Predictive and Prognostic Properties of Human Equilibrative Nucleoside Transporter 1 Expression in Gemcitabine-Treated Pancreatobiliary Cancer: A Meta-Analysis

2019 ◽  
pp. 1-22 ◽  
Author(s):  
Larissa J. Vos ◽  
Dimas Yusuf ◽  
Arthur Lui ◽  
Zainab Abdelaziz ◽  
Sunita Ghosh ◽  
...  

Purpose Gemcitabine, the primary drug for the treatment of pancreatobiliary cancer (PBC), requires human equilibrative nucleoside transporter 1 (hENT1) to enter cells. High tumoral hENT1 expression has been linked with improved survival among patients with PBC treated with gemcitabine; however, this finding has been inconsistent, and studies used different expression assays. Methods Databases were reviewed for studies that examined hENT1 and clinical outcome in PBC. Of 307 publications, 34 studies were found that used immunohistochemistry (IHC) with one of eight anti–hENT1 antibody assays. Five studies were excluded for redundancy, and 29 studies underwent detailed review. Results On average, 51% of tumor samples had high hENT1 expression (range, 7% to 92%). Among studies that examined hENT1 expression and overall survival (OS), 58% (15 of 26 studies) showed an association between high tumoral hENT1 and improved OS for gemcitabine-treated patients. Among 10D7G2 antibody studies, 88% (seven of eight studies) demonstrated this association. Studies with other antibodies—in particular, SP120 (two of nine studies)—were less consistent. The ability to detect an association between improved OS and high hENT1 was antibody dependent (χ2 P = .0237). An association between high tumoral hENT1 expression and improved disease-free/progression-free survival (DFS/PFS) was demonstrated in 71% of studies (15 of 21 studies). Pooled hazard ratio (HR) analyses of all antibody studies demonstrated a link between high hENT1 tumor expression and improved OS (HR, 0.674; 95% CI, 0.509 to 0.893; P = .006) and DFS/PFS (HR, 0.740; 95% CI, 0.517 to 0.1.059; P = .10). This signal was stronger among studies that used the 10D7G2 antibody in comparison to those in which another antibody was used, with HRs of 0.488 (95% CI, 0.396 to 0.602; P < .001) and 0.410 (95% CI, 0.280 to 0.599; P < .001), respectively. Conclusion High tumoral hENT1 expression on IHC with 10D7G2 is a strong and reproducible prognostic marker for improved outcome among gemcitabine-treated patients with PBC.

2018 ◽  
Vol 50 (1) ◽  
pp. 66-78 ◽  
Author(s):  
Qingyan Mao ◽  
Zhen Chen ◽  
Kun Wang ◽  
Renfang Xu ◽  
Hao Lu ◽  
...  

Background/Aims: Several recent studies have demonstrated that Stathmin 1expression may be closely associated with prognosis in patients with various types of cancers. In the present study, we conducted a meta-analysis of all available studies in the English literature to assess the prognostic value of Stathmin 1expression in patients with solid cancers. Methods: The online databases PubMed, Embase, and Web of Science were searched for literature regarding Stathmin 1 and its association with patient outcomes associated with solid cancers. Results: A total of 23 articles including 26 studies that contained 5 335 patients were retrieved and analyzed. Our results indicated that high Stathmin 1 expression yielded a worse overall survival (OS) (hazard ratio [HR] = 2.17, 95% confidence interval [CI]: 1.81–2.60), disease-free survival (DFS) (HR = 2.46, 95% CI: 2.00–3.02), disease-specific survival (DSS) (HR = 1.98, 95% CI: 1.58– 2.47) and progression-free survival (PFS)/recurrence-free survival (RFS) (HR = 2.09, 95% CI: 1.51–2.89). Furthermore, the association of high Stathmin 1 expression with poor survival was significant even for sub-group analyses of different tumor types, ethnicities, methods used to calculate HRs, detected methods, and analysis types. Conclusion: In summary, this meta-analysis determined that high Stathmin 1 expression is associated with poor prognosis in patients with solid cancers and expression of this protein could be a clinically useful prognostic biomarker.


2018 ◽  
Vol 33 (4) ◽  
pp. 372-378 ◽  
Author(s):  
Yuanyuan Hu ◽  
Jie Shen ◽  
RuiKe Liu ◽  
ZhiMei Feng ◽  
ChangNing Zhang ◽  
...  

