Expression In Cervical Carcinomas Research Articles

Expression of e-cadherin and Ki-67 in cervical cancer: a study in a tertiary care hospital, Dhaka, Bangladesh

Background: Cervical cancer, ranking as the second most prevalent cancer and a leading cause of female cancer-related deaths in low to middle-income nations, exhibits a notable connection between tumor proliferation (Ki-67) and invasiveness (e-cadherin). Both factors contribute significantly to cervical cancer's aggressiveness. This study aims to establish the clinical-pathological link between e-cadherin and Ki-67 expression in cervical carcinoma, and assess their potential as diagnostic biomarkers. Methods: This cross-sectional study spanned July 2017 to June 2019 at Sir Salimullah Medical College and Mitford Hospital Dhaka. It encompassed 60 adult female patients histopathologically diagnosed with cervical cancer. All patients underwent e-cadherin, Ki-67 expression assessments, and histopathological diagnosis. Ethical clearance was granted by SSMC Institutional Ethics Committee. Results: E-cadherin expression presented as follows: strong intensity in 36.7% cases, weak and homogeneous in 35.0%, weak and heterogeneous in 8.3%, negative staining in 15.1%, and negative expression in 5.0%. Ki-67 mean levels varied significantly among different types of cervical cancer (p<0.05). Squamous cell carcinoma was predominant (80.0%), with heightened e-cadherin expression in well-differentiated cases (14 cases). Notably, cases with no e-cadherin expression exhibited Ki-67 mean of 71.0±7.9, while those with strong E-cadherin expression displayed Ki-67 mean of 56.5±8.2 (p<0.05). A significant negative correlation (r=-0.300; p=0.022) emerged between Ki-67 LI (%) and e-cadherin expression. Conclusions: E-cadherin correlates effectively with clinicopathological features and Ki-67 expression in cervical carcinoma. This underscores its pivotal role in cervical cancer progression.

IMMUNOHISTOCHEMICAL EXPRESSION OF VIMENTIN IN CERVICAL CARCINOMA AND ITS CORRELATION WITH CLINICOPATHOLOGICAL PARAMETERS

Objective: To evaluate the signicance of vimentin expression in cervical carcinoma and correlate it with various prognostic factors like tumor size, tumor type, histological grade, lymph node status and Ki-67 status. The Prospective study was Material and Methods: carried out in the Department of Pathology of SRMS IMS, Bareilly over a period of 1.5 years from March 2021 to August 2022.Fifty histologically conrmed cervical carcinoma cases were included. The expression of vimentin and Ki67 proteins in cervical carcinoma tissues were assessed using immunohistochemical method. Correlations between vimentin expression with clinicopathological features and Ki67 status were analyzed . Results: Among 50 cases studied, maximum number of patients were diagnosed as squamous cell carcinoma(84%) and rest as adenocarcinoma (16%).Vimentin expression was positive in 28.6% cases of squamous cell carcinoma and 37.5% cases of adenocarcinoma. High Ki67 index was seen in 66.6% cases of SCC and 62.5% cases of adenocarcinoma. No signicant correlation was found between vimentin expression and various clinicopathological features like age, tumor size, tumor type, histological grade, lymph node status and clinical stage.However,there was a weak correlation between the expression of vimentin and Ki67status. Our ndings do not s Conclusion: uggest a possible role of Vimentin expression in progression and prognosis of cervical cancer

Histological analysis of TGFβ1 and VEGFR expression in cervical carcinoma treated with Rhodomyrtus tomentosa

