. Significant difference observed in the measurement of the size of the tumour when it was 2.1 to 4 cm in size. ( p value-0.001) . Great difference observed in performing cystoscopy during EUA ( p value -0.001) between two cohorts. In the first cohort 27.39% and in 2nd cohort only 2.73% patients underwent cystoscopy. Differences also observed in diagnosing stage 11A, B and 4 A diseases.&#x0D; Conclusion : The 2018 FIGO staging system for cervical cancer is useful to distinguish stage 1B disease and it is very fruitful in taking decision regarding management. An important information obtained from this analysis is that great variation can occur in diagnosing stages of cervical cancer by different group of observer.&#x0D; Bangladesh J Obstet Gynaecol, 2019; Vol. 34(2): 87-92

Associations among Serum Lipocalin-2 Concentration, Human Papilloma Virus and Clinical Stage of Cervical Cancer.

Background and objective: Lipocalin 2 (LCN2) has an oncogenic role in promoting tumorigenesis through enhancing tumor cell proliferation and the metastatic potential. The aim of our study was to determine whether serum LCN2 could serve as a diagnostic marker of cervical cancer (CC) and to evaluate the correlation between its serum concentration, the clinical stage of the cancer and Human Papilloma Virus HPV infections in women. Materials and methods: A total of 33 women with histologically proven cervical cancer (CC), 9 women with high- grade cervical intraepithelial neoplasia (HSIL) and 48 healthy women (NILM) were involved in the study. A concentration of LCN2 was assayed with the Magnetic LuminexR Assay multiplex kit. An HPV genotyping kit was used for the detection and differentiation of 15 high-risk (HR) HPV types in the liquid-based cytology medium (LBCM) and the tissue biopsy. Results: The majority (84.8%) of the women were infected by HPV16 in the CC group, and there was no woman with HPV16 in the control group (P < 0.01). Several types of HR HPV were found more often in the LBCM compared to in the tissue biopsy (P = 0.044). HPV16 was more frequently detected in the tissue biopsy than the LBCM (P < 0.05). The LCN2 level was higher in HPV-positive than in HPV-negative women (P = 0.029). The LCN2 concentration was significantly higher in women with stage IV than those with stage I CC (P = 0.021). Conclusions: Many HR HPV types, together with HPV16/18, can colonize the vagina and cervix, but often HPV16 alone penetrates into the tissue and causes CC. The serum LCN2 concentration was found to be associated not only with HR HPV infection, irrespective of the degree of cervical intraepithelial changes, but also with advanced clinical CC stage. LCN2 could be used to identify patients with advanced disease, who require a more aggressive treatment.

Study on value of ultrasonic elastography in diagnosis of clinical staging of cervical cancer and efficacy evaluation of radiotherapy.

The aim of this study was to investigate the application of ultrasonic elastography in the diagnosis of the clinical staging of cervical cancer (CC) and its evaluation value of the treatment effect of CC. A total of 160 suspected CC patients treated in our hospital from September 2016 to March 2018 were collected. Transvaginal conventional ultrasound and ultrasonic elastography were performed on patients to compare the results of the two in the diagnosis of the pathology and clinical staging of CC. Radiotherapy was used for patients confirmed as CC75 in 160 suspected CC patients. The value difference of strain ratio (SR) between conventional ultrasound and elastic ultrasound in the efficacy evaluation of CC patients was compared. The sensitivity (94.67%), specificity (92.94%) and diagnostic accordance rate (93.75%) of ultrasonic elastography for CC were significantly higher than those of conventional ultrasound, with a statistically significant difference (P<0.001). The sensitivity and diagnostic accordance rate of ultrasonic elastography for the pathological diagnosis of CC in stage III and IV were significantly higher than those of conventional ultrasound, with a statistically significant difference (P<0.05). The sensitivity, specificity and diagnostic accordance rate of elastic ultrasound SR value in the efficacy evaluation of radiotherapy in CC patients were higher than those of conventional ultrasound. Except for the specificity, the other two P-values were <0.05, with a statistically significant difference. The elastography images of different stages of CC have some characteristic features. Ultrasonic elastography has a certain clinical value for the diagnosis and efficacy evaluation of CC.

MRI of cervical cancer with a surgical perspective: staging, prognostic implications and pitfalls.