Background: The pretreatment prognostic nutritional index has been considered a potential prognostic biomarker in patients with non-small cell lung cancer (NSCLC), but this remains controversial. Therefore, we performed a meta-analysis to systematically assess the prognostic value of the prognostic nutritional index in patients with NSCLC. Methods: We systematically searched PubMed, EMBASE, Web of Science, and CNKI. The hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used to evaluate the link between the prognostic nutritional index and the oncological outcomes of patients with NSCLC, including overall survival, disease-free survival/recurrence-free survival, and progression-free survival. Results: Fifteen studies were included in this meta-analysis. Twelve of these studies explored the association between the prognostic nutritional index and the overall survival of patients with NSCLC. Our pooled analysis indicated that a low prognostic nutritional index was significantly related to adverse overall survival (HR 1.61; 95% CI 1.44, 1.81; P < 0.001). Our results also showed that the prognostic nutritional index was a negative predictor for disease-free survival/recurrence-free survival, and progression-free survival in patients with NSCLC. Conclusion: Our meta-analysis demonstrated that there was a close association between the prognostic nutritional index value and prognosis in NSCLC patients and that the prognostic nutritional index may act as a useful prognostic biomarker in NSCLC patients.


2020 ◽  
Author(s):  
Zhao Yang Wang ◽  
Yuanzhu Jiang ◽  
Wen Xiao ◽  
Xianbiao Xue ◽  
Xiangwei Zhang ◽  
...  

Abstract Background: In clinical work, it has been increasingly found that the prognosis is still very different even for esophageal cancer (EC) patients with the same TNM stage. Tumor length has been analysed as a possible independent prognostic factor in many studies, but no unanimous conclusion has been reached. Therefore, this review used a meta-analysis to evaluate the association between tumor length and prognosis in EC patients.Methods: A systematic search for relevant articles was performed in PubMed, Web of Science, and Embase. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effective measures to estimate the correlation between tumor length and prognosis, including overall survival, disease-free survival, progression-free survival, disease-specific survival, and cancer-specific survival. STATA 15.0 software was used to perform the meta-analysis and the data synthesis.Results: Finally, 41 articles with 28,973 patients were included in our study. The comprehensive statistical results showed that long tumors are an independent prognostic parameter associated with poor overall survival (OS) (HR=1.30; 95% CI: 1.21-1.40, p<.001) and disease-free survival (DFS) (HR=1.38; 95% CI: 1.18-1.61, p<.001) in EC patients. Subgroup analyses also suggested a significant correlation between long tumors and poor OS. Sensitivity analysis and publication bias evaluation confirmed the reliability and stability of the results. Similar results were obtained in the analyses of progression-free survival (PFS), disease-specific survival (DSS), and cancer-specific survival (CSS).Conclusion: The results of this meta-analysis showed that long tumors were related to poor OS, DFS, PFS, DSS and CSS in EC patients. Tumor length might be an important predictor of prognosis in EC patients, and it can be used as an independent staging index. Further well-designed and large-scale prospective clinical studies are needed to confirm these findings.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Kai Liao ◽  
Yen-Lin Yu ◽  
Yueh-Chen Lin ◽  
Yu-Jen Hsu ◽  
Yih-Jong Chern ◽  
...  

Abstract Backgrounds The inflammatory biomarker “C-reactive protein to albumin ratio (CAR)” has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. Methods We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. Results A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808−2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321–2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. Conclusions High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.


2013 ◽  
Vol 23 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Dong Zhao ◽  
Fengmei Zhang ◽  
Wei Zhang ◽  
Jing He ◽  
Yulan Zhao ◽  
...  

ObjectiveThe aim of this study was to summarize the global predicting role of hormone receptors for survival in ovarian cancer.MethodsEligible studies were identified and assessed for quality through multiple search strategies. Data were collected from studies comparing overall or progression-free/disease-free/relapse-free survival in patients with elevated levels of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) with those in patients with lower levels. Studies were pooled, and combined hazards ratios (HRs) of ER, PR, and HER2 for survival were calculated, respectively.ResultsA total of 35 studies were included for meta-analysis (23 for ER, 19 for PR, and 8 for HER2). For overall survival, the pooled HR of PR reached 0.88 [95% confidence interval (CI), 0.82-0.95], which means that elevated PR level could significantly indicate better survival. In contrast, elevated levels of HER2 could predict worse outcome with an HR of 1.41 (95% CI, 1.05–1.89). Increased level of ER was not significantly prognostic (HR, 0.94; 95% CI, 0.87–1.01). For progression-free survival/disease-free survival/recurrence-free survival, elevated PR level also had predictive value for better outcome with a pooled HR of PR of 0.80 (95% CI, 0.67–0.95). Oppositely, elevated HER2 level could predict poorer outcome with an HR of 1.55 (95% CI, 1.11–2.16). Estrogen receptor failed to predict outcome with an HR of 0.90 (95% CI, 0.78–1.03).ConclusionsIn patients with ovarian cancer, elevated level of PR predicted favorable survival, and elevated level of HER2 was associated with worse survival.