Cervical carcinoma is one of the most common malignant carcinomas around the world, including Indonesia. Rhodomyrtus tomentosa is an herbal medicine that is often used in Asia as a therapeutic agent to stop cancer metastases. The process of neoangiogenesis in cervical cancer depends on VEGFR activity. Increased TGFβ1 production is also linked to cervical cancer, suggesting that gene inactivation contributes to the emergence of cervical carcinoma. Group C- was the control group, Group C+ was the cancer model group, CER100 was the group of rats with cancer + 100 mg/kg body weight (BW) of R. tomentosa, CER200 was the group of rats with cancer + 200 mg/kg BW of R. tomentosa, and CER400 was the group of rats with cancer + 400 mg/kg BWR. tomentosa. Rats were dissected after administration of R. tomentosa for 30 days. Immunohistochemical staining of the cervical tissue was performed with TGFβ1 and VEGFR antibodies. VEGFR expression was significantly different from TGFβ1 expression (p < 0.01). The highest expression was observed at the lowest dose of R. tomentosa (100 mg/kg BW), and the lowest expression was observed at 200 and 400 mg/kg BW. The administration of R. tomentosa can repair tissue damage and decrease the expression of TGFβ1 and VEGFR via histopathological parameters, indicating the importance of the activity of these proteins in the development of neoangiogenesis in cervical cancer.

An Immunohistochemical Study on Ki-67 Expression in Squamous Cell Carcinomas of Cervix With Clinicopathological Correlation.

Background Cervical carcinoma is one of the most prevalent cancers affecting women worldwide. Studies on Ki-67 expression in cervical lesions had focused mainly on the intraepithelial lesions of the cervix and not much on invasive carcinomas. The few studies published so far on Ki-67 expression in invasive cervical carcinomas have shown inconsistent results on the association of Ki-67 with various clinicopathological prognostic factors. Aims and objectives To assess Ki-67 expression in cervical carcinomas and to compare it with various clinicopathological prognostic factors. Materials and methods Fifty cases of invasive squamous cell carcinoma (SCC) were included in the study. Histological patterns and grades were identified and noted in these cases after microscopic examination of the histological sections. Immunohistochemical (IHC) staining with anti-Ki-67 was done and scored from 1+ to 3+. This score was compared with clinicopathological prognostic factors like clinical stage, histological pattern, and grade. Result Among the 50 cases of SCC, 41 showed keratinizing pattern (82%) and nine showed non-keratinizing pattern (18%). Four were in stage I, 25 were in stage II, and 21 were in stage III. Overall, 34 (68%) cases had Ki-67 score 3+, 11 (22%) had Ki-67 score 2+, and five (10%) had Ki-67 score 1+. Ki-67 score of 3+ was the most common score in keratinizing SCC (75.6%), poorly differentiated carcinomas (76.2%), and stage III cases (81%). Conclusion We observed statistically significant correlation of Ki-67 expression with higher clinical stage, keratinizing tumours, and poorly differentiated tumours (p<0.05) indirectly implying the poor prognostic significance of this marker.

Analysis of p21 Expression in Cervical Carcinoma at a Tertiary Institution in Ghana: An Immunohistochemical Study

Abstract Background: Cervical cancer is one of the leading causes of female mortality worldwide. About 85% occur in low-income countries with 13.8% incidence and 14% death in Ghana. p21 has been overexpressed in many cancers. Its overexpression in cervical cancer is linked to tumor growth and a bad prognosis. Aim: The expression profile of p21 in our setting is largely unknown, therefore, the necessity to evaluate p21 expression in cervical cancer. Materials and Methods: A retrospective and descriptive study design was employed to investigate p21 expression in association with demographic and clinicopathological features on formalin-fixed paraffin-embedded cervical cancer tissues. The age, histologic type, and tumor grade of patients were abstracted from the hospital records between January 1, 2015, and December 31, 2016. Tissue microarray of suitable blocks was constructed, and immunohistochemistry was performed. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 26. Results: One hundred and thirty-five cases were used for the study with an age range of 31–115 years and mean age of 58.93 years (standard deviation ± 17.88). Majority of the cases were postmenopausal (40–59 years). Squamous cell carcinoma (SCC) was the most common histological type (96.3%) with the nonkeratinizing variant having the highest frequency (53.1%). Majority of the cases were high grade; Grade 2 (33.3%) and Grade 3 (49.6%). Majority of the cases (66.7%) stained positive for p21 antibody. The associations between p21 and the clinicopathological characteristics were not statistically significant (P &gt; 0.05). p21 was more overexpressed in SCC (64.8%) than adenocarcinoma. Conclusion: An overexpression of p21 in this study suggests that it may contribute to antiapoptosis in cervical cancer leading to tumor progression, aggressive behavior, and poor prognosis.

