MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis

The role of several metabolic changes, such as hypoxia and acidosis, in the tumour environment has caught the attention of researchers in cancer progression and invasion. Lactate transport is one of the acidosis-enhancing processes that are mediated via monocarboxylate transporters (MCTs). We conducted a systematic review and meta-analysis to investigate the expression of two cancer-relevant MCTs (MCT1 and MCT4) and their potential prognostic significance in patients with metastasis of different types of cancer. Studies were included if they reported the number of metastatic tissue samples expressing either low or high levels of MCT1 and/or MCT4 or those revealing the hazard ratios (HRs) of the overall survival (OS) or disease-free survival (DFS) as prognostic indicators. During the period between 2010 and 2018, a total of 20 articles including 3831 patients (56.3% males) were identified. There was a significant association between MCT4 expression (high versus low) and lymph node metastasis [odds ratio (OR)=1.87, 95% confidence interval (CI)=1.10-3.17, P=0.02] and distant metastasis (OR=2.18, 95%CI=1.65-2.86, P<0.001) and the correlation remained significant for colorectal and hepatic cancer in subgroup analysis. For survival analysis, patients with shorter OS periods exhibited a higher MCT4 expression [hazard ratio (HR)=1.78, 95%CI=1.49-2.13, P<0.001], while DFS was shorter in patients with high MCT1 (HR=1.48, 95%CI=1.04-2.10, P=0.03) and MCT4 expression (HR=1.70, 95%CI=1.19-2.42, P=0.003) when compared to their counterparts with low expression levels. Future research studies should consider the pharmacologic inhibition of MCT4 to effectively inhibit cancer progression to metastasis.

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The Clinicopathologic and Prognostic Significance of c-Myc Expression in Hepatocellular Carcinoma: A Meta-Analysis

Frontiers in Bioinformatics ◽

10.3389/fbinf.2021.706835 ◽

2021 ◽

Vol 1 ◽

Author(s):

Zhao Min ◽

Zhang Xunlei ◽

Chen Haizhen ◽

Zhao Wenjing ◽

Yu Haiyan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Publication Bias ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Cochrane Library ◽

Poor Overall Survival ◽

Hazard Ratios ◽

Incidence And Mortality

Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing worldwide. Therefore, there is an urgent need to elucidate the molecular drivers of HCC for potential early diagnosis and individualized treatment. Whether c-Myc expression plays a role in the clinicopathology and prognosis of patients with HCC remains controversial. This meta-analysis aimed to survey the prognostic role of c-Myc in HCC.Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, and Google Scholar databases for studies published through March 2020 that examined the association between c-Myc expression and clinicopathology or prognosis in HCC patients. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to investigate the prognostic significance of c-Myc expression. Odds ratios were calculated to evaluate the association between c-Myc expression and clinicopathologic features. We also tested for publication bias.Results: Our meta-analysis included nine studies with 981 patients with HCC published between 1999 and 2016. A meta-analysis of these studies demonstrated that high c-Myc expression indicated a poor overall survival (OS) (HR = 2.260, 95% CI: 1.660–3.080, and p < 0.001) and disease-free survival (DFS) (HR = 1.770, 95% CI: 1.430–2.450, and p < 0.001) in patients with HCC. However, high c-Myc expression was not associated with HBsAg, pathological type, TNM stage, or cirrhosis. We did not find any significant publication bias among the included studies, indicating that our estimates were robust and reliable.Conclusion: c-Myc overexpression could predict poor OS and DFS in HCC patients. c-Myc could be a useful prognostic biomarker and therapeutic target for HCC.

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Prognostic significance of NEK2 in human solid tumors: a systematic review and meta-analysis

Bioscience Reports ◽

10.1042/bsr20180618 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 1

Author(s):

Xichen Wang ◽

Kang Chen ◽

Haipeng Liu ◽

Zeping Huang ◽

Xiao Chen ◽

...

