High Expression of Ubiquitin C-terminal Hydrolase L1 Is Associated With Poor Prognosis in Endometrial Cancer Patients

2018 ◽  
Vol 28 (4) ◽  
pp. 675-683 ◽  
Author(s):  
Kohshiro Nakao ◽  
Takashi Hirakawa ◽  
Hiroto Suwa ◽  
Kayoko Kogure ◽  
Sadatomo Ikeda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Protein Expression ◽  
Messenger Rna ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Rna Expression ◽  
Free Survival ◽  
Metastatic Lesions ◽  
Disease Free

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.

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.

scholarly journals Prognostic implications of programmed death ligand 1 expression in resected lung adenocarcinoma: a systematic review and meta-analysis

2020 ◽  
Vol 58 (5) ◽  
pp. 888-898
Author(s):  
Donglai Chen ◽  
Yiming Mao ◽  
Qifeng Ding ◽  
Wei Wang ◽  
Feng Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Lung Adenocarcinoma ◽  
Messenger Rna ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
L1 Protein ◽  
Disease Free

Abstract OBJECTIVES Conflicting results have been reported about the prognostic value of programmed death ligand 1 (PD-L1) protein and gene expression in lung adenocarcinoma. METHODS We performed a comprehensive online search to explore the association between PD-L1 expression (protein and messenger RNA) and overall survival (OS) or disease-free survival. Outcomes also included pooled rates of high PD-L1 protein expression in different cell types, per threshold used and per antibody used. A pooled gene expression analysis was also performed on 3 transcriptomic data sets that were obtained from The Cancer Genome Atlas database and the Gene Expression Omnibus database. RESULTS A total of 6488 patients from 25 studies were included. The pooled results suggested that high PD-L1 expression was associated with shorter OS [hazard ratio (HR) 1.57; P &lt; 0.001] and disease-free survival (HR 1.341; P = 0.037) in the overall population. The overall pooled rate of high PD-L1 protein expression was 29% (95% confidence interval 23–34%) in tumour cells. In subgroup analysis, high PD-L1 protein expression in tumour cells predicted worse OS and disease-free survival. A pooled analysis of The Cancer Genome Atlas and Gene Expression Omnibus data sets revealed that higher levels of PD-L1 messenger RNA predicted poorer OS in the entire population. CONCLUSIONS This study is, to our knowledge, the largest pooled analysis on the subject to shed light on the high expression rate of PD-L1 and the prognostic value of high PD-L1 expression in resected lung adenocarcinomas. PD-L1 gene expression is a promising prognostic factor for patients with surgically resected lung adenocarcinoma. Standardization of staining should be underscored prior to routine implementation.

scholarly journals Prospective Cohort Study of Pre- and Postdiagnosis Physical Activity and Endometrial Cancer Survival

2020 ◽  
Vol 38 (34) ◽  
pp. 4107-4117
Author(s):  
Christine M. Friedenreich ◽  
Linda S. Cook ◽  
Qinggang Wang ◽  
Renée L. Kokts-Porietis ◽  
Jessica McNeil ◽  
...  
Keyword(s):  
Physical Activity ◽  
Overall Survival ◽  
Endometrial Cancer ◽  
Cohort Study ◽  
Disease Free Survival ◽  
Activity Levels ◽  
Recreational Physical Activity ◽  
Free Survival ◽  
Physical Activity Levels ◽  
Disease Free