Correlation of Myc Expression with Wee1 Expression by Zanthoxylum acanthopodium in Cervical Carcinoma Histology.

&lt;b&gt;Background and Objective:&lt;/b&gt; Natural herbs and molecular therapy can be used to treat cervical cancer. The Myc and Wee1 control tumour cell fate and microenvironmental changes like angiogenesis activation and host immune response suppression. The study aims to know about the correlation of Myc and Wee1 expressions as a molecular therapy given by &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt;. &lt;b&gt;Materials and Methods:&lt;/b&gt; There are five rat groups: Group K&lt;sup&gt;&lt;/sup&gt; is the untreated group, Group K&lt;sup&gt;+&lt;/sup&gt; is the rats injected with benzopyrene, Group P&lt;sub&gt;1&lt;/sub&gt; is the administration of &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; 100 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt., Group P&lt;sub&gt;2&lt;/sub&gt; is the administration of &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; 200 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt. and Group P&lt;sub&gt;3&lt;/sub&gt; is the administration of &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; 400 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt. The rats are dissected 30 days after receiving &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt;. To stain the cervical tissues, immunohistochemistry is performed. &lt;b&gt;Results:&lt;/b&gt; &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; administration caused epithelial thickening and decreased Myc expression in previously uncontrolled carcinomas from untreated malignancies, which now slowed and stopped growing into the normal epithelium. Wee1 expression revealed that this herb could repair tissue by drastically reducing Wee1 expression at a dose of 100-400 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt. Similarly, at the highest dose, cervical carcinoma stops growing and the nucleus begins to form normally (p<0.01). &lt;b&gt;Conclusion:&lt;/b&gt; The higher Myc expression on andaliman administration in cervical carcinoma decreases Wee1 expression in cervical carcinoma so these two proteins have a strong and significant correlation. &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; can be administered at various dosages to lower the number of positive indexes of Myc and Wee1 expression in cervical carcinoma.

Expression of PD-L1 and tumor infiltrating lymphocyte markers in uterine cervical carcinoma

Objective: To investigate the expression of PD-L1, CD4, CD8 and CXCL-13 in cervical carcinoma, and their clinicopathological significance was analyzed. Methods: A total of 77 patients with cervical carcinoma in the Seventh Medical Center, PLA General Hospital from January 2019 to December 2021 were included. All patients received radical surgical resection in the Seventh Medical Center of Chinese PLA General Hospital. The expression of PD-L1, CD4, CD8 and CXCL-13 was detected by immunohistochemical (IHC) method. The correlation between IHC markers and patients' clinicopathological parameters was analyzed. Results: There were 59 cases of squamous cell carcinoma and 18 cases of adenocarcinoma (ranging from 29 to 69 years) with an average of (49.4±9.8) years. PD-L1 was expressed in different degrees in cervical squamous cell carcinoma and adenocarcinoma (χ²=4.975, P=0.026); CD4+, CD8+and CXCL-13+tumor infiltrating lymphocytes (TIL) were observed in the carcinoma cell nests and peritumoral stroma. PD-L1 expression in cervical carcinoma was moderately correlated with the number of CD4+TIL in the carcinoma nests, and the number of CD8+, CXCL-13+TIL infiltration in the carcinoma nests and stroma, but not to the patient's age, histologic differentiation, presence or absence of vascular invasion, presence or absence of lymph node metastasis and FIGO stage (P>0.05). Conclusions: The high expression of PD-L1 in cervical carcinoma tissues is closely related to the number of TIL in the carcinoma nests and peritumor stroma, suggesting that they may have important reference value for predicting the response to immunotherapy in patients with cervical carcinoma.