2018 ◽  
Vol 33 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Younghoon Kim ◽  
Xianyu Wen ◽  
Nam Yun Cho ◽  
Gyeong Hoon Kang

Background: The prognostic value of immune cells expressing programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) in cancer are controversial, and the potential differential impact of using tissue microarrays and whole tissue sections to assess the positivity of immune cells has not been addressed. Methods: The current study included 30 eligible studies with 7251 patients that evaluated the relationship between tumor-infiltrating lymphocytes expressing PD-1/PD-L1 and overall survival and disease-free survival, or progression-free survival. Subgroup analysis was based on the tissue type of cancer and the type of tissue sampling (tissue microarray or whole tissue section). Results: In the meta-analysis, PD-1-positive and PD-L1-positive tumor-infiltrating lymphocytes had a positive effect on disease-free survival or progression-free survival (hazard ratio [HR] 0.732; 95% confidence interval [CI] 0.565, 0.947; and HR 0.727; 95% CI 0.584, 0.905, respectively). PD-L1-positive tumor-infiltrating lymphocytes had a positive impact on overall survival in studies using tissue microarray (HR 0.586; 95% CI 0.476, 0.721), but had a poor impact when only whole tissue sections were considered (HR 1.558; 95% CI 1.232, 1.969). Lung cancer was associated with good overall survival and disease-free survival (HR 0.639; 95% CI 0.491, 0.831; and HR 0.693; 95% CI 0.538, 0.891, respectively) for PD-1-positive tumor-infiltrating lymphocytes, and colorectal cancer showed favorable disease-free survival (HR 0.471; 95% CI 0.308, 0.722) for PD-L1-positive tumor-infiltrating lymphocytes. Conclusion: Immune cells expressing PD-1 and PD-L1 within tumors are associated with the prognosis. However, the correlation may vary among different tumor types and by the type of tissue sampling used for the assessment.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elahe Seyed Hosseini ◽  
Ali Nikkhah ◽  
Amir Sotudeh ◽  
Marziyeh Alizadeh Zarei ◽  
Fatemeh Izadpanah ◽  
...  

Abstract Purpose An increasing number of studies have reported a significant association between long non-coding RNAs (lncRNAs) dysregulation and pancreatic cancers. In the present study, we aimed to gather articles to evaluate the prognostic value of long non coding RNA in pancreatic cancer. Experimental design We systematically searched all eligible articles from databases of PubMed, Web of Science, and Scopus to meta-analysis of published articles and screen association of multiple lncRNAs expression with clinicopathology and/or survival of pancreatic cancer. The pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were used to analysis of overall survival, disease-free survival and progression-free survival were measured with a fixed or random effects model. Results A total of 39 articles were included in the present meta-analysis. Our results showed that dysregulation of lncRNAs were linked to overall survival (39 studies, 4736 patients HR = 0.41, 95% CI 0.25 ± 0.58, random-effects in pancreatic cancer. Moreover, altered lncRNAs were also contributed to progression-free survival (8 studies, 1180 patients HR: 1.88, 95% CI (1.35–2.62) and disease-free survival (2 studies, 285 patients, HR: 6.07, 95% CI 1.28–28.78). In addition, our findings revealed the association between dysregulated RNAs and clinicopathological features in this type of cancer. Conclusions In conclusion, dysregulated lncRNAs could be served as promising biomarkers for diagnosis and prognosis of pancreatic cancer.


2021 ◽  
Vol 10 (20) ◽  
pp. 4652
Author(s):  
Jung Won Chun ◽  
Boyoung Lee ◽  
Weon Seo Park ◽  
Nayoung Han ◽  
Eun Kyung Hong ◽  
...  