PURPOSE The aim of this study was to evaluate associations between pre- and postdiagnosis physical activity and survival in survivors of endometrial cancer by physical activity domain, intensity, dose (metabolic-equivalent task [MET]-hours/week/year), and change from pre- to postdiagnosis. METHODS We conducted a prospective cohort study in Alberta, Canada, of 425 women who were diagnosed with histologically confirmed invasive endometrial cancer between 2002 and 2006 and observed to 2019. The interviewer-administered Lifetime Total Physical Activity Questionnaire recorded prediagnosis (assessed at a median of 4.4 months after diagnosis) and postdiagnosis physical activity (assessed at a median of 3.4 years after diagnosis). Associations between physical activity and overall and disease-free survival were assessed using Cox proportional hazards models adjusted for age, stage, grade, treatments, body mass index, menopausal status, hormone therapy use, family history of cancer, and comorbidities. RESULTS After a median follow-up of 14.5 years, there were 60 deaths, including 18 endometrial cancer deaths, and 80 disease-free survival events. Higher prediagnosis recreational physical activity was statistically significantly associated with improved disease-free survival (> 14 v ≤ 8 MET-hours/week/year; hazard ratio [HR], 0.54; 95% CI, 0.30 to 0.96; Ptrend = .04), but not overall survival (HR, 0.56; 95% CI, 0.29 to 1.07; Ptrend = .06). Higher postdiagnosis recreational physical activity (> 13 v ≤ 5 MET-hours/week/year) was strongly associated with both improved disease-free survival (HR, 0.33; 95% CI, 0.17 to 0.64; Ptrend = .001) and overall survival (HR, 0.33; 95% CI, 0.15 to 0.75; Ptrend = .007). Participants who maintained high recreational physical activity levels from pre- to postdiagnosis also had improved disease-free survival (HR, 0.35; 95% CI, 0.18 to 0.69) and overall survival (HR, 0.43; 95% CI, 0.20 to 0.94) compared with those who maintained low physical activity levels. CONCLUSION Recreational physical activity, especially postdiagnosis, is associated with improved survival in survivors of endometrial cancer.

scholarly journals Automated Quantification of CD44, c-MET, EGFR, MTOR, and GLUT1 Expression in Head and Neck Squamous Cell Carcinoma: The Impact of p16 Status and Response to Chemoradiation

2020 ◽  
pp. 1-10
Author(s):  
George Wilson ◽  
Jessica D. Arden ◽  
Thomas J. Quinn ◽  
Thomas G. Wilson ◽  
Alaa Hanna ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Locoregional Control ◽  
Free Survival ◽  
Automated Quantification ◽  
Control Disease ◽  
Disease Free

This study assessed automated quantification of CD44, c-MET, MTOR, EGFR, and GLUT1 protein expression in a tissue microarray of 109 Stage II-IV p16 positive and negative head and neck squamous cell carcinomas (HNSCC) treated with definitive chemoradiation. Immunohistochemistry-based protein expression was quantified in an automated manner using digitally scanned images processed with Definiens Tissue Studio software to generate a histologic score (H-score, range 0-300) which was normalized for each biomarker. Biomarker expression levels were correlated with one another and with p16 status. Effects of biomarker and p16 status on locoregional control, disease-free survival, and overall survival were analyzed using Kaplan Meier and Cox proportional hazard modelling. There was a significant negative correlation between CD44 and p16 expression and significant positive correlations between CD44 and MTOR, CD44 and GLUT1, c-MET and MTOR, and MTOR and GLUT1. When patients were stratified by p16 status, the significant positive correlation between CD44 expression and MTOR remained for both the p16 positive and negative subsets, while correlations between CD44 and GLUT1 and c-MET and MTOR were seen in the p16 negative subset only. A significant correlation between MTOR and GLUT was seen overall and for the p16 positive subset. When the effects of biomarker expression on clinical endpoints were examined, histologic scores below the defined cut-points for CD44 and c-MET were each associated with improved locoregional control. Higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with inferior disease-free and overall survival. On multivariable analysis, p16 positivity remained independently associated with improved locoregional control, disease-free survival, and overall survival, high CD44 remained independently associated with inferior locoregional control, disease-free survival, and overall survival, and EGFR with inferior disease-free and overall survival. In conclusion, the use of an automated system to quantify IHC expression allowed objective correlation between biomarkers and stratification of patients, revealing that higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with poorer disease-free and overall survival.