Gene expression profiling identifies the role of Zac1 in cervical cancer metastasis

The zinc-finger protein which regulates apoptosis and cell cycle arrest 1 (Zac1), encoded by Plagl1 gene, is a seven-zinc-finger containing transcription factor belonging to the imprinted genome and is expressed in diverse types of embryonic and adult human tissues. Zac1 is postulated to be a tumor suppressor by inducing cell cycle arrest and apoptosis through interacting and modulating transcriptional activity of p53 as it was named. Correspondingly, the reduction or loss of Zac1 expression is associated with the incidence and progression of several human tumors, including cervical cancer, breast cancer, ovarian cancer, pituitary tumors, and basal cell carcinoma, implying the rationality of utilizing Zac1 expression as novel a biomarker for the evaluation of cervical cancer prognosis. However, to date, it has not been elucidated whether Zac1 expression is related to the prognosis of patients in clinical cervical cancer tumor samples. To address the questions outlined above, we report here a comprehensive investigation of Zac1 expression in biopsies of clinical cervical carcinoma. By analyzing Zac1 expression in various gene expression profiling of cervical cancer databases, we show the association between high Zac1 expression and poor prognosis of cervical cancer. Functional enrichment analysis showed that high Zac1 expression was associated with epithelial-mesenchymal transition (EMT), which was further observed in clinical characteristics and metastatic carcinoma samples using immunohistochemical staining. Correspondingly, hypomethylation of CpG island on Zac1 promoter was observed in samples with high Zac1 expression in cervical carcinoma. Finally, overexpression of Zac1 in a variety of cervical cancer cell lines increase their mesenchymal biomarker expression and migration, strengthening the correlation between cervical cancers with high Zac1 expression and metastasis in clinical. In summary, this research firstly revealed that identifying Zac1 expression or the methylation status of CpG site on Zac1 promoter may provide us with novel indicators for the evaluation of cervical cancer metastasis.

Inhibiting ubiquitin conjugating enzyme E2 N by microRNA-590-3p reduced cell growth of cervical carcinoma.

The ubiquitin conjugating enzyme E2 N (UBE2N) has been reported to be involved in the tumorigenesis of several tumors, but its function in cervical carcinoma has not been investigated yet. In the present study, UBE2N was found elevated in cervical carcinoma, and patients with high UBE2N had a shorter overall survival than patients with low expression. Additionally, knockdown of UBE2N decreased the activation of MEK1/2 and p38 in cervical carcinoma cells, and UBE2N knockdown also markedly inhibited cervical carcinoma cell growth. Our further studies found that microRNA-590-3p (miR-590-3p) was significantly decreased in cervical carcinoma, and patients with high miR-590-3p had a longer overall survival than patients with low expression. Moreover, miR-590-3p expression was found negatively correlated with UBE2N expression in cervical carcinoma, and our further studies showed that miR-590-3p targeted UBE2N and inhibited its expression in cervical carcinoma. Overexpression of miR-590-3p could inhibit cervical carcinoma cell growth, but enhanced UBE2N could rescue miR-590-3p-induced cell growth inhibition in cervical carcinoma. This study indicated that targeting miR-590-3p/UBE2N axis could be a potential strategy for the treatment of cervical carcinoma.

LOXL2 Expression Status Is Correlated With Molecular Characterizations of Cervical Carcinoma and Associated With Poor Cancer Survival via Epithelial-Mesenchymal Transition (EMT) Phenotype.

