The Prognostic and Clinical Value of CD44 in Colorectal Cancer: A Meta-Analysis.
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ABSTRACT:
SUBMITTER: Wang Z
PROVIDER: S-EPMC6503057 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Project description:ObjectiveLeucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has recently been reported to be a marker of cancer stem cells (CSCs) in colorectal cancer (CRC), and the prognostic value of LGR5 in CRC has been evaluated in several studies. However, the conclusions remain controversial. In this study, we aimed to evaluate the association between the expression of LGR5 and the outcome of CRC patients by performing a meta-analysis.MethodsWe systematically searched for relevant studies published up to February 2014 using the PubMed, Web of Science, EMBASE and Wangfang databases. Only articles in which LGR5 expression was detected by immunohistochemistry were included. A meta-analysis was performed using STATA 12.0, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between LGR5 expression and the prognosis of CRC patients.ResultsA total of 7 studies comprising 1833 CRC patients met the inclusion criteria, including 6 studies comprising 1781 patients for overall survival (OS) and 3 studies comprising 528 patients for disease-free survival (DFS). Our results showed that high LGR5 expression was significantly associated with poor prognosis in terms of OS (HR: 1.87, 95% CI: 1.23-2.84; P?=?0.003) and DFS (HR: 2.44, 95% CI: 1.49-3.98; P<0.001). Further subgroup analysis revealed that many factors, including the study region, number of patients, follow-up duration and cutoff value, affected the significance of the association between LGR5 expression and a worse prognosis in patients with CRC. In addition, there was no evidence of publication bias, as suggested by Begg's and Egger's tests.ConclusionsThe present meta-analysis indicated that high LGR5 expression was associated with poor prognosis in patients with CRC and that LGR5 is an efficient prognostic factor in CRC.
| S-EPMC4156381 | biostudies-literature
Project description:Objective: Cancer stem cell marker CD44 and its variant isoforms (CD44v) may be correlated with tumor growth, metastasis, and chemo-radiotherapy resistance. However, the prognostic power of CD44 and CD44v in advanced cancer remains controversial. Therefore, the purpose of our study was to generalize the prognostic significance of these cancer stem cell markers in advanced cancer patients. Methods: Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from multivariable analysis to assess the associations among CD44, CD44v6, and CD44v9 positivity and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), and recurrence-free survival (RFS). Trial sequential analysis (TSA) was also conducted. Results: We included 15 articles that reported on 1,201 patients with advanced cancer (CD44: nine studies with 796 cases, CD44v6: three studies with 143 cases, and CD44v9: three studies with 262 cases). CD44 expression was slightly linked to worse OS (HR = 2.03, P = 0.027), but there was no correlation between CD44 expression and DFS, RFS, or PFS. Stratified analysis showed that CD44 expression was not correlated with OS at ≥5 years or OS in patients receiving adjuvant therapy. CD44v6 expression was not associated with OS. CD44v9 expression was closely associated with poor 5-years CSS in patients treated with chemo/radiotherapy (HR = 3.62, P < 0.001). However, TSA suggested that additional trials were needed to confirm these conclusions. Conclusions: CD44 or CD44v9 might be novel therapeutic targets for improving the treatment of advanced cancer patients. Additional prospective clinical trials are strongly needed across different cancer types.