Role of adjuvant therapy in stage IIIC2 endometrial cancer

2020 ◽  
Vol 30 (8) ◽  
pp. 1169-1176
Author(s):  
Giorgio Bogani ◽  
Serena Cappuccio ◽  
Jvan Casarin ◽  
Deepa Maheswari M Narasimhulu ◽  
William A Cilby ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Adjuvant Therapy ◽  
External Beam Radiotherapy ◽  
Disease Free Survival ◽  
External Beam ◽  
Free Survival ◽  
Radiotherapy Alone ◽  
Node Metastases ◽  
Disease Free

ObjectiveThe role of the different types of adjuvant treatments in endometrial cancer with para-aortic node metastases is unclear. The aim of this study was to report oncologic outcomes after adjuvant therapy in patients with stage IIIC2 endometrial cancer.MethodsThis retrospective single-institution study assessed patients with stage IIIC2 endometrial cancer who underwent primary surgery from January 1984 to December 2014. All patients had hysterectomy (±salpingo-oophorectomy) plus lymphadenectomy (para-aortic nodes, ±pelvic nodes). We included all patients with stage III endometrial cancer and documented para-aortic lymph node metastases (International Federation of Obstetrics and Gynecologists stage IIIC2). We excluded patients who did not provide consent, who had synchronous cancer, or who underwent neoadjuvant chemotherapy. Follow-up was restricted to the first 5 years post-operatively. Cox proportional hazards models, with age as the time scale, was used to evaluate associations of risk factors with disease-free survival and overall survival.ResultsAmong 105 patients with documented adjuvant therapy, external beam radiotherapy was administered to 25 patients (24%), chemotherapy to 24 (23%), and a combination (chemotherapy and external beam radiotherapy) to 56 (53%) patients. Most patients receiving chemotherapy and external beam radiotherapy (80%) had chemotherapy first. The majority of relapses had a distant component (31/46, 67%) and only one patient had an isolated para-aortic recurrence. Non-endometrioid subtypes had poorer disease-free survival (HR 2.57; 95% CI 1.38 to 4.78) and poorer overall survival (HR 2.00; 95% CI 1.09 to 3.65) compared with endometrioid. Among patients with endometrioid histology (n=60), chemotherapy and external beam radiotherapy improved disease-free survival (HR 0.22; 95% CI 0.07 to 0.71) and overall survival (HR 0.28; 95% CI 0.09 to 0.89) compared with chemotherapy or external beam radiotherapy alone. Combination therapy did not improve prognosis for patients with non-endometrioid histology (n=45).ConclusionsIn our cohort of patients with stage IIIC2 endometrioid endometrial cancer, those receiving chemotherapy and external beam radiotherapy had improved survival compared with patients receiving chemotherapy or external beam radiotherapy alone. However, the prognosis of patients with non-endometrioid endometrial cancer remained poor, regardless of the adjuvant therapy administered. Distant recurrences were the most common sites of failure.

scholarly journals Programmed death ligand-1 protein expression difference in basal like and non-basal like triple negative breast cancer and its association with disease free survival and overall survival: A systematic review

2021 ◽  
Vol 15 (2) ◽  
Author(s):  
Freda Halim ◽  
Hasrayati Agustina ◽  
Yohana Azhar ◽  
Bethy Hernowo
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Disease Free Survival ◽  
Risk Of Bias ◽  
Secondary Outcome ◽  
Original Research ◽  
Free Survival ◽  
Expression Difference ◽  
Disease Free