Magnetic resonance imaging (MRI) of the pelvis is the most reliable imaging modality for staging, treatment planning, and follow-up of cervical cancer; and its findings may now be incorporated into the International Federation of Gynecology and Obstetrics Federation (FIGO) 2018 clinical staging of cervical cancer. It is imperative that radiologists are familiar with the imaging appearance of the different stages of cervical cancer as well as the post-treatment changes and imaging pitfalls given the respective clinical manifestations, treatment regimens, and prognosis of an accurate diagnosis. In addition to the different stages of cervical cancer, we address the imaging techniques for diagnosis, staging and treatment implications as well as the changes of the new FIGO staging system. The use of MRI to diagnose and stage cervical cancer is steadily increasing and the new FIGO stagi ng system, previously based on clinical examination, now allows the staging or change of staging based on the imaging findings. MRI can evaluate the extent of disease because of its excellent contrast resolution for pelvic tissues and organs, high accuracy and detailed elaboration of the cervical/uterovaginal anatomy. Relevant anatomy, including normal MRI appearance of the cervix, parametria and pelvic ligaments; different stages of cervical cancer on MRI with prognostic and therapeutic implications; MRI sequences, other imaging modalities used in the staging and follow-up, treatment of different stages and the appearance of the cervix and cervical cancer post-treatment. Since clinical implications and therapeutic strategies for cervical cancer treatment vary tremendously according to degree of tumor extension, familiarity with relevant MRI techniques and findings is essential for radiologists. It is important that radiologists interpreting pelvic MRI are aware with the different stages of cervical cancer to provide useful information regarding treatment and prognosis. Pitfalls regarding the interpretation of tumor extension can interfere with an accurate diagnosis and have significant therapeutic implications.

MicroRNA‑130a regulated by HPV18 E6 promotes proliferation and invasion of cervical cancer cells by targeting TIMP2

Human papillomaviruses (HPVs) have important roles in the development and progression of cervical cancer, but the underlying mechanisms are yet to be fully elucidated. MicroRNA-130a (miR-130a) has previously been reported to promote cervical cancer growth. However, the underlying molecular mechanisms by which miR-130a promotes cervical cancer progression have remained largely elusive. In the present study, polymerase chain reaction and western blot analyses were performed to examine the expression levels of miR-130a and associated proteins. A wound healing assay and a Transwell assay were applied to study cell migration and invasion. A luciferase reporter gene assay was performed to confirm the targeting associations of miR-130a. It was observed that miR-130a was significantly upregulated in cervical cancer tissues compared with that in adjacent non-tumorous tissues. High expression of miR-130a was significantly associated with lymph node metastasis and an advanced clinical stage of cervical cancer. Furthermore, the expression of miR-130a was also higher in HPV(+) cervical cancer cell lines compared with that in HPV(-) cells. Knockdown of HPV18 E6 significantly inhibited the expression of miR-130a in HeLa cervical cancer cells. Furthermore, knockdown of miR-130a reduced the migration and invasion of HeLa cells. Tissue inhibitor of metalloproteinase 2 (TIMP2), an antagonist of matrix metalloproteinase 2 (MMP2), was identified as a novel, direct target gene of miR-130a. The expression of TIMP2 was negatively mediated by miR-130a, and HPV18 E6 inhibited the expression of TIMP2 in HeLa cells. Furthermore, knockdown of TIMP2 rescued the suppressive effects of miR-130a downregulation on the migration and invasion of HeLa cells. In summary, the present study suggests that HPV18 E6 promotes the expression of miR-130a, which further inhibits the expression of TIMP2 and promotes cervical cancer cell invasion. Therefore, HPV/miR-130a/TIMP2 signaling may be a potential target for the prevention of cervical cancer metastasis.

THE ROLE OF CYSTOSCOPY IN THE STAGING OF CERVICAL CANCER

(Objectives) For the staging of cervical cancer, we investigated the relationship between computed tomography/magnetic resonance imaging (CT/MRI) and cystoscopy and evaluated the need for cystoscopy to diagnose bladder invasion resulting from cervical cancer. (Patients and Methods) We retrospectively reviewed the patients who underwent cystoscopy because of a diagnosis of bladder invasion of cervical cancer from April 2012 to March 2017 in our hospital. A total of 217 women (median age 53 years old) underwent cystoscopy. We also reviewed whether or not there were findings showing bladder wall infiltration on CT/MRI and cystoscopy. (Results) CT was performed in all cases, and MRI was performed in 216 cases. Seventy cases were judged to have possible bladder infiltration by CT, and 35 were judged to have possible bladder infiltration by MRI. In cystoscopy, 24 cases were reported to have "suspicion of bladder invasion" by urologists, but only 12 cases had bladder mucosal findings with "ridges and furrows" (defined as bladder infiltration without a bladder biopsy in this study). The sensitivity and negative predictive values of CT/MRI were both 100%. Only one case underwent a bladder biopsy, and the histological diagnosis was cystitis. (Conclusions) The findings of our investigation suggested that cystoscopy is not required when there were no obvious findings of bladder invasion by CT/MRI at the clinical staging of cervical cancer.

