scholarly journals Analysis of CCT7 Expression and Its Clinical Significance in Endometrial Cancer

2020 ◽  
Author(s):  
Liwen Wang ◽  
Wei Zhou ◽  
Hui Li ◽  
Hui Yang ◽  
Nianchun Shan

Abstract Objective: Endometrial cancer (EC) is a common gynecologic malignancy; myometrial invasion (MI) is a typical approach of EC spreads and an important index to assess tumor metastasis and outcome of EC patients. CCT7 is a member of the TCP1 chaperone family, involved in cytoskeletal protein folding and unfolding. In this study, the role of CCT7 in EC development was investigated. Methods: Clinical data for 87 EC cases and expression of CCT7 were analyzed. CCT7 was knocked out using siRNA- CCT7 in Ishikawa and RL95-2 cells, and their function about proliferation, apoptosis and invasion were further tested. Bioinformatics methods were used to predict the potential pathways of CCT7 in EC development. Results: The rates of CCT7-positive cells in EC and adjacent normal endometrium tissues had significant difference (67.8% vs. 51.4%, p = 0.035), and the expression rate increased from low to high pathological stage (39.7% in the I/II stage, 71.4% in the III/IV stage, p = 0.029). Similar change was found in protein level. CCT7 expression differed significantly between the deep MI group (>1/2) and the superficial MI group (≤1/2) (P = 0.039). However, there were no differences with respect to age, pathological type and histological grade. CCT7 suppression induced a function-loss in in both Ishikawa and RL95-2 cells. Bioinformatics analysis demonstrated that EC patients with lower level CCT7 expression had better Overall survival (p= 0.0081). GO enrichment indicated that “RNA binding”, “Mitochondrion”, “Translation”, and “Spliceosome” were most significantly enriched potential pathways. Five hub genes, PSMA5, PSMD14, SNRPB, SNRPG and TXNL4 A, were all significantly upregulated in EC and had positive correlation with CCT7. Conclusions: CCT7 may be involved in EC development by excessively activating tumor cell function to promote MI or distant/nodal metastasis, which definitely impaired the prognosis of EC patients.

Author(s):  
Liwen Wang ◽  
Wei Zhou ◽  
Hui Li ◽  
Hui Yang ◽  
Nianchun Shan

Abstract Background: Endometrial cancer (EC) is a common gynecologic malignancy; myometrial invasion (MI) is a typical approach of EC spreads and an important index to assess tumor metastasis and outcome of EC patients. CCT7 is a member of the TCP1 chaperone family, involved in cytoskeletal protein folding and unfolding. In this study, the role of CCT7 in EC development was investigated. Methods: Clinical data for 87 EC cases and expression of CCT7 were analyzed. CCT7 was knocked out using siRNA-CCT7 in Ishikawa and RL95-2 cells, and their function about proliferation, apoptosis and invasion were further tested. Bioinformatics methods were used to predict the potential pathways of CCT7 in EC development.Results: The rates of CCT7-positive cells in EC and adjacent normal endometrium tissues had significant difference (67.8% vs. 51.4%, p = 0.035), and the expression rate increased from low to high pathological stage (39.7% in the I/II stage, 71.4% in the III/IV stage, p = 0.029). Similar change was found in protein level. CCT7 expression differed significantly between the deep MI group (>1/2) and the superficial MI group (≤1/2) (P = 0.039). However, there were no differences with respect to age, pathological type and histological grade. CCT7 suppression induced a function-loss in in both Ishikawa and RL95-2 cells. Bioinformatics analysis demonstrated that EC patients with lower level CCT7 expression had better Overall survival (p= 0.0081). GO enrichment indicated that “RNA binding”, “Mitochondrion”, “Translation”, and “Spliceosome” were most significantly enriched potential pathways. Five hub genes, PSMA5, PSMD14, SNRPB, SNRPG and TXNL4A, were all significantly upregulated in EC and had positive correlation with CCT7.Conclusions: CCT7 may be involved in EC development by excessively activating tumor cell function to promote MI or distant/nodal metastasis, which definitely impaired the prognosis of EC patients.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao Li ◽  
Yiping Gao ◽  
Mingzi Tan ◽  
Huiyu Zhuang ◽  
Jian Gao ◽  
...  