| S-EPMC6372530 | biostudies-literature
Project description:BackgroundColorectal cancer (CRC) is the third most prevalent cancer type and the third leading cause of cancer-related deaths worldwide, it is urgently needed to discover a new marker for the progress of CRC. Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in CRC, and may be feasible as effective biomarkers and prognostic factors. The aim of this study was to identify the prognostic value of various lncRNAs in CRC.MethodsPubmed, Web of Science, Embase and Cochrane Library were searched for potentially related studies. A total of 34 eligible studies including 30 on overall survival (OS), 7 on disease-free survival (DFS), 1 on relapse-free survival (RFS), 2 on disease-specific survival (DSS) and 29 on clinicopathological features were qualified from the databases.ResultsThe results showed that the expression levels of lncRNAs were significantly associated with poor OS (hazard ratio (HR) = 2.08, 95% confidence interval (CI) = 1.68-2.57, P<0.001, I2 = 70%), DFS (HR = 1.79, 95% CI = 1.54-2.08, P<0.001, I2 = 6%) and DSS (HR = 0.11, 95% CI = 0.02-0.54, P = 0.007, I2 = 14%). Subgroup analysis further showed that lncRNA transcription level was significantly associated with tumor differentiation (odds ratio (OR) = 0.51, 95% CI = 0.34-0.77, P = 0.001), lymph node metastasis (OR = 1.63, 95% CI = 1.23-2.17, P = 0.0007), distant metastasis (OR = 2.06, 95% CI = 1.29-3.30, P = 0.002), TNM stage (OR = 0.44, 95% CI = 0.32-0.62, P<0.001), tumor invasion depth (OR = 0.48, 95% CI = 0.39-0.60, P<0.001).ConclusionsThe meta-analysis demonstrated that abnormal lncRNA transcription level may serve as a promising indicator for prognostic of patients with CRC.
| S-EPMC5489187 | biostudies-literature
Project description:BackgroundAccumulating evidence supports the overexpression of mucin 1 (MUC1) in colorectal cancer (CRC), but the value of elevated MUC1 expression remains controversial. Here, we evaluated the prognostic and clinicopathological value of MUC1 expression in CRC.Materials and methodsThe Web of Science, PubMed, Embase, Cochrane Library, and Wanfang databases, as well as the China Biology Medicine disc (CBMdisc) and China National Knowledge Infrastructure (CNKI) were searched for studies on MUC1 expression and prognosis of CRC through July 20, 2018. The pooled relative risks (RRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated to evaluate the prognostic and clinicopathological value of MUC1 expression in CRC. The Revman version 5.3 package and STATA, version 12 were employed for pooled analysis and analysis of publication bias.ResultsThis meta-analysis included 16 published studies. The combined analysis showed that CRC patients with high MUC1 expression had a worse clinical outcome in overall survival (OS) (HR = 1.51, 95% CI = 1.30-1.75, P <.00001). In addition, high MUC1 expression was associated with higher TNM stage (RR = 1.44, 95% CI = 1.17-1.77, P = .0007), greater depth of invasion (RR = 1.30, 95% CI = 1.10-1.53, P = .002), and lymph node metastasis (RR = 1.47, 95% CI = 1.20-1.80, P = .0002) of CRC. However, the elevated MUC1 expression was not related to disease-free survival/recurrence-free survival (DFS/RFS) (HR = 1.51, 95% CI = 0.78-2.89, P = .22), histological grade (RR = 1.15, 95% CI = 0.96-1.38, P = .12), gender (RR = 0.95; 95% CI = 0.83-1.08, P = .44), tumor size (RR = 1.11, 95% CI = 0.85-1.44, P = .44), tumor site (RR = 1.01, 95% CI = 0.88-1.16, P = .84), or mucinous component (RR = 0.83, 95% CI = 0.60-1.14, P = .24) in CRC.ConclusionOur findings indicated that high MUC1 expression represents a marker of poor prognosis in CRC. Meanwhile, elevated MUC1 expression was associated with advanced TNM stage, greater depth of invasion, and lymph node metastasis.
