scholarly journals NUCKS nuclear elevated expression indicates progression and prognosis of ovarian cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (9) ◽  
pp. 101042831771463 ◽  
Author(s):  
Ce Shi ◽  
Ling Qin ◽  
Hongyu Gao ◽  
Lina Gu ◽  
Chang Yang ◽  
...  

NUCKS (nuclear, casein kinase, and cyclin-dependent kinase substrate) is implicated in the tumorigenesis of several human malignancies, but its role in ovarian cancer remains unknown. We aim to investigate NUCKS expression and its clinical significance in ovarian cancer. The messenger RNA expression of NUCKS was determined in normal and malignant ovarian tissues using quantitative polymerase chain reaction assay. Immunohistochemistry was applied to detect the status of NUCKS protein expression in 121 ovarian cancer tissues. NUCKS protein high expression was detected in 52 (43.0%) of 121 patients. NUCKS messenger RNA expression was gradually upregulated in non-metastatic ovarian cancers ( n = 20), metastatic ovarian cancers ( n = 20), and its matched metastatic lesions ( n = 20) in comparison with that in normal ovarian tissues ( n = 10; p < 0.05). Elevated expression of NUCKS in ovarian cancer was associated significantly with the Federation of Gynecology and Obstetrics stage ( p = 0.037), histological grade ( p = 0.003), residual disease ( p = 0.013), lymph node metastasis ( p = 0.002), response to chemotherapy ( p < 0.001), and recurrence ( p = 0.013). In the multivariate Cox analysis, NUCKS expression was an independent prognostic marker for overall survival and disease-free survival in ovarian cancer with p values of <0.001 for both. Especially, NUCKS overexpression had prognostic potential for overall survival and disease-free survival ( p < 0.001 for both) in advanced ovarian cancers and only for disease-free survival in early ovarian cancers ( p = 0.017). Our data suggest that NUCKS overexpression may contribute to progression and poor prognosis in ovarian cancer especially in advanced ovarian cancer.

2018 ◽  
Vol 28 (3) ◽  
pp. 459-465 ◽  
Author(s):  
Juliana A. Josahkian ◽  
Fabiano Pinto Saggioro ◽  
Thiago Vidotto ◽  
Henrique Torres Ventura ◽  
Francisco José Candido dos Reis ◽  
...  

ObjectiveRecently it has been demonstrated that constitutively activated signal transducer and activator of transcription 1 (STAT1) gene expression may act as a biomarker of ovarian cancer chemotherapy response. In this study, our objective was to validate the use of STAT1 immunohistochemistry as a prognostic biomarker for disease outcome using a cohort derived from Latin America.MethodsWe evaluated a cohort of Brazilian high-grade serous ovarian cancer, comprising 65 patients with outcome data covering more than 5 years to determine the prognostic and predictive value of STAT1 expression levels. High-grade serous ovarian cancer tumors were used to construct a tissue microarray. Exploratory analyses were conducted on clinical, histopathological, and STAT1 expression data that included descriptive statistics and Pearson correlative analyses. Survival curves for disease-free survival and overall survival were obtained by the Kaplan-Meier method, and the significance of homogeneity between the classes was assessed by log-rank statistics (Mantel-Cox).ResultsHigh expression of STAT1 in tumors was significantly associated with improved disease-free survival (P = 0.0256) and overall survival (P = 0.0193). Proportional hazards regression analysis showed STAT1 expression had an independent effect on both disease-free survival (P = 0.0358) and overall survival (P = 0.0469).ConclusionsThese findings from a Brazilian cohort of patients with ovarian cancer reinforce the association of high STAT1 expression with better response to chemotherapy, providing additional validation of this protein as both a prognostic and predictive biomarker. Collectively, these results together with other recently published studies increase the feasibility of using the STAT1 pathway for the development of novel immunomodulator drugs that could enhance response to treatment.


2018 ◽  
Vol 28 (4) ◽  
pp. 675-683 ◽  
Author(s):  
Kohshiro Nakao ◽  
Takashi Hirakawa ◽  
Hiroto Suwa ◽  
Kayoko Kogure ◽  
Sadatomo Ikeda ◽  
...  