The combination of gemcitabine plus cisplatin (GP) is regarded as a first-line treatment for patients with unresectable or recurrent biliary tract cancer (BTC). Several proteins including human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (DCK), cytidine deaminase (CDA), and ribonucleotide reductase subunit 1 (RRM1) are known to be involved in gemcitabine uptake and metabolism. This study was aimed to identify the predictive and prognostic values of these biomarkers in patients who treated with GP for advanced BTC. Tumor samples were obtained from 34 patients with unresectable or recurrent BTC who were treated with GP between August 2015 and February 2018. Intratumoral expression of hENT1, DCK, CDA and RRM1 was determined by immunohistochemistry and analyzed for association with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Median OS was significantly longer in the RRM1-negative group than in the RRM1-positive (9.9 months vs. 5.9 months, p = 0.037). Multivariate adjustment analyses also demonstrated RRM1 expression as an independent prognostic factor for OS in patients treated with GP chemotherapy. Increased intratumoral expression of RRM1 on immunohistochemical staining may be a biomarker predicting poor survival in patients with GP chemotherapy for advanced BTC. Large-scale well-predefined prospective research is needed to validate the utility of biomarkers in clinical practice.


2021 ◽  
Vol 36 (2) ◽  
pp. 172460082110326
Author(s):  
Wenfeng Liu ◽  
Keshu Hu ◽  
Feng Zhang ◽  
Shenxin Lu ◽  
Rongxin Chen ◽  
...  

Background Recently, microRNA-221 has been found to be abnormally expressed in hepatocellular carcinoma; however, its clinical value has not been summarised. This meta-analysis aimed to assess the prognostic significance of miR-221 in hepatocellular carcinoma. Material and Methods PubMed, Science Direct, Web of Science, Scopus, Ovid MEDLINE, EMbase, Google Scholar, the Cochrane Library, CNKI, CBM, VIP and Wanfang databases were searched for eligible articles. The endpoints included overall survival, progression-free survival, recurrence-free survival, metastasis-free survival, disease-free survival. Hazard ratios with 95% confidence intervals were used to explore the relationship between miR-221 expression and clinical survival results of liver cancer patients. Subgroup analysis and sensitivity analysis were performed. Begg’s test and Egger’s test were conducted to evaluate publication bias. Results A total of nine studies including 607 patients were recruited for this meta-analysis. The pooled hazard ratios displayed that high miR-221 expression was remarkably associated with poorer overall survival (hazard ratio = 1.91, 95% confidence interval: 1.53–2.38, p < 0.01) and unfavourable progression-free survival/recurrence-free survival/metastasis-free survival/disease-free survival (hazard ratio = 2.02, 95% confidence interval: 1.58–2.57, p < 0.01). The results of Begg’s test and Egger’s test did not exhibit obvious publication bias. Conclusions High expression of miR-221 can predict poor outcome of hepatocellular carcinoma. miR-221 can be used as a promising prognostic biomarker of hepatocellular carcinoma.


2020 ◽  
Vol 36 (1) ◽  
pp. 117-130
Author(s):  
Shuxia Wang ◽  
Bo Yuan ◽  
Yun Wang ◽  
Mingyang Li ◽  
Xibo Liu ◽  
...  

Abstract Purpose To systematically evaluate the correlation between PD-L1 expression and clinicopathological features and prognosis of colorectal cancer (CRC). Methods Seven databases (PubMed, Cochrane Library, EMBASE, Web of Science, CBM, Wanfang, and CNKI) were searched through May 2020. Risk of bias and quality of evidence were assessed by using the Newcastle–Ottawa scale (NOS), and meta-analysis was carried out by using the Review Manager 5.3 software on the studies with the quality evaluation scores ≥ 6. Meta-regression analysis was used to determine the independent role of PD-L1 expression on CRC prognosis after adjusting clinicopathological features and treatment methods. Results A total of 8823 CRC patients in 32 eligible studies. PD-L1 expression was correlated with lymphatic metastasis (yes/no; OR = 1.24, 95% CI (1.11, 1.38)), diameter of tumor (≥ 5 cm/< 5 cm; OR = 1.34, 95% CI (1.06, 1.70)), differentiation (high–middle/low; OR = 0.68, 95% CI (0.53, 0.87)), and vascular invasion (yes/no; OR = 0.80, 95% CI (0.69, 0.92)). PD-L1 expression shortened the overall survival (hazard ratio (HR) = 1.93, 95% CI (1.66, 2.25)), disease-free survival (HR = 1.76, 95% CI (1.50, 2.07)), and progression-free survival (HR = 1.93, 95% CI (1.55, 2.41)). Meta-regression showed that PD-L1 expression played a significant role on poor CRC OS (HR = 1.95, 95% CI (1.92, 3.98)) and disease-free survival (HR = 2.14, 95% CI (0.73, 4.52)). Conclusion PD-L1 expression independently predicted a poor prognosis of CRC.


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