| S-EPMC6831235 | biostudies-literature
Project description:BackgroundThe prognostic value of HIFs in colorectal cancer was evaluated in a large number of studies, but the conclusions were inconclusive. Meanwhile, clinicopathologic differences of HIF-1? and HIF-2? were rarely compared in recent studies.MethodologyIdentical search strategies were used to search relevant literatures in the PubMed and Web of Science databases. The prognostic significances and clinicopathological differences of HIFs in CRC were analyzed.Principal findingsA total of 23 studies comprising 2984 CRC patients met the inclusion criteria. The results indicated that overexpressed HIFs were significantly associated with increase of mortality risk, including overall survival (OS) (HR 2.06 95%CI 1.55-2.74) and disease free survival (HR 2.84, 95%CI 1.87-4.31). Subgroup analysis revealed that both overexpressed HIF-1? and HIF-2? had correlations with worse prognosis. The pooled HRs were 2.01 (95% CI: 1.55-2.6) and 2.07(95% CI: 1.01-4.26). Further subgroup analysis on HIF-1? was performed by study location, number of patients, quality score and cut-off value. The results showed that HIF-1? overexpression was significantly associated with poor OS, particularly in Asian countries (HR 2.3, 95% CI: 1.74-3.01), while not in European or other countries. In addition, overexpression of HIF-1? was closely related with these clinicopathological features, including Dukes' stages (OR 0.39, 95% CI: 0.17-0.89), UICC stages (OR 0.42 95% CI: 0.3-0.59), depth of invasion (OR 0.71, 95% CI: 0.51-0.99), lymphnode status (OR 0.49, 95% CI: 0.32-0.73) and metastasis (OR 0.29, 95% CI: 0.11-0.81). While overexpression of HIF-2? was only associated with grade of differentiation (OR 0.48, 95% CI: 0.29-0.81).ConclusionsThis study showed that both HIF-1? and HIF-2? overexpression were associated with an unfavorable prognosis. HIF-1? overexpression seemed to be associated with worse prognosis in Asian countries. Additionally, HIF-1? and HIF-2? indicated distinct clinicopathologic features.
| S-EPMC3855620 | biostudies-literature
Project description:CD166 has been identified as an important cancer stem cell (CSC) marker in colorectal cancer (CRC). The purpose of our study was to investigate the relationship between CD166 expression and clinical features and to examine the role of CD166 expression on the survival of patients with CRC. A total of 15 studies with 3,332 cases were identified in this meta-analysis. The pooled OR indicated that CD166 expression was significantly higher in CRC than in colonic adenomas or normal colonic mucosa (OR = 3.48, P = 0.002 and OR = 55.13, P = 0.017, respectively). CD166 expression was found to be negatively correlated with vascular invasion (OR = 0.75, P = 0.017), but it was not associated with gender, tumor location, lymph node status, distant metastasis, clinical stage, T classification or tumor differentiation. Meanwhile, CD166 expression was not associated with the prognosis of overall survival (OS) (HR = 1.20, 95% CI = 0.45-3.22, P = 0.72) in multivariate regression analysis. One study reported that CD166 expression may be a predictor of survival in stage II CRC patients using multivariate logistic regression analysis (OS: OR = 9.97, P = 0.035; disease-specific survival: OR = 29.02, P = 0.011). Our findings suggest that CD166 expression may be correlated with CRC carcinogenesis and a decreased risk of vascular invasion, and it may become a predictive biomarker of survival for stage II CRC patients, but additional studies with large sample sizes are essential to validate the prognostic and predictive values of CD166 expression.
| S-EPMC5610009 | biostudies-literature
Project description:BackgroundThe reliability of MUC2 as a prognostic marker in colorectal cancer (CRC) is controversial. This study evaluated the association between MUC2 expression levels in CRC tissues and prognosis.MethodsThe PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc (CBMdisc), Wanfang Database, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies exploring the relationship between MUC2 expression in CRC tissues and overall survival (OS). Pooled hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the associations between MUC2 expression levels and prognosis and MUC2 expression levels and CRC clinicopathological characteristics, respectively.ResultsThe meta-analysis included 11 studies (2619 patients). Low MUC2 expression level was significantly associated with poor OS (HR, 1.67; 95% CI, 1.43-1.94; P < 0.00001) and disease-free survival (DFS)/recurrence-free survival (RFS) (HR, 1.60; 95% CI, 1.21-2.12; P = 0.001) in patients with CRC. Low MUC2 expression level was associated with advanced TNM stage (RR, 1.42; 95% CI, 1.26-1.60; P < 0.00001), lymph node metastasis (RR, 1.41; 95% CI, 1.25-1.60; P < 0.00001), lymphatic invasion (RR,1.64; 95% CI, 1.26-2.12; P = 0.0002), rectal tumor site (RR, 1.26; 95% CI, 1.09-1.46; P = 0.001), and large tumor size (RR,1.32; 95% CI, 1.02-1.70; P = 0.03). There were no associations between low MUC2 expression level and gender, histological grade, depth of invasion, and distant metastasis.ConclusionThe low levels of MUC2 in CRC tissues are poor prognostic factor independent of stage or other well-recognized markers of later-stage disease. Large well-designed cohort studies are required to validate MUC2 as a biomarker for poor prognosis in CRC.
