Evaluation of the prognostic significance of human kallikrein 8 protein expression levels in advanced ovarian cancer by using automated quantitative protein analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5581-5581
Author(s):  
P. Kountourakis ◽  
A. Psyrri ◽  
A. Scorilas ◽  
S. Markakis ◽  
D. Kowalski ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Analysis ◽  
Protein Expression ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Protein Analysis ◽  
Free Survival ◽  
Expression Levels ◽  
Response To Chemotherapy

5581 Background: Kallikreins, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. Here, we sought to determine the prognostic value of kallikrein 8 (hkl8) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. Materials and Methods: A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of kallikrein 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Results: Mean follow-up time of the cohort was 34.35 months. One hundred twenty six of 150 cases had sufficient tissue for AQUA analysis. There was association between tumor mask hk8 protein expression levels and clinicopathological variables including grade (p=0.0011), residual disease (p=0.0063),clinical response to chemotherapy (p=0.0346). In univariate survival analysis there was a correlation between hk8 tumor mask expression and 5 years progression-free survival. Low hk8 expression correlated with better outcome (top vs. bottom quartile, p = 0.0319). In multivariate survival analysis, adjusting for well-characterized prognostic variables, tumor hkl8 expression level retained its prognostic significance for disease free survival (95%CI: 0.341–1.027, p=0.0468). Conclusions: Human Kallikrein 8 is an adverse prognostic factor in patients with ovarian cancer.The possibilities that hK8 may be suitable candidate as diagnostic, prognostic marker and therapeutic target merit further investigation. No significant financial relationships to disclose.

Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis

2009 ◽  
Vol 101 (03) ◽  
pp. 541-546 ◽  
Author(s):  
Andreas Scorilas ◽  
Sonia Markakis ◽  
Diane Kowalski ◽  
Robert L. Camp ◽  
Eleftherios P. Diamandis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Analysis ◽  
Protein Expression ◽  
Prognostic Significance ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Protein Analysis ◽  
Free Survival ◽  
Response To Chemotherapy

SummaryKallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8,hK8,KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p=0.0011), residual disease (p=0.0063) and clinical response to chemotherapy(p=0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p =0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p=0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341–1.027, p=0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.

scholarly journals Prognostic and predictive value of combined HE-4 and CA-125 biomarkers during chemotherapy in patients with epithelial ovarian cancer

2020 ◽  
Vol 35 (4) ◽  
pp. 20-27 ◽  
Author(s):  
Enrico Potenza ◽  
Giulia Parpinel ◽  
Maria E. Laudani ◽  
Chiara Macchi ◽  
Luca Fuso ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Predictive Value ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Ca 125 ◽  
Free Survival ◽  
The Third ◽  
Response To Chemotherapy

Introduction: At present there is no predictive value univocally associated with the success of chemotherapy. Biomarkers produced by ovarian cancer (HE4 and Ca125) could have a good prognostic significance. The aim of this study is to prove the ability of biomarkers to identify patients with the highest risk of non-optimal response during the chemotherapy, and to predict which patients will most likely develop recurrence of disease. Methods: We analyzed 78 patients with epithelial ovarian cancers who underwent surgery in the biennium 2016–2017. All the patients underwent chemotherapy after surgery or interval debulking surgery following neoadjuvant therapy. Serum levels of HE4 and Ca125 were measured at diagnosis and at each cycle of chemotherapy. We established the degree of response to the treatment by computed tomography scan, and the patients were followed up (median: 10 months). The parameters of progression-free survival and disease-free survival were related to serum levels of biomarkers. Results: Both CA125 and HE4 values became negative at the fourth cycle in the patients with good response to chemotherapy. HE4 increased earlier than Ca125. The parameters that best correlated with a long progression-free survival were: negativization of the marker after the third cycle of chemotherapy (HE4: odds ratio (OR) 5.5; Ca125: OR 9.1) and biomarker serum levels lower than the mean value in the affected population at the time of diagnosis (HE4: OR 3.4; Ca125: OR 3.7). Conclusions: We can conclude that the monitoring of HE4 and Ca125 during chemotherapy, especially at the third cycle, is recommended, because their variation is a good prognostic factor.

scholarly journals Dynamic analysis of serum Ca-125 levels during neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer: a retrospective study

2020 ◽  
Vol 10 (1) ◽  
pp. 88
Author(s):  
Adarsh Dharmarajan ◽  
A. Remya ◽  
Aswathi Krishnan
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Proportional Hazards ◽  
Disease Free Survival ◽  
Ca 125 ◽  
Free Survival ◽  
Proportional Hazards Regression ◽  
Response To Chemotherapy ◽  
Neo Adjuvant Chemotherapy ◽  
Disease Free

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.

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 ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Messenger Rna ◽  
Disease Free Survival ◽  
Rna Expression ◽  
Free Survival ◽  
Ovarian Cancers ◽  
Response To Chemotherapy ◽  
Elevated Expression ◽  
Disease Free

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.