Keyword(s):

Solid Tumors ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Pooled Analysis ◽

Prognostic Role ◽

Free Survival ◽

Hazard Ratios ◽

Human Solid Tumors

AbstractA consensus about the prognostic role of NIMA-related kinase 2 (NEK2) expression in various solid tumors has not been made yet. Thus, this meta-analysis aimed to systematically assess the prognostic role of NEK2 expression in patients with solid tumors. The eligible studies were identified through searching PubMed, Web of Science, and EMBASE. The hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used to evaluate the link between NEK2 overexpression and overall survival (OS) and disease-free survival/recurrence-free survival (DFS/RFS) of patients with solid tumors. A total of 17 studies with 4897 patients were included in this meta-analysis. Among these studies, all of them explored the association between NEK2 expression and OS of patients with solid tumors. Our pooled analysis indicated that NEK2 overexpression was significantly related to adverse OS (HR = 1.66; 95% CI: 1.38–2.00; P = 0.001). Additionally, there were six studies with 854 patients that investigated the association between NEK2 expression and DFS/RFS. Our pooled result indicated that there was a substantial relationship between NEK2 overexpression and poorer DFS/RFS (HR = 2.00; 95% CI: 1.61–2.48; P = 0.003). In conclusion, our meta-analysis indicated that NEK2 may be a useful predictor of prognosis and an effective therapeutic target in solid tumors. Nevertheless, more high-quality studies are warranted to further support our conclusions because of several limitations in our meta-analysis.

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732 Delay to Elective Colorectal Cancer Surgery and its Potential Implications During the Covid-19 Pandemic: A Systematic Review and Metanalysis

British Journal of Surgery ◽

10.1093/bjs/znab259.817 ◽

2021 ◽

Vol 108 (Supplement_6) ◽

Author(s):

T Whittaker ◽

M Abdelrazek ◽

A Fitzpatrick ◽

J Froud ◽

J Kelly ◽

...

Keyword(s):

Colorectal Cancer ◽

Systematic Review ◽

Elective Surgery ◽

Meta Analysis ◽

Disease Free Survival ◽

Colorectal Cancer Surgery ◽

Elective Resection ◽

Hazard Ratios ◽

Patient Groups ◽

Number Needed To Harm

Abstract Aim The ongoing Covid-19 pandemic has interrupted the surgical treatment of colorectal cancer (CRC). This systematic review will assess literature concerning the risk of delay of elective surgery for CRC patients, focusing on overall survival (OS) and disease-free survival (DFS). Method A systematic review was performed as per PRISMA guidelines (PROSPERO ID: CRD42020189158). Medline, EMBASE and Scopus were searched. Delay to elective surgery was defined as the period between CRC diagnosis and the day of surgery. Metanalyses of the outcome’s OS and DFS were conducted. Forest plots, funnel plots, and tests of heterogeneity were produced. An estimated Number Needed to Harm (NNH) was calculated for statistically significant pooled Hazard Ratios (HRs). Results Of 3753 articles identified, seven met the inclusion criteria. Encompassing 314560 patients, three of the seven studies showed that a delay to elective resection is associated with poorer OS or DFS. OS was assessed at a one-month delay, the HR for six datasets was 1.13 (95%CI 1.02-1.26, p = 0.020) and at three months the pooled HR for three datasets was 1.57 (95%CI 1.16-2.12, p = 0.004). Estimated NNHs for a delay at one month and three months were 35 and 10 respectively. Delay was non-significantly negatively associated with DFS on meta-analysis. Conclusions This review recommends that elective surgery for CRC patients is not postponed, as evidence suggests delays from diagnosis are associated with poorer outcomes. Focused research is essential so that patient groups can be prioritized based on risk factors for future pandemics.

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Preoperative Platelet to Lymphocyte Ratio as a Prognostic Factor for Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

Digestive Surgery ◽

10.1159/000508444 ◽

2020 ◽

Vol 37 (6) ◽

pp. 447-455

Author(s):

Romualdas Riauka ◽

Povilas Ignatavicius ◽

Giedrius Barauskas

Keyword(s):