Expression of IRX1 in cervical cancer and its correlation with clinical stage of cervical cancer

Objective: To study the expression of IRX1 (Iroquois homeobox gene) in cervical cancer and its correlation with clinical stage of cervical cancer. Methods: A total of 61 patients with cervical cancer from January 2015 to January 2017 were enrolled in this study, of which 15 were classified as phase Ⅰ of cervical cancer, 22 patients were classified as phase Ⅱ, 19 cases were classified as phase Ⅲ, 5 cases were classified as phase Ⅳ followed FIGO staging criteria.The expression of IRX1 protein in Hela, C4-1 and Siha cell lines were detected by Western blot compared with the normal human cervical epithelial cells HCerEpiC.Collected cancerous tissue of cervical cancer as experimental samples, the expression of IRX1 mRNA in cancer tissues and paracancerous tissue were detected by qPCR.Immunohistochemistry was used to detect the expression of IRX1 in different stages of cervical cancer, the correlation between IRX1 expression and clinical stage was analyzed. Results: The results of Western blot showed that IRX1 expression in cervical cancer cells were higher than that in normal cervical epithelial cells, and the results of qPCR also showed that the expression of IRX1 increased with the stage of cancer at the gene level.The difference was statistically significant.The expression of IRX1 in the nucleus and cytoplasm were detected by immunohistochemistry.Immunohistochemical results showed that the higher the stage of cancer was, the higher the expression rate of IRX1 was. Conclusion: IRX1 expression is associated with the clinical stage of cervical cancer, suggesting that IRX1 may be involved in the development and progression of cervical cancer.IRX1 is expected to be a new molecular target for the diagnosis and treatment of cervical cancer. This study will provide a new theoretical basis for the treatment of cervical cancer.

Aberrant frequency of TNFR2+ Treg and related cytokines in patients with CIN and cervical cancer.

Regulatory T (Treg) cells expressing tumor necrosis factor receptor 2 (TNFR2) are highly suppressive and are associated with immune homeostasis in various diseases. However, the role of TNFR2+Treg subset and relevant cytokines in the development of cervical cancer (CC) remained unclear. In this study, 72 patients with CC, 30 patients with cervical intraepithelial neoplasia (CIN) and 30 healthy volunteers were enrolled. The level of circulating TNFR2+Tregs was investigated through flow cytometry. The plasma concentrations of soluble TNFR1 (s-TNFR1) and soluble TNFR2 (s-TNFR2) were determined by enzyme-linked immunosorbent assay. In addition, the mRNA expression levels of TNF-α, TNFR1, TNFR2, and Foxp3 were measured using real-time polymerase chain reaction. Results showed that both peripheral and tumor infiltrating TNFR2+Tregs significantly increased in patients with CIN and CC and levels of circulating s-TNFR1 and s-TNFR2 increased in patients with CC. Moreover, the percentage of peripheral TNFR2+Tregs was inversely correlated with the clinical stages of CC. Furthermore, the mRNA expression levels of TNF-α, TNFR2, and Foxp3 increased in patients with CIN and CC. Overall, these results indicate that TNFR2+Tregs and relevant cytokines contribute to CC development and are promising targets in future immunotherapeutic approaches.

PBX3 is associated with proliferation and poor prognosis in patients with cervical cancer.

Pre-B-cell leukemia homeobox 3 (PBX3) is upregulated in various malignancies; however, the role of PBX3 in cervical cancer (CC) is unknown. The purpose of this study was to explore the expression characteristics, clinicopathological significance, and molecular biological function of PBX3 in CC. The expression levels of PBX3 were analyzed in CC cell lines and tumor specimens by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining. The clinicopathological characteristics associated with PBX3 expression were evaluated. An RNA interference approach was employed to suppress PBX3 expression in CC in vitro and in vivo, determine its role in cell proliferation and analyze its molecular function. We found that PBX3 expression was significantly upregulated in CC cell lines and clinical specimens compared with normal cells and adjacent nontumorous cervical tissues. PBX3 was an independent predictive factor of poor prognosis, and its expression was correlated with tumor diameter, pathological grading, lymph node metastasis, invasion depth, vascular invasion, and clinical stage of CC. Multivariate analysis suggested that PBX3 expression may represent an independent prognostic indicator of the survival of CC patients. CC patients with high PBX3 expression exhibited reduced overall survival compared with those with low PBX3 expression. Additionally, stable downregulation of PBX3 expression in CC cell lines suppressed cell proliferation and decreased p-AKT protein expression levels in vitro. Similarly, in vivo assays demonstrated that PBX3 downregulation in CC cells markedly inhibited tumor size and weight. Overall, we demonstrated that PBX3 can promote CC cell proliferation via the AKT signaling pathway and that it may serve as a prognostic marker. Our data indicate that inactivation of PBX3 may be an effective clinical treatment for CC.

Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer

Axl receptor tyrosine kinase is involved in the tumorigenesis and metastasis of many cancers. Axl expression was markedly higher in human papilloma virus type 16E6 (HPV16E6)-overexpressing HeLa (HE6F) cells and lower in HPV16E6-suppressing CaSki (CE6R) cells than in the controls. SiRNA-mediated knockdown of E6 expression led to increased phosphatase and tensin homolog (PTEN) phosphorylation at Ser380 and attenuated AKT phosphorylation. Expression of membrane-associated guanylate kinase inverted-2 (MAGI-2), an E6-induced degradation target, was induced in E6-siRNA-transfected cells. Moreover, myeloid zinc finger protein 1 (MZF1) binds directly to the Axl promoter in HE6F cells. Axl expression was regulated by HPV16E6-mediated PTEN/AKT signalling pathway, and Axl promoter activity was regulated through MZF1 activation in cervical cancer, which promoted malignancy. Axl silencing suppressed the metastasis of Caski cells and enhanced the susceptibility to NK cell-mediated killing of HE6F cells. In addition, the expression of Axl and MZF1 was highly correlated with clinical stage of cervical cancer and HPV16/18 infection. Taken together, Axl expression was induced by HPV16E6 in cervical cancer cells, suggesting that blockade of Axl signalling might be an effective way to reduce the progression of cervical cancer.

Long Noncoding RNA GAS5, Which Acts as a Tumor Suppressor via microRNA 21, Regulates Cisplatin Resistance Expression in Cervical Cancer.

ObjectivesThe aims of this study were to investigate the functions of GAS5 as a tumor suppressor in cervical cancer and explore the mechanism.MethodsThe expression of GAS5 and microRNA 21 (miR-21) was detected in primary cervical cancer tissue specimens, as well as in cervical cancer cell lines. We identified the interaction of GAS5 and miR-21 by quantitative polymerase chain reaction, Western blot, and dual-luciferase reporter assay. We also studied the functions of GAS5 in proliferation, apoptosis, migration, and invasion in cervical cancer cells in vitro and vivo. Finally, the impact of GAS5 on cisplatin resistance and its mechanism in cervical cancer cells was also identified.ResultsThe expression of GAS5 and miR-21 was detected in primary cervical cancer tissue specimens, as well as in cervical cancer cell lines. GAS5, which is a tumor suppressor playing roles in inhibiting the malignancy of cervical cancer cells, including proliferation in vivo and vitro, migration, and invasion, has a low expression in cervical cancer tissue and cervical cancer cell lines, whereas miR-21 expression is high. GAS5 significantly decreased the expression of miR-21, and there is a reciprocal repression of gene expression between GAS5 and miR-21. Besides, most importantly, we found that high expression of GAS5 and low expression of miR-21 can enhance the sensitivity of SiHa/cDDP cancer cells to cisplatin. A further experiment for identifying the mechanism of cisplatin resistance by GAS5 showed that GAS5 can not only regulate phosphatase and tensin homolog through miR-21 but also influence the phosphorylation of Akt.ConclusionsOur results indicate that GAS5 is a direct target of miR-21 and can predict the clinical staging of cervical cancer. Most importantly, GAS5 can also influence cisplatin resistance in cervical cancer via regulating the phosphorylation of Akt. All of these suggest that GAS5 may be a novel therapeutic target for treating cervical cancer.

Elevated Homocysteine, an Emerging Biomarker for Cervical Cancer, A Case-Controlled Study