As molecular analyses based on high-throughput sequencing have developed, the molecular classification of cancer has facilitated clinical work. The aim of the present study was to identify a new potential therapeutic target for cervical carcinoma by molecular analyses. We firstly tested the LOXL2 expression pattern in 50 paired normal cervix and cervical carcinoma via qPCR and immunohistochemistry, and the LOXL2 expression pattern was found to be in accordance with public datasets from Gene Expression Omnibus (GEO). Then, we comprehensively rewired the 176 cervical carcinoma samples from The Cancer Genome Atlas (TCGA), subsequently clustered the samples into two groups corresponding to LOXL2 expression to determined the associations between LOXL2 expression status and molecular characterizations of cervical carcinoma. In vitro assays for further verifying the correlations in SiHa-shLOXL2 and HeLa-shLOXL2 cell lines. In this study, we found that LOXL2 highly expressed in carcinoma tissue, with 14 CpG islands of LOXL2 promoter that were significantly and negatively associated with its expression in cervical carcinoma. And there were notable correlations among LOXL2 expression status and molecular characterizations of cervical carcinoma, including diagnostic age, HPV A7 types, mRNA molecular clusters, miRNA molecular clusters, and DNA methylation molecular clusters et al. In addition, high LOXL2 expression was negatively correlated with lower tumor mutation density, especially in EP300, ERBB2, EGFR and NOTCH2, and was negatively correlated with lower expression of APOBEC3 family genes, such as APOBEC3A, APOBEC3B, APOBEC3D, and APOBEC3G. Furthermore, high LOXL2 expression was associated with poor overall (OS) and poor disease-free survival (DFS) in cervical carcinoma, and was associated with higher epithelial-mesenchymal transition (EMT) score, enrichment of extracellular matrix (ECM) signaling, the phenotype that was found to be associated with poor prognosis in cervical carcinoma from TCGA. Conversely, the ability of cell proliferation and cell migration were reversed in LOXL2 knock-down cervical cell lines via regulating the genes' expression of EMT phenotype in vitro. Overall, we demonstrated the correlation between LOXL2 expression status and cancer molecular characterizations of cervical carcinoma, and identified LOXL2 may serve as a therapeutic target for such carcinoma.

Overexpression of chloride channel-3 (ClC-3) is associated with human cervical carcinoma development and prognosis

BackgroundCervical carcinoma is a major gynecological cancer and causes cancer-related deaths in worldwide, the latent pathogenesis and progress of cervical cancer is still under research. ClC-3 may be an important promoter for aggressive metastasis of malignant tumors. In this research, we explore the ClC-3 expression in cervical carcinoma and its underlying clinical significance, trying to illuminate ClC-3 probable function in the neoplasm malignant behavior, development and prognosis.MethodsParaffin-embedded cervical (n = 168) and lymph node (n = 100) tissue specimens were analysed by immunohistochemistry. Fresh human cervical tissue specimens (n = 165) and four human cervical cell lines were tested for ClC-3 mRNA and protein expression levels by quantitative real-time PCR and western blotting. The relationship between the expression levels of ClC-3, the pathological characteristics of the carcinoma, and the clinical prognosis were statistically analysed.ResultsIn normal and precancerous (LSIL, HSIL) cervical tissues as well as cervical carcinoma tissues, both ClC-3 mRNA and protein expression levels increased significantly (p < 0.05). The expression level of ClC-3 was closely-related to the histological differentiation (p = 0.029), tumour staging (p = 0.016), tumour size (p = 0.039), vascular invasion (p = 0.045), interstitial infiltration depth (p = 0.012), lymphatic metastasis (p = 0.036), and HPV infection (p = 0.022). In an in vitro experiment, ClC-3 mRNA and protein were found to be overexpressed both in the HeLa and SiHa cell lines, but low expression levels were detected in the C-33A and H8 cell lines (p < 0.05). Furthermore, the high expression levels of ClC-3 was significantly correlated to poor survival in cervical carcinoma patients (Log-rank test, p = 0.046).ConclusionsThese data suggest that overexpression of ClC-3 is closely associated with human cervical carcinoma progression and poor prognosis; this suggests that ClC-3 may function as a patent tumour biomarker and a latent therapeutic target for cervical carcinoma patients.

Human Papillomavirus 16 Oncoproteins Downregulate the Expression of miR-148a-3p, miR-190a-5p, and miR-199b-5p in Cervical Cancer.