The main aims of this study were to determine the expression of human epididymis protein 4 (HE4) in endometrial cancer and to explore the relationships between HE4 expression, clinicopathological parameters, and prognosis. Immunohistochemistry was used to detect HE4 expression in 102 cases of endometrial cancer, 30 cases of endometrial atypical hyperplasia, and 20 cases of normal endometrium. The positive expression rate of HE4 in endometrial carcinoma was 84.62%, significantly higher than 66.67% in atypical hyperplasia (P<0.05) and 15.00% in normal endometrium (P<0.0.01). With the exception of stage II, HE4 expression in endometrial cancer showed an increasing tendency with increased clinical stage (P<0.05). The positive expression rate of HE4 increased with a decrease in the degree of differentiation. A statistically significant difference was observed between the highly differentiated group and the poorly differentiated group (P<0.05). Mortality in endometrial cancer patients with high HE4 expression was significantly higher than that in patients with low HE4 expression (P<0.05). Endometrial cancer patients with high HE4 expression have a poor prognosis.


2017 ◽  
Vol 27 (4) ◽  
pp. 748-753 ◽  
Author(s):  
Alper Karalok ◽  
Taner Turan ◽  
Derman Basaran ◽  
Osman Turkmen ◽  
Gunsu Comert Kimyon ◽  
...  

ObjectiveThe aim of this study was to evaluate the effectiveness of histological grade, depth of myometrial invasion, and tumor size to identify lymph node metastasis (LNM) in patients with endometrioid endometrial cancer (EC).MethodsA retrospective computerized database search was performed to identify patients who underwent comprehensive surgical staging for EC between January 1993 and December 2015. The inclusion criterion was endometrioid type EC limited to the uterine corpus. The associations between LNM and surgicopathological factors were evaluated by univariate and multivariate analyses.ResultsIn total, 368 patients were included. Fifty-five patients (14.9%) had LNM. Median tumor sizes were 4.5 cm (range, 0.7–13 cm) and 3.5 cm (range, 0.4–33.5 cm) in patients with and without LNM, respectively (P = 0.005). No LMN was detected in patients without myometrial invasion, whereas nodal spread was observed in 7.7% of patients with superficial myometrial invasion and in 22.6% of patients with deep myometrial invasion (P < 0.0001). Lymph node metastasis tended to be more frequent in patients with grade 3 disease compared with those with grade 1 or 2 disease (P = 0.131).ConclusionsThe risk of lymph node involvement was 30%, even in patients with the highest-risk uterine factors, that is, those who had tumors of greater than 2 cm, deep myometrial invasion, and grade 3 disease, indicating that 70% of these patients underwent unnecessary lymphatic dissection. A precise balance must be achieved between the desire to prevent unnecessary lymphadenectomy and the ability to diagnose LNM.


2010 ◽  
Vol 20 (5) ◽  
pp. 745-750 ◽  
Author(s):  
Fan-ling Meng ◽  
Ming-zhu Yin ◽  
Hong-tao Song ◽  
Hua Yang ◽  
Ge Lou ◽  
...  

Background:Lysosomal protein transmembrane 4 β-35 (LAPTM4B-35), a novel oncoprotein that belongs to the mammalian 4-tetratransmembrane spanning protein superfamily, has been implicated in oncogenesis and cancer progression in several solid malignances. However, the expression of LAPTM4B-35 and its role in endometrial cancer progression remain unknown.Materials and Methods:We investigated the expression of the LAPTM4B-35 protein by immunohistochemistry in 30 normal endometrium specimens and 165 endometrial carcinomas and analyzed its correlation with various clinicopathologic features, including patient outcome.Results:LAPTM4B-35 immunoreactivity was overexpressed in endometrial carcinoma cases compared with normal endometrium (P < 0.001). High LAPTM4B-35 expression was found in 117 (70.91%) of these 165 carcinomas and was positively correlated with the International Federation of Gynecology and Obstetrics stage, histological grade, depth of myometrial invasion, lymph node metastasis, lymph vascular space involvement, and recurrence, but not with age and histological type. Patients with high LAPTM4B-35 expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of LAPTM4B-35 (P = 0.001 and P = 0.002, respectively). Multivariate analysis showed that high LAPTM4B-35 expression was an independent prognostic factor for both overall survival and disease-free survival of patients with endometrial carcinoma (both P = 0.005).Conclusions:These results showed that high LAPTM4B-35 expression was associated with progression and prognosis of endometrial carcinoma.


Author(s):  
Anu Sarah Easo ◽  
Rajeev Anand ◽  
Mini Issac

Background: To determine whether diffusion-weighted imaging (DWI) with measurement of apparent diffusion coefficient (ADC) will help in differentiating endometrial cancer from normal endometrium and to determine whether the grades of endometrial cancer will show significant difference in ADC values.Methods: This is a retrospective study done in MOSC medical college hospital Kolencherry. on patients on whom preoperative MRI was done before hysterectomy. Cases from July 2017 to March 2021 were included. Study cases included 40 females with pathologically confirmed endometrial cancer and 30 females with pathologically proven normal endometrium in cases of uterine leiomyoma and cervical cancer. The exclusion criteria for the study were patients with endometrial cancer in whom surgery was not done within 2 weeks of MRI, patients who were treated with chemotherapy or radiotherapy before surgery, patients who had hydrometra or pyometra.Results: The mean ADC value (10−3 mm2/second) of endometrial cancer was 0.77±0.04, which was significantly lower (p<0.05) than that of normal endometrium (1.323±0.05). The ADC values of different grades of endometrial cancers did not show any statistically significant difference (p>0.05).Conclusions: Our study showed that ADC measurement can differentiate between normal endometrium and endometrial cancer. The ADC values of different grades of endometrial cancers did not show any statistically significant difference.  