Background: Elevated homocysteine, an emerging biomarker for cervical cancer is amenable to treatment by cheap and effective nutritional interventions. Methods: From April 2012 through September 2012, a case-controlled study was performed in the Gynae oncology unit of Bangabandhu Sheikh Mujib Medical University (BSMMU) and the National Institute of Cancer Research and Hospital (NICR &amp; H), in Dhaka, Bangladesh. The objectives were to measure the serum homocysteine levels in women with squamous cell carcinoma of the cervix and in normal controls. Fifty women with invasive squamous cell carcinoma and 50 normal controls were compared for demographic and socioeconomic differences. Blood was tested for homocysteine levels. Results: Among cases of cervical cancer, 82% had homocysteine level between 4.5-15 µmol/L &amp; 14% had high homocysteine level (&gt;15 µmol/L). Whereas in control group, 98% had homocysteine level between 4.5-15 µmol/L and 2% had homocysteine &lt;4.5 µmol/L (low). High level of homocysteine (&gt;15 µmol/L) was not observed in any patient in the control group. The mean homocysteine level in cervical cancer patients was also higher (10.88 ?mol/L) than that of controls (8.50 µmol/L) and this difference was statistically significant. Histological grade and clinical stage of cervical cancer did not correlate with serum homocysteine level. Conclusion: There is a difference in homocysteine levels in women with cervical cancer. Homocysteine, which is associated with nutritional deficiencies of fruits and vegetables, may play a role as a marker for or as a co-factor in malignant transformation of cervical squamous epithelium. Larger studies are needed to further study this association. However public awareness is important regarding the role of fresh vegetables and fruits containing vitamin B (folate-vitamin B9; vitamin B12; vitamin B6) to reduce homocysteine and its possible consequences of cancer prevention.

Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway

Loss of Chr9q31-33 is one of the most common chromosome imbalances of cervical cancer, but the underlying mechanism has not been well documented. The loss of heterozygosity (LOH) status of Chr9q31-33 was investigated utilizing 26 microsatellite markers. We detected the expression of miR-181a2/181b2 by qRT-PCR analysis of cervical cancer cell lines and 100 paired tumor samples and corresponding adjacent non-tumor tissues. Kaplan-Meier and Cox proportional hazard regression analyses were performed to identify the prognostic value of miR-181a2/181b2. Regulation of expression was analyzed by methylation-specific PCR. The tumor-suppressing effects of miR-181a2/181b2 were determined in vitro and in vivo The target gene and signaling pathway that mediated the function of miR-181a2/181b2 were also identified. Chr9q33.3 was identified as one of the most deleted regions in cervical cancer. Underexpression of miR-181a2/181b2 was detected in 46% of cervical cancer and was induced by the LOH of chr9q33.3 and promoter hypermethylation. Attenuated miR-181a2/181b2 expression predicted a poor prognostic phenotype and advanced clinical stage of cervical cancer. miR-181a2/181b2 prominently dampened cell-cycle progression, suppressed cell growth, and promoted apoptosis of tumor cells in vitro They also effectively impeded tumor formation and growth in vivo miR-181a2/181b2 exert the tumor suppressor ability by depressing the direct target PIK3R3 (p55γ) and consequently modulating the PIK3R3/Akt/FoxO signaling pathway. We demonstrated a cause-and-effect event beginning from loss of chr9q33.3, a frequent event in cervical cancer, to the underexpression of miR-181a2/181b2, leading to the elevated activation of the PI3K pathway. Clin Cancer Res; 23(2); 575-86. ©2016 AACR.

Lymphangiogenesis in cervical cancer evaluated by expression of the VEGF-C gene in clinical stage IB-IIIB.

IntroductionThe aim of the present study was to evaluate the profile of VEGF-C gene expression in particular stages of cervical cancer (IB-IIIB) and to estimate the correlation between VEGF-C mRNA quantity profile and clinical stage.Material and methodsMaterial for molecular analysis consisted of cervical cancer tissue specimens collected from 38 women (10, 15, 13 cases were classified as IB, IIB and IIIB, respectively). The control group was composed of normal cervical tissues collected from 10 women who underwent hysterectomy for non-oncological reasons. The number of VEGF-C mRNA copies in particular groups was estimated by the reverse transcription quantitative polymerase chain reaction (RT-qPCR) method.ResultsIn the control group the average number of mRNA copies was 134 ± 36 (median: 106), in a group with stage IB it was 16 077 ± 7090 (median: 580), for stage IIB – 35 019 ± 8945 (median: 40 870). The highest number of mRNA VEGF-C copies was derived in a group of patients with cervical cancer of stage IIIB. The average quantity was 56 155 ± 12 470, whereas median 55 981. A statistically significantly higher level of VEGF-C gene expression was disclosed in cervical cancer specimens with stage IIB and IIIB than in the control group. In stage IIIB, the VEGF-C gene expression was significantly higher than in specimens derived from individuals in stage IB.ConclusionsIn squamous cell carcinoma of the uterine cervix of stage IB-IIIB genes involved in lymphangiogenesis, especially VEGF-C, are expressed, which expression increases as the clinical stage of cervical cancer is higher.