Almost all cervical cancers are associated with human papillomavirus (HPV); however, the majority of women infected with this virus do not develop cervical cancer. Therefore, new markers are needed for reliable screening of cervical cancer, especially in relation to HPV infection. We aimed to identify potential microRNAs that may serve as diagnostic markers for cervical cancer development in high-risk HPV-positive patients. We evaluated the microRNA expression profiles in 12 cervical tissues using the hybridization method and verified them by quantitative polymerase chain reaction (qPCR). Finally, we evaluated the effects of HPV16 oncoproteins on the expression of selected microRNAs using cervical cancer cells (CaSki and SiHa) and RNA interference. With the hybridization method, eight microRNAs (miR-9-5p, miR-136-5p, miR-148a-3p, miR-190a-5p, miR-199b-5p, miR-382-5p, miR-597-5p, and miR-655-3p) were found to be expressed differently in the HPV16-positive cervical cancer group and HPV16-positive normal group (fold change ≥ 2). The results of qPCR showed that miR-148a-3p, miR-190a-5p, miR-199b-5p, and miR-655-3p levels significantly decreased in the cancer group compared with the normal group. Upon silencing of HPV16 E5 and E6/E7, miR-148a-3p levels increased in both cell lines. Silencing of E6/E7 in SiHa cells led to the increase in miR-199b-5p and miR-190a-5p levels. Three HPV16 oncoproteins (E5, E6, and E7) downregulate miR-148a-3p, while E6/E7 inhibit miR-199b-5p and miR-190a-5p expression in cervical carcinoma. The three microRNAs, miR-148a-3p, miR-199b-5p, and miR-190a-5p, may be novel diagnostic biomarkers for cervical cancer development in high-risk HPV-positive patients.

Clinicopathologic Significance of SATB1 and DJ-1 Proteins Expression in Cervical Carcinoma

Background: Special AT-rich sequence binding protein 1 (SATB1) and DJ-1 proteins play a crucial role in tumorigenesis and tumor progression in many human malignancies. Limited data is available in literature about their role in cervical carcinomas. Aims: The present study was designed to investigate the immunohistochemical expression of SATB1 and DJ-1 proteins in cervical carci­noma and their relationships to clinicopathologic variables. Material and Methods: Tissue sections from 100 cervical lesions distributed as 60 cases of cervical carcinoma, 30 cases of squamous intraepithelial lesion (SIL) and 10 cases with normal cervical tissue were evaluated for SATB1 and DJ-1 proteins expression by immunohistochemistry. Results: SATB1 expression was detected in 41.7% of cervical carcinomas versus 20% and 6.7% of HSIL and LSIL, respectively (p = 0.019). A significant positive correlation between SATB1 expression to lymph node metastasis (p = 0.004) and pTNM (p = 0.028) was noted. DJ-1 expression was detected in 68.3% versus 33.3% and 13.3% of HSIL and LSIL, respectively (p = 0.001). A significant positive association between DJ-1 expression and lymph node metastasis (p = 0.037) was noted. Normal cervical tissue was negative for SATB1 and DJ-1 expression. A significant positive association between SATB1 and DJ-1 immunoreactivity was detected in investigated cervical carcinomas (p = 0.027). Conclusions: SATB1 and DJ-1 are shown to be promising potential prognostic biomarkers in cervical carcinoma since their overexpression is correlated with advanced clinicopathologic variables including lymph node metastasis. SATB1 and DJ-1 can be promising therapeutic targets for cervical cancer.

Study on the methylation status of SPINT2 gene and its expression in cervical carcinoma.

Cervical cancer is one of the malignant tumors which seriously threaten the women health worldwide. SPINT2 is an endogenous inhibitor of hepatocyte growth factor activator and down regulated or even silenced in many human malignant tumors. This study was performed to explore the promoter methylation status of SPINT2 gene and the effect on its expression in cervical carcinoma. HPV-positive and -negative cervical cancer cell lines, 50 cases of cervical carcinoma tissues, and 20 cases of normal cervical tissues were used for this study. The methylation status of promoter and the first exon of SPINT2 gene were analyzed. The expression of SPINT2 was analyzed by qRT-PCR. HPV E6/E7 infection affects SPINT2 methylation rate in cell lines. SPINT2 methylation rate of HT-3E6/E7 was 8.8%, while the methylation rate of SPINT2 in HT-3 was 0%. In cervical tissues, the methylation rate of SPINT2 in cervical cancers was 54%, while the methylation rate of SPINT2 in normal cervical samples was 25%. As for cervical cancers, the methylation rate of SPINT2 gene was higher in grade 3 than those of grade 2. The expression of SPINT2 gene is regulated by its methylation status, and the methylation status of SPINT2 is altered by HPV infection. The aberrant methylation status of SPINT2 gene may play an important role in the development of cervical cancer.