Systematic Review ◽

Pancreatic Cancer ◽

Prognostic Factor ◽

Meta Analysis ◽

Disease Free Survival ◽

Platelet To Lymphocyte Ratio ◽

Resectable Pancreatic Cancer ◽

Lymphocyte Ratio ◽

Asian Patients ◽

Hazard Ratios

Introduction: Various inflammatory markers have been investigated for a prognostic role in patients with resectable pancreatic cancer. However, the value of preoperative platelet to lymphocyte ratio (PLR) remains controversial. We performed a systematic review and meta-analysis of PLR as a preoperative prognostic factor for resectable pancreatic cancer. Material and Methods: Systematic literature search was conducted for studies assessing PLR influence as a preoperative prognostic factor in resectable pancreatic cancer patients. Random-effects model was applied for pooling hazard ratios and 95% confidence intervals related to overall survival (OS) and disease-free survival (DFS). Results: Fourteen articles with 2,743 patients were included in the study. According to the analysis, high PLR had no correlation with decreased OS. Due to high heterogeneity among studies, subgroup analysis was performed. Better OS was associated with low PLR in Asian patients, patients with mixed type of operation performed, and patients with preoperative PLR ≤150. Low PLR was associated with significantly better DFS. Conclusions: PLR is a predictive factor of better DFS in patients with resectable pancreatic cancer. However, available evidence does not support PLR as a reliable prognostic factor for OS.

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Prognostic Significance of microRNA-221/222 Expression in Cancers: Evidence from 1,204 Subjects

The International Journal of Biological Markers ◽

10.5301/jbm.5000058 ◽

2014 ◽

Vol 29 (2) ◽

pp. 129-141 ◽

Cited By ~ 4

Author(s):

Jin Wang ◽

Sha Liu ◽

Guo Ping Sun ◽

Fang Wang ◽

Yan Feng Zou ◽

...

Keyword(s):

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Published Data ◽

Cancer Type ◽

Free Survival ◽

Patients With Cancer ◽

Elevated Expression ◽

Strength Of Association

Background The prognostic significance of the expression of the miR-221/222 family in cancer remains controversial. We here performed a meta-analysis of published data investigating the effects of miR-221/222 expression on both overall survival (OS) and disease-free survival (DFS) among patients with cancer. Methods A systematic search of the PubMed, Embase, Cochrane, and CNKI databases was performed with the last search being updated on March 15, 2013. The hazard ratio (HR) and its 95% confidence interval (95% CI) were used to assess the strength of association. Results A total of 17 studies involving 1,204 subjects were included in this meta-analysis. When assessing the prognostic significance of miR-221 expression, the pooled HR was 1.91 (95% CI: 1.28-2.85, p=0.002) for OS and 1.36 (95% CI: 0.88-2.09, p=0.163) for DFS. When assessing the prognostic significance of miR-222 expression, the pooled HR was 2.15 (95% CI: 1.51-3.06, p<0.0001) for OS and 1.37 (95% CI: 0.45-4.13, p=0.581) for DFS. We also found that an elevated miR-221 expression was significantly associated with poor OS when stratifying by ethnicity, cancer type, statistical methodology, sample, and quality assessment. There was no evidence of publication bias. Conclusion The meta-analysis demonstrates that the elevated expression of miR-221 and miR-222 is associated with poor OS in patients with cancer. The miR-221/222 cluster might be used as a potential therapeutic strategy in clinical practice. More work is required to fully elucidate the role of the miR-221/222 family in human tumors.

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Tumor-Infiltrating Podoplanin+ Fibroblasts Predict Worse Outcome in Solid Tumors

Cellular Physiology and Biochemistry ◽

10.1159/000495484 ◽

2018 ◽

Vol 51 (3) ◽

pp. 1041-1050 ◽

Cited By ~ 6

Author(s):

Guoming Hu ◽

Shimin Wang ◽

Feng Xu ◽

Qiannan Ding ◽

Wei Chen ◽

...

Keyword(s):