| S-EPMC6008766 | biostudies-literature
Project description:BackgroundCirculating cell-free DNA (cfDNA) is a promising candidate biomarker for detection, monitoring and survival prediction of colorectal cancer (CRC). However, its prognostic significance for patients with CRC remains controversial. To derive a precise estimation of the prognostic significance of cfDNA, a meta-analysis was performed.MethodsWe made a systematic search in data base of the Science Citation Index Embase and Pubmed for studies reporting prognostic data of cfDNA in CRC patients. The data of cfDNA on recurrences-free survival (RFS) and overall survival (OS) were extracted and measured in hazard rates (HRs) and 95% confident intervals (CIs). Subgroup analyses were carried out as well. Finally, the meta-analysis is accompanied with nine studies including 19 subunits.ResultsThe pooled HRs with 95% CIs revealed strong associations between cfDNA and RFS (HR [95%CI]=2.78[2.08-3.72], I(2)=32.23%, n=7) along with OS (HR [95%CI]=3.03[2.51-3.66], I(2)=29.24%, n=12) in patients with CRC. Entire subgroup analyses indicated strong prognostic value of cfDNA irrespective tumor stage, study size, tumor markers, detection methods and marker origin.ConclusionsAll the results exhibits that appearance of cfDNA in blood is an indicator for adverse RFS and OS in CRC patients.
| S-EPMC4911878 | biostudies-literature
Project description:CD44 is a marker of cancer stem-like cells in renal cell carcinoma (RCC). However, the prognostic value of CD44 in RCC remains controversial. This study evaluated the correlation of CD44 expression with the clinicopathological features of RCC through a meta-analysis. We systematically searched PubMed, ISI Web of Science and Embase for relevant studies until February 2015. We collected and analysed data on clinical stage, Fuhrman grade, microvascular invasion, recurrence, five-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Twenty studies involving 1672 patients satisfied the inclusion criteria. Results showed that high CD44 expression in RCC was a poor prognostic marker for five-year OS (RR?=?0.69, 95% CI 0.60-0.78) in a fixed-effects model and for five-year DSS (RR?=?0.46, 95% CI 0.27-0.80) and five-year DFS (RR?=?0.63, 95% CI 0.43-0.93) in a random-effects model. CD44 expression also correlated with Furhman grade (RR?=?0.61, 95% CI 0.48-0.77), tumour recurrence (RR?=?7.42, 95% CI 3.74-14.70) and MVI (Microvascular invasion) (RR?=?3.63, 95% CI 1.97-6.71). This meta-analysis suggests that CD44 is a prognostic marker in RCC. High CD44 expression correlates with high Fuhrman grade, recurrence, MVI and poor prognosis.
| S-EPMC4541415 | biostudies-literature
Project description:Background:The relationship between pretreatment C-reactive protein to albumin ratio (CAR) and colorectal cancer (CRC) prognosis has been extensively studied in various tumors. However, little is known on CAR and its association with prognosis in CRC. This study aims to investigate the prognostic value of pretreatment CAR in CRC. Methods:We conducted a systematic search of MEDLINE, EMBASE, and Cochrane Library databases for eligible studies evaluating the associations of CAR with survival and/or clinicopathology of CRC. Overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and clinicopathological features were synthesized and compared. Results:Nine studies including 3431 patients were analyzed in this meta-analysis. Pooled results showed that elevated pretreatment CAR was associated with poor OS (pooled hazards ratio [HR]: 2.18, 95% confidence interval [CI]: 1.70-2.78, P < .001) and DFS/RFS (pooled HR: 2.36, 95% CI: 1.40-3.98, P < .001). Moreover, elevated pretreatment CARs were correlated with male patients, large tumor diameter, late III-IV tumor node metastasis stage tumors, high serum carcinoembryonic antigen and carbohydrate antigen 19-9, and presence of lymphatic invasion and venous invasion. Conclusion:Elevated pretreatment CAR could be an adverse prognostic indicator in patients with CRC.
| S-EPMC6868585 | biostudies-literature