Prognostic role of high cathepsin D expression in breast cancer: a systematic review and meta-analysis.
ABSTRACT: Background:High cathepsin D has been associated with poor prognosis in breast cancer; however, the results of many studies are controversial. Here, we assessed the association between high cathepsin D levels and worse breast cancer prognosis by conducting a meta-analysis. Methods:A comprehensive search strategy was used to search relevant literature in PUBMED and EMBASE by September 2018. The meta-analysis was performed in Review Manager 5.3 using hazard ratios (HRs) with 95% confidence intervals (CIs). Results:A total of 15,355 breast cancer patients from 26 eligible studies were included in this meta-analysis. Significant associations between elevated high cathepsin D and poor overall survival (OS) (HR?=?1.61, 95% CI: 1.35-1.92, p?
Project description:Various studies have evaluated the significance of PTEN (phosphatase and tensin homolog deleted from chromosome 10) expression in breast cancer, but their results remain controversial. We conducted a meta-analysis to evaluate the associations of PTEN expression with clinicopathological characteristics and prognosis in breast cancer. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to identify relevant publications. The associations between PTEN expression and clinicopathological parameters, disease-free survival (DFS), and overall survival (OS) were then assessed via meta-analyses of odds ratio (ORs) and hazard ratio (HRs) with 95% confidence intervals (CIs). Based on 27 studies involving 10,231 patients, the pooled results revealed that PTEN loss was significantly more common in breast cancer than in normal tissues (OR = 12.15, 95% CI = 6.48-22.79, P < 0.00001) and that PTEN loss had clear associations with larger tumor size (> 2 cm, OR = 0.62, 95% CI = 0.48-0.82, P = 0.0006), lymph node metastasis(OR = 0.61, 95% CI = 0.45-0.82, P = 0.0001), later TNM stage(stage III-IV, OR = 0.55, 95% CI = 0.35-0.86, P = 0.009), poor differentiation(OR = 0.37, 95% CI = 0.24-0.59, P < 0.0001), and the highly aggressive triple-negative phenotype (OR = 1.62, 95% CI = 1.23-2.12, P = 0.0005). Moreover, patients with PTEN loss exhibited significantly worse DFS and OS(HR = 1.63, 95% CI = 1.04-2.22, P < 0.00001; HR = 1.41, 95% CI = 1.08-1.73, P < 0.0001; respectively). In conclusion, PTEN loss might predict more aggressive behavior and worse outcomes in patients with breast cancer.
Project description:Inflammation and cancer are closely related to each other. As a parameter that can reflect inflammation and host immune reaction, elevated blood neutrophil to lymphocyte ratio (NLR) has been confirmed to be correlated with poor prognosis in a variety of cancers. However, this remains controversial in breast cancer. Thus, we performed this updated meta-analysis to further clarify whether high NLR could be a predictor of survival in breast cancer patients.We searched on PubMed Database and Cochrane Library. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival were used as outcome events, and hazard ratio (HR) was chosen as the parameter to evaluate the correlation.Eighteen eligible studies were involved in this meta-analysis. The synthesized analysis demonstrated that elevated NLR was associated with poor DFS [HR?=?1.72, 95% confidence interval (95% CI)?=?1.30-2.27], OS (HR?=?1.87, 95% CI?=?1.41-2.48), and cancer-specific survival (HR?=?2.09, 95% CI?=?1.04-4.21). The correlation was stronger in triple-negative breast cancer (TNBC) (OS: HR?=?2.58, 95% CI?=?1.63-4.06; DFS: HR?=?3.51, 95% CI?=?1.97-6.24).Higher NLR was correlated to poor prognosis of breast cancer patients. As a clinical parameter that we can easily obtain, NLR might be a potential predictor in patients' survival to assist with physicians' treatment decisions.