The study aims to summarize the literature and explore the strength of evidence for PD-L1 expression difference in basal like TNBC and non-basal like TNBC, and association of PD-L1 expression with disease free survival and overall survival in each group. A systematic search of the original research literature through November 29th, 2020, reported according to PRISMA guideline. Eligible studies investigated must have a primary outcome and at least one secondary outcome. Two reviewers independently searched, selected, and assessed quality of studies and risk of bias. Any discrepancies will be resolved by consensus or by consulting a third and fourth author. A total of 6813 articles were screened from which five articles were selected and assessed for quality of studies and risk of bias. Of 5 articles, no similar findings are found regarding the level of PD-L1 expression and its correlation with recurrence and overall survival. There is not enough substantial evidence to support the difference PD-L1 protein expression level in basal and non-basal like TNBC and its association with recurrence and overall survival. Hence, further studies are needed specifically to focus on this problem.

scholarly journals Stage IB Endometrioid Type Endometrial Cancer: The Role of Lymphadenectomy and Adjuvant Radiation Therapy

2018 ◽  
Vol 24 (3) ◽  
pp. 156
Author(s):  
Osman Turkmen ◽  
Tolga Tasci ◽  
Derman Basaran ◽  
Gunsu Comert Kimyon ◽  
Alper Karalök ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Adjuvant Radiotherapy ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Adjuvant Radiation ◽  
Free Survival ◽  
Stage Ib ◽  
Gynecology And Obstetrics ◽  
Disease Free

<p><strong>Objective:</strong> Both performances of lymphadenectomy and benefit of adding adjuvant radiotherapy are controversial for patients with International Federation of Gynecology and Obstetrics stage IB endometrioid type endometrial cancer. We aimed to identify the role of lymphadenectomy and adjuvant radiation therapy as well as clinicopathological prognostic factors for this group of patients.<br /><strong></strong></p><p><strong>Study Design:</strong> Records of all patients (n=132) with stage IB endometrioid endometrial cancer who were referred to or treated in our institution between Jan 1992 and Dec 2013 were retrospectively reviewed. Cox Proportional Hazard Regression Analysis was used to determine the effects of lymphadenectomy and adjuvant radiation as well as other clinicopathological factors on disease free survival and overall survival.</p><p><strong>Results:</strong> Mean age was 59.9 years (range, 45-82). Lymphadenectomy didn't perform in 36 (27.3%) patients and 23 (17.4%) patients did not have any kind of adjuvant treatment. Mean lymph node count was 18.8 (range, 3-67). Federation of Gynecology and Obstetrics grade, lymphovascular space invasion, lymphadenectomy, receiving adjuvant treatment and type of received adjuvant therapy were not associated with disease free survival and overall survival for the entire cohort. In a subgroup of patients with grade1&amp;2 tumor, 5-year disease free survival rates were 80% and 50% (p=0.4), respectively and overall survival rates were 94.8% and 93.8% (p=0.2), respectively for patients who had or didn't have adjuvant radiotherapy. While performance of lymphadenectomy was not significantly associated with disease free survival in this subgroup (p=0.56), this association was statistically significant for overall survival (97.9% vs. 86.4%, p=0.04) <br /><strong></strong></p><p><strong>Conclusion:</strong> Benefit of adjuvant radiotherapy in regard to prevention of recurrence needs to be confirmed by further studies. Lymphadenectomy had a survival benefit for patients with myometrial invasion greater than a half of myometrial thickness.</p>

scholarly journals Low hENT1 expression indicates poor prognosis in gemcitabine-treated pancreatic cancer patients

2020 ◽  
Author(s):  
Jianchun Xiao ◽  
Fangyu Zhao ◽  
WenHao LUO ◽  
Gang Yang ◽  
Yicheng Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Treated Group ◽  
Expression Level ◽  
Free Survival ◽  
Tumor Tissues ◽  
Disease Free ◽  
Low Expression