MicroRNA-409 inhibits the proliferative ability of cervical carcinoma cells by regulating AKT.

To observe the microRNA-409-3p expression in cervical carcinoma and its effect on the growth and proliferative ability of cervical carcinoma cells. The microRNA-409-3p level in 62 cases of cervical carcinoma and 38 cases of normal cervical tissue was detected by qRT-PCR. The association between the microRNA-409-3p level and clinicopathological features of cervical carcinoma was investigated. Knockdown and overexpressed microRNA-409-3p in cervical carcinoma cells, HeLa and SiHa, were used to detect the cell cycle and the activity of cervical carcinoma cells. Subsequently, potentially target genes of microRNA-409-3p were predicted by bioinformatics website. Western Blot and luciferase assay were used to confirm their correlation. We observed a significant lower microRNA-409-3p level in cervical carcinoma tissues than that in normal cervical tissues. Significant correlation was found between the microRNA-409-3p level in patients with cervical carcinoma and the overall survival rate, tumor size and TNM stage (p<0.05), but correlations with age, pathological type and lymph node metastasis were not found (p>0.05). After silencing the expression of microRNA-409-3p in cervical carcinoma cells, the proliferative ability of cervical carcinoma cells was greatly promoted. In addition, microRNA-409-3p was targeting on protein kinase B (AKT) and had a negative correlation with AKT expression. The microRNA-409-3p level was lower in cervical carcinoma tissues, and was significantly affected the overall survival, tumor size and TNM staging in clinical patients. Low expression of microRNA-409-3p could promote the proliferative ability of cervical carcinoma cells through the target gene AKT.

Integrated analysis of chromosome copy number variation and gene expression in cervical carcinoma.

ObjectiveThis study was conducted to explore chromosomal copy number variations (CNV) and transcript expression and to examine pathways in cervical pathogenesis using genome-wide high resolution microarrays.MethodsGenome-wide chromosomal CNVs were investigated in 6 cervical cancer cell lines by Human Genome CGH Microarray Kit (4x44K). Gene expression profiles in cervical cancer cell lines, primary cervical carcinoma and normal cervical epithelium tissues were also studied using the Whole Human Genome Microarray Kit (4x44K).ResultsFifty common chromosomal CNVs were identified in the cervical cancer cell lines. Correlation analysis revealed that gene up-regulation or down-regulation is significantly correlated with genomic amplification (P=0.009) or deletion (P=0.006) events. Expression profiles were identified through cluster analysis. Gene annotation analysis pinpointed cell cycle pathways was significantly (P=1.15E-08) affected in cervical cancer. Common CNVs were associated with cervical cancer.ConclusionChromosomal CNVs may contribute to their transcript expression in cervical cancer.

NAC1 Regulates Somatic Cell Reprogramming by Controlling Zeb1 and E-cadherin Expression.

SummaryReprogramming somatic cells to induced pluripotent stem cells (iPSCs) is a long and inefficient process. A thorough understanding of the molecular mechanisms underlying reprogramming is paramount for efficient generation and safe application of iPSCs in medicine. While intensive efforts have been devoted to identifying reprogramming facilitators and barriers, a full repertoire of such factors, as well as their mechanistic actions, is poorly defined. Here, we report that NAC1, a pluripotency-associated factor and NANOG partner, is required for establishment of pluripotency during reprogramming. Mechanistically, NAC1 is essential for proper expression of E-cadherin by a dual regulatory mechanism: it facilitates NANOG binding to the E-cadherin promoter and fine-tunes its expression; most importantly, it downregulates the E-cadherin repressor ZEB1 directly via transcriptional repression and indirectly via post-transcriptional activation of the miR-200 miRNAs. Our study thus uncovers a previously unappreciated role for the pluripotency regulator NAC1 in promoting efficient somatic cell reprogramming.