Pancreatic Cancer ◽

Solid Tumors ◽

Solid Tumor ◽

Meta Analysis ◽

Disease Free Survival ◽

Clinicopathological Features ◽

Immunohistochemical Method ◽

Hazard Ratios ◽

Human Solid Tumors

Background/Aims: Tumor-infiltrating fibroblasts are a heterogeneous population, and different subpopulations play differential roles in tumor microenvironment. However, the prognostic role of podoplanin+ fibroblasts in human solid tumors still remains controversial. Therefore, we performed the meta-analysis to better understand the role of this subpopulation in prognosis prediction for patients with solid tumor. Methods: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral podoplanin+ fibroblast density detected by immunohistochemical method and overall survival (OS) and/or disease-free survival (DFS) in patients with solid tumor, then computed extracted data into hazard ratios for OS, DFS and clinicopathological features with STATA 12.0. Results: A total of 4883 patients from 29 published studies were incorporated into this meta-analysis. We found that podoplanin+ fibroblast infiltration significantly decreased OS and DFS in all types of solid tumors. In stratified analyses, podoplanin+ fibroblast infiltration was significantly associated with worse OS in cholangiocarcinoma, breast, lung and pancreatic cancer. And these cells were inversely associated with DFS in breast, lung and pancreatic cancer. In addition, high density of these cells significantly correlated with unfavorable clinicopathological features such as lymph node metastasis, TNM stage, lymphatic and vascular invasion of solid tumor. Conclusion: Podoplanin+ fibroblast infiltration leads to worse clinical outcome in solid tumors, implicating that it is a valuable prognostic biomarker and targeting it may have a potential for effective treatment.

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Prognostic Role of Platelet-to-Lymphocyte Ratio in Hepatocellular Carcinoma with Different BCLC Stages: A Systematic Review and Meta-Analysis

Gastroenterology Research and Practice ◽

10.1155/2018/5670949 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Wan-fu Lin ◽

Mao-feng Zhong ◽

Yu-ren Zhang ◽

Huan Wang ◽

He-tong Zhao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Meta Analysis ◽

Disease Free Survival ◽

Clinical Event ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Statistical Heterogeneity ◽

Event Occurrence

The role of platelet-to-lymphocyte ratio (PLR) in the prognosis of hepatocellular carcinoma (HCC) patients with different Barcelona Clinic Liver Cancer (BCLC) stages remains controversial. This systematic review and meta-analysis aimed to determine the efficacy of PLR on HCC prognosis. Five electronic databases were searched for clinical trials focusing on the role of PLR in the prognosis of HCC. A total of 297 potential studies were initially identified, and 9 studies comprising 2449 patients were finally enrolled to evaluate the association between the pretreatment PLR and clinical outcomes of overall survival (OS), disease-free survival (DFS), and event occurrence in patients with HCC in different BCLC stages. An elevated pretreatment PLR indicated unfavorable worse OS (HR = 1.73; 95% CI: (1.46, 2.04); P<0.00001) and DFS (HR = 1.30; 95% CI: (1.06, 1.60); P=0.01). Subgroup analysis indicated that high PLR indicated poor OS among BCLC-B/C patients without heterogeneity, while PLR in BCLC-A patients indicated high statistical heterogeneity with I2 value of 78%. As for the correlation between PLR and event occurrence, high PLR was related to poor clinical event occurrence only among BCLC-C patients, though obvious heterogeneity was observed in all different BCLC stages. In conclusion, PLR may be a significant biomarker in the prognosis of HCC in different BCLC stages.

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A systematic review of the relationship between behavioral and psychological symptoms (BPSD) and caregiver well-being

International Psychogeriatrics ◽

10.1017/s1041610216000922 ◽

2016 ◽

Vol 28 (11) ◽

pp. 1761-1774 ◽

Cited By ~ 78

Author(s):

Alexandra Feast ◽

Esme Moniz-Cook ◽

Charlotte Stoner ◽

Georgina Charlesworth ◽

Martin Orrell

Keyword(s):