Project description:Purpose: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets. Methods: We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 158 TN tumors (54 AA) from The Cancer Genome Atlas (TCGA). Meta-analyses were performed to obtain summary estimates by combining TCGA and Detroit AA cohort results. Results: In the Detroit AA cohort, CLCA2 [Hazard ratio (HR)=1.56, 95% confidence interval (CI) 1.31-1.86, nominal p=5.1x10-7, FDR p=0.014], SPIC [HR=1.47, 95%CI 1.26-1.73, nominal p=1.8x10-6, FDR p=0.022], and MIR4311 [HR=1.57, 95% CI 1.31-1.92, nominal p=2.5x10-5, FDR p=0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. Meta-analysis with TCGA data showed that CLCA2 and SPIC were associated with overall survival for TNBC among AA women. Conclusions: We identified three potential prognostic markers for TNBC in AA women, for which SPIC may be an AA-specific prognostic marker. Overall design: 226 RNA samples from FFPE triple negative breast tumors. No replicates or control included
Project description:Numerous studies have investigated the prognostic role of YKL-40 in breast cancer, but yielded inconsistent results. To derive a more precise evaluation, relevant publications assessing the association between YKL-40 expression and clinical outcome of breast cancer patients were electronically searched and identified. A combined analysis of included studies was performed using fixed- or random-effect model to calculate the pooled hazard ratio (HR) or odds ratio(OR) and 95% confidence interval (95%CI) for the assessment of the association. Ten eligible studies involving 1250 patients were ultimately included in the meta-analysis. Overall, the pooled analysis showed that elevated YKL-40 expression was significantly associated with a poor overall survival(OS: HR=1.48, 95%CI= 1.11-1.97) and disease-free survival(DFS: HR=1.51, 95%CI= 1.10-2.07). The subgroup analysis by detection methods revealed an unfavorable OS in breast cancer patients with elevated YKL-40 expression evaluated by IHC(HR=1.39, 95%CI=1.12-1.71) but not by ELISA/RIA. Also, the stratification analysis by ethnicity showed a significant association between increased YKL-40 expression and shorter OS of breast cancer patients in western population(HR=1.51, 95%CI=1.03-2.21) as well as Asian population (HR=1.40, 95%CI= 1.05-1.86). Similarly, the subgroup analysis by detection methods revealed a significantly inferior DFS in breast cancer patients with increased YKL-40 expression disregarding the use of IHC(HR=2.02, 95%CI=1.47-2.79) or ELISA/RIA(HR=1.06, 95%CI= 1.02 -1.10). Additionally, increased YKL-40 expression was found to significantly correlate with larger tumor size (OR=2.38, 95%CI=1.41-4.05).The present meta-analysis indicate that elevated YKL-40 expression is associated with a poor prognosis in breast cancer patients. YKL-40 may serve as a promising predictive biomarker of prognosis of breast cancer.
Project description:<h4>Background</h4>Matrix metalloproteinases (MMPs) are regarded to be relevant to the prognosis of breast cancer. Numerous studies have confirmed the association between MMPs and tumor growth, invasion and metastasis in breast cancer. However, their prognostic values for survival in patients with breast cancer remain controversial. Hence, a meta-analysis was performed to clarify a more accurate estimation of the role of MMPs on prognosis of breast cancer patients.<h4>Method</h4>A systemic electronic search was conducted in PubMed, Embase and Web of science databases to identify eligible studies, which were associated with the relationship between MMPs and prognosis of breast cancer. The correlation in random-effect model was evaluated by using the hazard ratios (HRs) and 95% confidence intervals (CIs).<h4>Results</h4>A total of 28 studies covering 4944 patients were included for meta-analysis. A summary hazard ratio (HR) of all studies was calculated, as well as the sub-group HRs. The combined HRs calculated by either univariate or multivariate analysis both suggested that overexpression of MMPs had an unfavorable impact on overall survival (OS) (HR = 1.694, 95%CI: 1.347-2.129, P < 0.001; HR = 1.611, 95%CI: 1.419-1.830, P < 0.001, respectively). And the univariate analysis showed that patients with overexpression of MMPs had worse relapse-free survival (RFS) (HR = 1.969, 95%CI: 1.460-2.655, P < 0.001) in all eligible studies. In the sub-group analyses, HRs of MMP-9 positivity with poor OS were 1.794 (95%CI: 1.330-2.420, P < 0.001) and 1.709 (95%CI: 1.157-2.526, P = 0.007) which were separately evaluated by univariate and multivariate analysis. A small number of articles demonstrated that MMP-2 overexpression was not related with shorter OS (HR = 1.400, 95%CI: 0.610-3.029, P = 0.427). Four studies included in the OS analysis of MMPs expression in serum suggested that positive expression of serum MMPs may be an unfavorable factor (HR = 1.630, 95%CI: 1.065-2.494) for breast cancer patients. No publication bias was observed in the current meta-analysis.<h4>Conclusions</h4>Our findings suggested that MMPs overexpression (especially MMP-9, MMP-2, MMPs overexpression in serum) might indicate a higher risk of poor prognosis in breast cancer. Larger prospective studies are further needed to estimate the prognostic values of MMPs overexpression.