Assessment of phosphatidylinositol-3 kinase (PI3K) as a prognostic marker in head and neck squamous cell carcinoma (HNSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17028-e17028
Author(s):  
E. Pectasides ◽  
G. Founztilas ◽  
C. Sasaki ◽  
B. Burtness ◽  
A. Psyrri
Keyword(s):  
Survival Analysis ◽  
Protein Expression ◽  
Statistical Significance ◽  
External Beam Radiotherapy ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Rank Test ◽  
Phosphatidylinositol 3 Kinase ◽  
Expression Levels ◽  
Phosphatidylinositol 3

e17028 Background: Deregulated signaling through phosphatidylinositol 3’-kinase (PI3K) pathway is common in several cancers, including HNSCC. In the present study we investigated the relationship between PI3K protein expression and outcome in patients with HNSCC. Methods: A tissue microarray composed of 122 specimens from primary HNSCC cases treated with either external beam radiotherapy (EBRT) or gross total surgical resection and EBRT was constructed. Protein expression levels for PI3K were analyzed using an immunofluorescence-based assay that provides an automated, quantitative analysis of expression within subcellular compartments (AQUA). Primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for assessing statistical significance. Results: Mean follow-up time for the cohort was 40 months. Ninety-seven of 122 cases had sufficient tissue for analysis and continuous AQUA scores were divided into quartiles. Survival analysis showed that patients in the top and bottom quartile had a significantly shorter OS (p = 0.015). In multivariable analysis, adjusting for well-characterized prognostic variables, PI3K expression retained its prognostic significance. Conclusions: Our study suggests that in situ quantitative measurement of PI3K stratifies HNSCC into four expression levels where both low and high levels are associated with a worse outcome. We speculate that transmission of growth factor receptor signals that promote tumor aggression in these low expressers may occur via PI3K/Akt independent mechanisms. It is possible that activation of such alternate pathways in some tumors results in the down-regulation of PI3K expression via a feedback mechanism, producing aggressive tumors bearing a PI3K-low phenotype. No significant financial relationships to disclose.

scholarly journals AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas

2020 ◽  
Vol 9 (12) ◽  
pp. 4105
Author(s):  
Marko Hojnik ◽  
Nataša Kenda Šuster ◽  
Špela Smrkolj ◽  
Snježana Frković Grazio ◽  
Ivan Verdenik ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Confidence Interval ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Developed Countries ◽  
Hazard Ratio ◽  
Free Survival ◽  
Response To Chemotherapy ◽  
Disease Free

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.

scholarly journals Bioinformatics analysis of FOLR1 expression, functional enrichment, related signaling pathways and relationship with prognosis in ovarian cancer

Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 46-54
Author(s):  
Yan Wang ◽  
Xiao Li ◽  
Pengpeng Qu
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Clustering Coefficient ◽  
Ppi Network ◽  
Free Survival ◽  
Expression Levels ◽  
Mrna Expression Levels

AbstractObjective To investigate folate-receptor 1 (FOLR1) expression in ovarian cancer and its association with patient prognosis.Methods TCGA and Oncomine databases were used to collect data about FOLR1 mRNA expression in multiple carcinomas. FOLR1 mRNA expression levels in ovarian cancer samples and corresponding adjacent normal ovary tissue were compared. A protein-protein interaction (PPI) network was constructed using the STRING database of FOLR1 and relevant genes. The overall survival (OS) and progression free survival (PFS) rates of ovarian cancer patients in high- and low- FOLR1 expression groups were compared by log-rank test. Sixty-six ovarian epithelial carcinoma samples were included in the study, and tumor specimens of the 66 cases were tested for FOLR1 protein expression by an immunohistochemistry assay.ResultsFOLR1 mRNA was significantly elevated in ovarian cancer compared to other carcinomas. FOLR1 mRNA expression levels were significantly higher in tumor tissues than in the corresponding normal tissues (P<0.05) of ovarian cancer patients. The PPI network indicated that the local clustering coefficient was 0.898, indicating that the PPI network was enriched significantly (P<0.05). The median PFS values were 22.39 and 19.00 months for lowand high-FOLR1 expression groups, respectively, with significant statistical difference between the two (HR=1.26, 95%CI:1.09-1.45, P<0.05). FOLR1 protein expression was correlated with tumor differentiation (P<0.05) in ovarian cancer patients. However, its levels were not correlated with patient age, tumor diameter, lymph node metastasis or FIGO stage (P>0.05).ConclusionFOLR1 is upregulated in epithelial ovarian cancer, and its expression is correlated with patients’ progression free survival, making it a valuable biomarker for prognosis.

Increased STAT1 Expression in High Grade Serous Ovarian Cancer Is Associated With a Better Outcome

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 ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Independent Effect ◽  
Chemotherapy Response ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Free Survival ◽  
Response To Chemotherapy ◽  
Disease Free

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.

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