Abstract Background Pancreatic cancer (PC) is still a lethal disease and has a poor prognosis, gemcitabine-based chemotherapy is now the standard regimen in the treatment of pancreatic cancer. Gemcitabine resistance is an important obstacle for effective treatment of patients and improvement in patients’ overall survival (OS) and disease free survival (DFS). Methods We collected the surgical pathological tissue of pancreatic cancer patients who received radical surgery in our hospital from September 2004 to December 2014 continuously. 375 pancreatic cancer tissues and paired adjacent non-tumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of 4 TMAs was reexamined by HE staining. We did immunohistochemistry analysis to test hENT1 expression. The hENT1 antibody was used to measure hENT1 expression in TMAs by IHC staining according to standard protocols. Statistical analyses were performed using SPSS 22.0. The clinical end points of patients were calculated using Kaplan-Meier analysis and differences compared by log-rank test. Cox regression (proportional hazards model) was applied to determine the prognostic values of multivariate factors on patients’ overall survival (OS) and disease free survival (DFS). Results The hENT1 protein expression in tumor tissues was much lower than in normal tissues (80.5±8.8 versus 89.5±8.9, p=0.005). A low hENT1 expression level indicated a significant poor outcome of PC patients, including shortened DFS(21.6±2.8 months versus 36.9±4.0 months, p<0.001) and OS(33.6±3.9 versus 39.6±3.9, p=0.004). A high hENT1 expression level was related to longer DFS (35.7±4.0 versus 20.6±2.7; p<0.0001). Similarly, patients with high hENT1 expression in gemcitabine-treated group showed longer overall survival OS compared with low expression group (39.4±4.0 versus 31.5±3.9, p=0.001). In contrast, no significant difference of DFS and OS was found in non-gemcitabine treated group between the expression level of hENT1 and the prognosis of patients (p=0.413 and p=0.152). A low hENT1 expression level in tumor tissues was an independent risk factor for PC recurrence or metastasis(HR 0.53; 95% CI: 0.39-0.72; p<0.001). In addition, a low expression level of hENT1 (HR 0.60; 95%CI: 0.43-0.82; p=0.001) was independent risk factors for overall survival of PC. Low hENT1 expression level predicted worse OS (HR 0.60; 95%CI: 0.43-0.82; p=0.002) and DFS (HR 0.56; 95%CI: 0.41-0.77; p<0.001) . Conclusion hENT1 was low expressed in tumor tissues and this decreased expression level indicated a worse outcome (including shortened OS and DFS) in patients who received gemcitabine treatment postoperatively.

scholarly journals Preoperative Anemia or Low Hemoglobin Predicts Poor Prognosis in Gastric Cancer Patients: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Xuan-zhang Huang ◽  
Yu-chong Yang ◽  
You Chen ◽  
Cong-cong Wu ◽  
Rui-fang Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Preoperative Anemia ◽  
Free Survival ◽  
Effect Model ◽  
Gastric Cancer Patients ◽  
Disease Free

Background. The prognostic value of preoperative anemia in gastric cancer remains unclear. Therefore, the purpose of the present study is to evaluate the prognostic value of preoperative anemia in gastric cancer. Methods. We searched Embase and PubMed databases for relevant studies from inception to March 2018. The prognostic value of preoperative anemia in gastric cancer was determined by calculating the hazard ratio (HR) and the corresponding 95% confidence interval (CI) as effect measures. A random effect model was used in cases in which there was significant heterogeneity; otherwise, a fixed effect model was used. Statistical analyses were performed using Stata software. Results. Seventeen studies involving 13,154 gastric cancer patients were included. The estimated rate of preoperative anemia was 36% (95%CI=27-44%). The overall survival of preoperative anemia was poor (HR=1.33, 95%CI=1.21-1.45). Moreover, disease-free survival was significantly lower in patients with preoperative anemia compared with those without this condition (HR=1.62, 95%CI=1.13-2.32). These findings were corroborated by the results of subgroup analyses. Conclusions. The results indicate that preoperative anemia predicts poor prognosis in gastric cancer, including overall survival and disease-free survival. Therefore, preoperative anemia may be a convenient and cost-effective blood-derived prognostic marker for gastric cancer.

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