ObjectiveThe ubiquitin C-terminal hydrolase L1 (UCHL1) plays a key role in tumor invasion and metastasis. Ubiquitin C-terminal hydrolase L1 is overexpressed in various cancers and reported to be correlated with a poor prognosis. The objective of this study was to determine the prognostic significance of UCHL1 in endometrial cancer.MethodsThe expression of UCHL1 in endometrial cancer was assessed using quantitative reverse transcription polymerase chain reaction and immunohistochemistry in 56 and 215 resected tumor specimens, respectively.ResultsThe 4-year survival rates of the high UCHL1 messenger RNA expression group and high UCHL1 protein expression group were 78% and 71%, respectively, compared with 96% and 95% for the low UCHL1 messenger RNA expression group and low UCHL1 protein expression group, respectively. Kaplan-Meier and log-rank tests indicated a significant correlation between expression of UCHL1 and disease-free survival and overall survival. Moreover, multivariate stepwise Cox proportional hazard regression model analysis showed that UCHL1 was a significant independent marker for predicting a poor disease-free survival and overall survival. In 43 patients with metastatic lesions, immunohistochemical analysis of metastatic lesions revealed that the recurrence rate and mortality rate were 62% and 41%, respectively, in 29 UCHL1-positive patients and 36% and 29%, respectively, in 14 UCHL1-negative patients.ConclusionsThe results of this study suggest that high UCHL1 expression is a strong marker of poor prognosis of endometrial cancer. Furthermore, we suggest that UCHL1 may be involved in the development of distant metastasis in endometrial cancer.


2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Anne Marszalek ◽  
Séverine Alran ◽  
Suzy Scholl ◽  
Virginie Fourchotte ◽  
Corinne Plancher ◽  
...  

Objectives. The purpose of this retrospective evaluation of advanced-stage ovarian cancer patients was to compare outcome with published findings from other centers and to discuss future options for the management of advanced ovarian carcinoma patients.Methods. A retrospective series of 340 patients with a mean age of 58 years (range: 17–88) treated for FIGO stage III and IV ovarian cancer between January 1985 and January 2005 was reviewed. All patients had primary cytoreductive surgery, without extensive bowel, peritoneal, or systematic lymph node resection, thereby allowing initiation of chemotherapy without delay. Chemotherapy consisted of cisplatin-based chemotherapy in combination with alkylating agents before 2000, whereas carboplatin and paclitaxel regimes were generally used after 1999-2000. Overall survival and disease-free survival were analyzed by the Kaplan-Meier method and the log-rank test.Results. With a mean followup of 101 months (range: 5 to 203), 280 events (recurrence or death) were observed and 245 patients (72%) had died. The mortality and morbidity related to surgery were low. The main prognostic factor for overall survival was postoperative residual disease (P<.0002), while the main prognostic factor for disease-free survival was histological tumor type (P<.0007). Multivariate analysis identified three significant risk factors: optimal surgery (RR=2.2for suboptimal surgery), menopausal status (RR=1.47for postmenopausal women), and presence of a taxane in the chemotherapy combination (RR=0.72).Conclusion. These results confirm that optimal surgery defined by an appropriate and comprehensive effort at upfront cytoreduction limits morbidity related to the surgical procedure and allows initiation of chemotherapy without any negative impact on survival. The impact of neoadjuvant chemotherapy to improve resectability while lowering the morbidity of the surgical procedure is discussed.


Author(s):  
Adarsh Dharmarajan ◽  
A. Remya ◽  
Aswathi Krishnan

Background: Assessment of CA-125 kinetics was commonly used as a tool for tumor response to chemotherapy in ovarian cancer patients. The study aimed to determine any logarithmic/linear relationship between pre-chemotherapy and pre-operative CA-125 levels in ovarian cancer.Methods: Total 52 patients who underwent neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery were included. CA-125 levels before starting chemotherapy, during chemotherapy and the preoperative value, with the date of measurement recorded. Cox’s proportional hazards regression was used to evaluate univariate and independent multivariable association with the effect of clinical, pathological and CA-125 kinetic parameters on outcome endpoints.  Results: The study couldn’t establish any relationship in logarithmic fall of CA-125 values among ovarian cancers as a result of neo-adjuvant chemotherapy. The disease-free survival among the patients was 12.2 months.Conclusions: There is an inverse relationship between serum CA-125 levels and survival in ovarian cancer. NACT resulted in adequate fall of CA-125 levels in most of the patients, but the rate of fall was not predictive of prognosis.


2019 ◽  
Vol 29 (9) ◽  
pp. 1405-1410
Author(s):  
Antonio Bandala-Jacques ◽  
Fabiola Estrada-Rivera ◽  
David Cantu ◽  
Diddier Prada ◽  
Gonzalo Montalvo-Esquivel ◽  
...  