2020 ◽  
Author(s):  
Pampapati Veena ◽  
Rajalakshmi Ilango ◽  
Jayalakshmi Durairaj

AbstractObjectiveThe role of lymphadenectomy in early stage endometrial cancer is controversial as it is associated with intra-operative complications and its therapeutic benefit is not established. Prediction of lymph nodal metastasis so as to perform selective lymph node dissection is desirable. This study was conducted to study grade of the tumor obtained by endometrial biopsy specimen and depth of myometrial invasion assessed by imaging pre-operatively as predictors of lymph nodal metastasis in early endometrial cancers.MethodsOur study was a cross sectional study done in a tertiary care center in south India, where 100 patients were studied from August 2016 to May 2018. After Ethical Committee clearance, all patients who were diagnosed with early endometrial cancer and who underwent surgery in our hospital were included in the study after getting informed consent. Pre-operative tumor grade and depth of myometrial invasion were studied as predictors of lymph nodal metastasis. They were also correlated with post-operative grade and myometrial invasion.ResultsThe present study recruited 100 women of which 3 cases were excluded because of non-endometrioid histology. The incidence of positive lymph node metastasis in our study was 18.6%. Both pre-operative tumor grade and depth of myometrial invasion were not significantly associated with lymph node metastasis. There was significant variation between pre-operative and post-operative tumor grade and depth of myometrial invasion. Among post-operative histopathological factors, only lymphovascular space invasion was found to be significantly associated with lymph node metastasis.ConclusionIn our study, neither pre-operative nor post-operative grade of the tumor and depth of myometrial invasion were significantly associated with lymph node metastasis. There was considerable variation between pre-op and post-op grade of the tumor making pre-op grade an unreliable factor in predicting lymph node metastasis in endometrial cancer. Among post-operative histopathological factors, only lymphovascular space invasion was found to be significantly associated with lymph node metastasis.Key messageConsiderable variation between pre-op and post-op grade of the tumor makes pre-op grade an unreliable factor in predicting lymph node metastasis in endometrial cancer


2006 ◽  
Vol 16 (3) ◽  
pp. 1401-1406 ◽  
Author(s):  
J. Kodama ◽  
T. Kusumoto ◽  
N. Seki ◽  
T. Matsuo ◽  
Y. Ojima ◽  
...  

The aim of this study was to investigate the relationship between heparanase expression and prognostic factors in endometrial cancer, as well as the relationship between heparanase expression during phases of the normal endometrial cycle. Immunohistochemical analysis of 166 endometrial cancers and 34 normal endometria in various phases of growth was performed. The heparanase expression in the late-proliferative phase of normal endometria was found to be significantly higher than in either the early-proliferative or the secretory phases (P = .012 and P = .044, respectively). Heparanase expression was also significantly higher in endometrial cancer patients with tumors of an advanced FIGO stage (P = .0003) and high FIGO grade (P = .004) and with cancers showing either deep myometrial invasion (P = .023), lymph node metastasis (P = .006), lymphvascular space involvement (P = .048), or positive peritoneal cytology (P = .010). The disease-free and overall survival rates of patients with intense heparanase expression were significantly lower than those of patients with absent or moderate heparanase expression (P = .004 and P = .002, respectively). Heparanase may participate in normal endometrial remodeling and can serve as an indicator of the aggressive potential and poor prognosis of endometrial cancers.


2017 ◽  
Vol 27 (6) ◽  
pp. 1206-1215 ◽  
Author(s):  
Wei Jiang ◽  
Jun Chen ◽  
Xiang Tao ◽  
Feifei Huang ◽  
Menghan Zhu ◽  
...  