Genetic and epigenetic alterations affecting PARK-2 expression in cervical neoplasm among North Indian patients.

The recent investigation on PARK-2, a putative tumor suppressor gene, has found that it has been altered in multiple human malignancies. However, the clinical impact of PARK-2 alteration in uterine cervix carcinoma has not yet been studied. Therefore, we aimed to examine mutations, promoter hypermethylation, and protein expression of PARK-2 among the North Indian patients and their association with clinical parameters to evaluate the implication of PARK-2 in the genesis of cervical cancer. A total of 168 patient samples were processed for mutational analysis by single-strand conformation polymorphism, sequencing, and further in silico analysis of the identified mutations. Promoter hypermethylation by methylation-specific polymerase chain reaction and expression of PARK-2 were performed using immunohistochemistry. Statistical correlation between molecular findings and the clinicopathological parameters was taken to figure out the meaningful outcome. As per our findings, 3.5% (6/168) tumors showed novel missense mutations in exon 11 of PARK-2. In silico analysis showed high structural deviations manifested by mutations, A398D and Y391N, in both mutant proteins as compared to wild type. Promoter hypermethylation was observed in total of 29% of (48/168) tumor samples. Furthermore, 46.43% tumors (78/168) exhibited loss of PARK-2 expression in cervical carcinoma. The loss of expression of PARK-2 when correlated with clinical parameters resulted in significant association with tumor stage (p = 0.002) and with histological grade (p = 0.025). However, only clinical stage remained significant after Bonferroni correction (p < 0.007). A trend was observed between PARK-2 promoter hypermethylation and its protein expression. Our study provided sufficient information and insight for investigation of PARK-2 and highlighted its role as a tumor suppressor gene in cervical cancer in North Indian population.

Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma.

Human leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial. The pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas. In squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P < 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 ± 13.0 vs 53.3 ± 30.5 months; P = 0.004) and disease-specific survival (226.45 ± 11.5 vs 75.8 ± 27.6 months; P = 0.002). Upregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors.

DJ-1 Expression in Cervical Carcinoma and its Effects on Cell Viability and Apoptosis.

BackgroundThis study aimed to investigate the expression of DJ-1 in cervical carcinoma and its effects on cell viability and apoptosis.Material/MethodsCervical carcinoma cell line Hela and 85 tissue samples, including 45 primary tumor biopsies, 30 para-carcinoma tissues, and 10 normal cervical tissues samples were used in this study. The expressions of DJ-1 in cervical carcinoma tissue, para-carcinoma tissue, and normal tissue samples were investigated by immunohistochemistry. DJ-1 expression in Hela cells was also investigated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. DJ-1 was interfered and transfected with siRNA, then cell viability and apoptosis were assayed by MTT and flow cytometry, respectively. Additionally, the expressions of phosphatase and tensin homolog (PTEN), AKT, and phospho-AKT (P-AKT) were detected.ResultsImmunohistochemistry results showed that DJ-1 was highly expressed in cervical carcinoma tissues. In Hela cells, the expression of DJ-1 was significantly higher than that in normal controls (P<0.05). When cells were treated with DJ-1 siRNA, the cell viability decreased significantly (P<0.05), and the percentage of apoptosis cells increased significantly (P<0.05). In addition, the expressions of PTEN and AKT were significantly higher in the DJ-1 siRNA treatment group than those in the control group (P<0.05). The expression of p-AKT was significantly lower in the DJ-1 siRNA treatment group than in the control group and the DJ-1 over-expression group (P<0.05).ConclusionsThe aberrant up-regulation of DJ-1 expression might be an important step in the pathogenesis of cervical carcinoma.