BackgroundDysgerminomas are malignant ovarian germ-cell tumors that typically affect young women. Although these tumors have an excellent response to chemotherapy, surgery is an integral part of primary treatment.ObjectiveTo evaluate outcomes of initial cytoreduction in patients diagnosed with dysgerminomas.MethodsPatients who underwent primary cytoreductive surgery for ovarian dysgerminoma between January 1985 and December 2013 were identified and included in the study. A comparison was made between patients who underwent optimal versus sub-optimal cytoreduction. Descriptive, comparative statistics and odds ratios were used to establish an association. Survival curves were performed with the Kaplan-Meier method and compared using a log-rank test. A value of p<0.05 was used to establish a statistical difference.ResultsA total of 180 patients with a histologically confirmed dysgerminoma were included in the analysis. A subsection of 37 patients in stages III/IV were analyzed. The median age at diagnosis was 21 years (IQR 18–26). Histologically, 166 (92.2%) patients had pure dysgerminomas, whereas the rest had mixed histologies. The median tumor size was 18 (IQR 12–22) cm. In all stages, factors associated with optimal cytoreduction, were higher lactate dehydrogenase levels (OR=1.01; p=0.03), higher CA125 levels (OR=1.01; p=0.04), receiving adjuvant chemotherapy (OR=0.22; p<0.01), or undergoing treatment in a specialized institution (OR=12.68; p<0.01). Patients in stages III/IV, initially managed outside our institution were less likely to be taken for cytoreduction (OR=16.88; p=0.013). Other factors, including age (OR=1.02; p=0.39), pelvic lymph-node positivity (OR=2.24; p=0.36), pregnancy during follow-up (OR=0.91: p=0.80), or recurrence of disease (OR=1.93; p=0.23) were found to be similar in both groups. Overall survival was higher in optimally cytoreducted patients (100% vs 95.7%; p=0.032) including all stages, but not if considering only stages III/IV (100% vs 90%, p=0.186); disease-free survival was the same for both groups regardless of stage (94.3% vs 91.1%; p=0.36).ConclusionPatients with optimal surgeries were most likely to be treated in referral centers. Initial residual disease did not significantly alter recurrence, progression, disease-free survival, or overall survival.


2020 ◽  
Vol 66 (1) ◽  
pp. 61-66
Author(s):  
Millena Prata Jammal ◽  
Agrimaldo Martins Filho ◽  
Guilherme Henrique Bandeira ◽  
Beatriz Martins Tavares Murta ◽  
Eddie Fernando Candido Murta ◽  
...  

SUMMARY OBJECTIVE To relate disease-free survival and overall survival with type I and type II ovarian cancer and preoperative laboratory parameters biomarkers. METHODS A retrospective study was carried out based on the collection of data from medical records of patients with ovarian tumors. Kaplan-Mayer curves were drawn based on the statistical analysis of the data and were compared using the Log-rank test. RESULTS Disease-free survival in type I ovarian cancer was significantly higher than in type II (p=0.0013), as well as in those with normal levels of CA-125 (p=0.0243) and with a platelet-lymphocyte ratio (PLR) lower than 200 (p=0.0038). The overall survival of patients with type I ovarian cancer was significantly higher than in patients with type II, as well as in patients with normal CA-125 serum levels (p=0.0039) and those with a preoperative fasting glucose of less than 100 mg/dL. CONCLUSION CA-125 levels may predict greater overall and disease-free survival. PLR < 200 may suggest greater disease-free survival, whereas normal fasting glucose may suggest greater overall survival.


2020 ◽  
Vol 9 (12) ◽  
pp. 4105
Author(s):  
Marko Hojnik ◽  
Nataša Kenda Šuster ◽  
Špela Smrkolj ◽  
Snježana Frković Grazio ◽  
Ivan Verdenik ◽  
...  

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06−0.65, p = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12–0.88, p = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer.


2015 ◽  
Vol 25 (6) ◽  
pp. 993-999 ◽  
Author(s):  
Gregg Van de Putte ◽  
Jolien Oben ◽  
Leen Prenen ◽  
Jean Christophe Schobbens ◽  
Jos Vlasselaer ◽  
...  

IntroductionThe standard treatment of ovarian cancer is the combination of debulking surgery and chemotherapy. There is an ongoing discussion on which treatment is best: primary debulking surgery (PDS) or neoadjuvant chemotherapy with interval debulking (NACT-IDS). Even a large randomized trial has not settled this issue. We examined whether comparing a specified treatment protocol would not be a more logical approach to answer this type of discussions.MethodsA retrospective study of 142 consecutively treated patients according to a fixed protocol between 2000 and 2012 was conducted. Disease-free survival and overall survival were calculated by univariate and multivariate analyses for the whole group and for advanced stages separately. Specific differences between PDS and NACT-IDS were studied. Comparison of results from large databases was made.ResultsDisease-free survival and overall 5-year survival for the whole group were 35% and 50%. For the advanced stages, disease-free survival and overall 5-year survival were 14% and 36%, with a median disease-free and overall survival of 16 and 44 months. Of the 98 women with advanced ovarian carcinoma, 54% of operable patients underwent PDS and 44% underwent NACT-IDS. More patients in the PDS group were optimally (<1 cm) debulked: 80% vs 71%. There was no significant difference in survival between PDS or NACT-IDS. Optimally debulked patients had a significant better overall survival in multivariate analysis with a hazard ratio of 2.1.DiscussionOutcome of treatment according to a fixed protocol with a mixture of PDS and NACT-IDS was similar to results from large databases. We hypothesize that comparison of a specific strategy may yield more useful results than awaiting the perfect randomized trial.


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