ObjectiveLimited data have been obtained in regard to pulmonary metastasis (PM) in patients with stage I endometrial cancer. The aims of the study were (1) to present the clinical and pathological characteristics of patients with PM in the setting of stage I endometrioid-type endometrial cancer (EEC) and (2) to define possible factors that may be used to predict PM.MethodsSix hundred thirty patients with stage I EEC, including 12 with PM, 19 with extra-PM (EPM), and 599 with no recurrence, were observed. Paired samples of primary and metastatic tumors from a patient were used for exome sequencing to identify potential gene mutations associated with PM.ResultsThere was no significant difference in the age, Ki-67, lymphatic vascular space invasion, and grade 3 among the 3 groups (P > 0.05). More squamous epithelial differentiation was observed in PM (7/12), as compared with patients with EPM (1/19) (P < 0.05) and no recurrence (20/599) (P < 0.05). The tumor size of the patients with PM was bigger than that of nonrecurrent patients (29.8 ± 16.6 vs 18.5 ± 16.3 mm, P < 0.05). More percentage of patients with deep myometrial invasion (IB) were found in PM (6/12) (P < 0.05) as compared with patients with EPM (3/19) (P < 0.05) and no recurrence (76/599). CDH10, ARID1A, and EMT-associated gene mutations were identified in metastatic tumor tissue but not in primary tumors from a patient with EEC and lung metastases.ConclusionsSquamous epithelial differentiation, large tumor size, and deep myometrial invasion might be risk factors for PM in patients with stage I EEC. CDH10, ARID1A, and EMT-associated gene mutation may promote the initiation of lung recurrence. However, further studies are needed to determine the precise mechanisms associated with lung metastasis in these patients.


2020 ◽  
Vol 61 (9) ◽  
pp. 1277-1286
Author(s):  
Juan Armando Reyes-Pérez ◽  
Yolanda Villaseñor-Navarro ◽  
Mayra Evelia Jiménez de los Santos ◽  
Irlanda Pacheco-Bravo ◽  
Maricela Calle-Loja ◽  
...  

Background Diffusion-weighted magnetic resonance imaging (DW-MRI) with apparent diffusion coefficient (ADC) measurement provides additional information about tumor microstructure with potential relevance for staging and predicting aggressive disease in patients with endometrial cancer (EC). Purpose To determine whether ADC values in EC diverge according to the tumor’s histologic grade and myometrial invasion depth. Material and Methods A sample of 48 pathologically confirmed cases of EC were reviewed retrospectively. The sample was distributed as follows: G1 (n = 9); G2 (n = 18); G3 (n = 21); with myometrial invasion <50% (n = 31); and with myometrial invasion ≥50% (n = 17). DW images were performed at 3.0T with b factors of 0–1000/mm2. The region of interest (ROI) was defined within the tumor with T1-weighted and T2-weighted imaging and copied manually to an ADC map. The tumor’s grade and myometrial invasion’s depth were determined by postoperative histopathological tests. Results The means of ADCmin and ADCmean values were significantly lower for patients with G2 and G3 endometrial tumors than G1. The same tendency was observed in myometrial invasion, as both ADCmin and ADCmean values were lower for patients with deep than for those with superficial myometrial invasion. The cut-off values of the ADCmin and ADCmean that predicted high-grade tumors were 0.69 × 10−3 mm2/s and 0.82 × 10−3 mm2/s, respectively, while those for myometrial infiltration were 0.70 × 10−3 mm2/s (ADCmin) and 0.88 × 10−3 mm2/s (ADCmean). Conclusion ADCmin and ADCmean values correlated with histologic tumor grade and myometrial invasion depth; therefore, it is suggested that ADC on MRI may be a useful indicator to predict malignancy of ECs.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Hiromitsu Yabushita ◽  
Keita Iwasaki ◽  
Kouhei Kanyama ◽  
Yukihiko Obayashi ◽  
Lisheng Zhuo ◽  
...  

The role of hyaluronan (HA), serum-derived HA-associated protein (SHAP)-HA complex and hyaluronan synthase (HAS) in endometrial carcinomas was investigated. The relationship of metalloproteinase (MMP) and its inhibitor (TIMP) with HA and the SHAP-HA complex was also examined. The expression of HAS1 was related to the depth of myometrial invasion and lymph-vascular space involvement. The serum levels of HA, SHAP-HA complex, MMP-9, and TIMP-1 were increased in related with the depth of myometrial invasion, histological grade and lymph-vascular space involvement. They were also higher in the HAS1-positive group compared to -negative group. The serum concentrations of HA and SHAP-HA complex had a significant correlation with the MMP-9 and TIMP-1. The patients with elevated SHAP-HA complex had the shorter disease-free survival. The multivariate analysis revealed that the SHAP-HA complex was the independent variable for disease-free survival of endometrial cancer patients. In conclusion, the elevation of serum SHAP-HA complex depended on the HAS1 expression and the SHAP-HA complex is a useful marker to predict disease recurrence in endometrial cancer patients. The SHAP-HA complex may promote the lymph-vascular space involvement and the synthesis and activation of MMP-9 and TIMP-1 in the progression of endometrial cancer.


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