Systematic Review ◽

Motor Behavior ◽

Psychological Symptoms ◽

Meta Analysis ◽

Well Being ◽

Future Research ◽

The Individual ◽

The Impact ◽

Behavioral And Psychological Symptoms

ABSTRACTBackground:Behavioral and psychological symptoms in dementia (BPSD) are important predictors of institutionalization as well as caregiver burden and depression. Previous reviews have tended to group BPSD as one category with little focus on the role of the individual symptoms. This review investigates the role of the individual symptoms of BPSD in relation to the impact on different measures of family caregiver well-being.Methods:Systematic review and meta-analysis of papers published in English between 1980 and December 2015 reporting which BPSD affect caregiver well-being. Paper quality was appraised using the Downs and Black Checklist (1998).Results:Forty medium and high quality quantitative papers met the inclusion criteria, 16 were suitable to be included in a meta-analysis of mean distress scores. Depressive behaviors were the most distressing for caregivers followed by agitation/aggression and apathy. Euphoria was the least distressing. Correlation coefficients between mean total behavior scores and mean distress scores were pooled for four studies. Irritability, aberrant motor behavior and delusions were the most strongly correlated to distress, disinhibition was the least correlated.Conclusions:The evidence is not conclusive as to whether some BPSD impact caregiver well-being more than others. Studies which validly examined BPSD individually were limited, and the included studies used numerous measures of BPSD and numerous measures of caregiver well-being. Future research may benefit from a consistent measure of BPSD, examining BPSD individually, and by examining the causal mechanisms by which BPSD impact well-being by including caregiver variables so that interventions can be designed to target BPSD more effectively.

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Prognostic and Clinicopathological Significance of PD-L1 in Patients with Cholangiocarcinoma: A Meta-Analysis

Disease Markers ◽

10.1155/2020/1817931 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Qinfen Xie ◽

Lidong Wang ◽

Shusen Zheng

Keyword(s):

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Cochrane Library ◽

Free Survival ◽

Hazard Ratios ◽

Programmed Death ◽

Poor Differentiation ◽

Clinicopathological Significance ◽

Pn Stage

Background. In recent years, there is growing literature on the prognostic significance of programmed death-ligand 1 (PD-L1) in cholangiocarcinoma (CCA); however, data have been conflicting. Therefore, the objective of this study was to assess the correlation between PD-L1 and prognosis in CCA through meta-analysis. Methods. Published studies were retrieved from the Web of Science, PubMed, Embase, and Cochrane Library up to April 17, 2020. The relationships between PD-L1 expression and survival outcomes were assessed using hazard ratios (HRs) and 95% confidence intervals (CIs). Results. Eighteen studies consisting of 2012 patients were included. Overexpression of PD-L1 was significantly associated with worse overall survival (OS) (HR=1.58, 95%CI=1.30−1.92, p<0.001) but not with poor disease-free survival (DFS) (HR=1.03, 95%CI=0.68−1.55, p=0.895) in CCA. Moreover, PD-L1 was associated with low differentiation (OR=1.43, 95%CI=1.09−1.87, p=0.010) and higher pN stage (OR=1.45, 95%CI=1.10−1.92, p=0.009) but not with sex, TNM stage, vascular invasion, perineural invasion, age, or tumor size. Conclusion. High PD-L1 expression was associated with worse OS, poor differentiation, and higher pN stage in patients with CCA. PD-L1 could be a potential prognostic marker in CCA.

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Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis

Cancer Cell International ◽

10.1186/s12935-020-1094-5 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Jiawen Zhao ◽

Weijia Huang ◽

Yongxian Wu ◽

Yihuan Luo ◽

Bo Wu ◽

...

Keyword(s):

Systematic Review ◽

Solid Tumors ◽

Clinical Outcomes ◽

Lymphocyte Count ◽

Meta Analysis ◽

Progression Free Survival ◽

Prognostic Impact ◽

Cancer Type ◽

Hazard Ratios

Abstract Background To evaluate the prognostic value of pretreatment lymphocyte counts with respect to clinical outcomes in patients with solid tumors. Methods Systematic literature search of electronic databases (Pubmed, Embase and Web of Science) up to May 1, 2018 was carried out by two independent reviewers. We included Eligible studies assessed the prognostic impact of pretreatment lymphocytes and had reported hazard ratios (HR) with 95% confidence intervals (CIs) for endpoints including overall survival (OS) and progression-free survival (PFS). Only English publications were included. Results A total of 42 studies comprising 13,272 patients were included in this systematic review and meta-analysis. Low pretreatment lymphocyte count was associated with poor OS (HR = 1.27, 95% CI 1.16–1.39, P < 0.001, I2 = 58.5%) and PFS (HR = 1.27, 95% CI 1.15–1.40, P < 0.001, I2 = 25.7%). Subgroup analysis disaggregated by cancer type indicated that low pretreatment lymphocytes were most closely associated with poor OS in colorectal cancer followed by breast cancer and renal cancer. Conclusions Low pretreatment lymphocyte count may represent an unfavorable prognostic factor for clinical outcomes in patients with solid tumors.

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