Project description:Accumulating evidence indicates that aberrant regulation of metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long noncoding RNA (lncRNA), plays a vital role in tumorigenesis. However, its association with breast cancer has not been systematically evaluated. In the current study, a meta-analysis was conducted to clarify the association between MALAT-1 and the prognosis and clinicopathological features of breast cancer. Relevant literature published in several databases was searched. Hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the effect of MALAT-1 expression on the survival outcomes and clinicopathological features of breast cancer. A total of 12 studies involving 4106 patients were identified. Pooled HR demonstrated that elevated MALAT-1 expression significantly predicted unfavorable overall survival (HR = 2.06, 95% CI: 1.66-2.56, P<0.0001) in patients with breast cancer. Subgroup analysis stratified by cancer type, sample size, and method of variance analysis also showed statistically significant associations. Additionally, the HR of patients with up-regulated MALAT-1 expression concerning disease-free survival (DFS), recurrence-free survival (RFS), and disease-specific survival (DSS) was 1.91 (95% CI: 1.53-2.39, P<0.0001). Further, elevated MALAT-1 expression was positively correlated with the progesterone receptor (PR) status (OR = 1.47, 95% CI: 1.18-1.82). Thus, MALAT-1 is a promising biomarker for predicting survival outcomes in patients with breast cancer.
Project description:BACKGROUND:MiRNAs are important regulators of different biological processes, including tumorigenesis. MiR-210 is a potential prognostic factor for survival in patients with cancer according to previous clinical researches. We conducted a systematic review and meta-analysis to summarize the significance of increased miR-210 expression in the prognosis of indicated cancers. METHODOLOGY/PRINCIPAL FINDINGS:The present systematic review and meta-analysis of 16 researches included 1809 patients with 7 different types of cancers from 7 countries, and aimed to explore the association between miR-210 expression and the survival of cancer patients. Over-expression of miR-210 may predict poor overall survival (OS, HR = 1.33, 95% CI: 0.85-2.09, P = 0.210), but the effect was not significant. While the predictive effect on disease-free survival (DFS, HR = 1.89, 95% CI: 1.30-2.74, P = 0.001), progression-free survival (PFS, HR = 1.20, 95% CI: 1.05-1.38, P = 0.007) and relapse-free survival(RFS, HR = 4.42, 95% CI: 2.14-9.15, P = 0.000) for patients with breast cancer, primary head and neck squamous cell carcinoma (HNSCC), renal cancer, soft-tissue sarcoma, pediatric osteosarcoma, bladder cancer or glioblastoma was certain. Subgroup analysis showed the limited predictive effect of over-expressed miR-210 on breast cancer OS (HR = 1.63, 95% CI: 0.47-5.67, P = 0.443), breast cancer DFS (HR = 2.03, 95% CI: 0.90-4.57, P = 0.088), sarcoma OS (HR = 1.24, 95% CI: 0.20-7.89, P = 0.818) and renal cancer OS (HR = 1.16, 95% CI: 0.27-4.94, P = 0.842). CONCLUSIONS/SIGNIFICANCE:This systematic review and meta-analysis suggests that miR-210 has a predictive effect on survival of patients with studied cancer types as indexed by disease-free survival, progression-free survival and relapse-free survival. While the predictive effect on overall survival, breast cancer overall survival, breast cancer disease-free survival, sarcoma overall survival and renal cancer overall survival was not statistically significant.
Project description:<h4>Background</h4>Anoctamin-1 (ANO1) plays a pivotal role in cancer progression. A meta-analysis was conducted to assess the potential prognostic role of ANO1 in cancers.<h4>Methods</h4>A total of 1760 patients from 7 eligible studies were included into the analysis. Pooled hazard ratios or odds ratios were extracted and calculated with a random-effects model, and analyses of heterogeneity bias were conducted.<h4>Results</h4>Our results showed that over expression of ANO1 was significantly correlated with poor overall survival in all cancers (HR?=?1.52; 95% CI: 1.19-1.92; P?=?.0006). Subgroup analysis indicated that there was a significant association between over expression of ANO1 and poor prognosis breast cancer (HR?=?3.24; 95% CI: 1.74-6.04), head and neck squamous cell carcinoma (HR?=?1.14; 95% CI: 1.00-1.30), esophageal squamous cell carcinoma (HR?=?1.93; 95% CI: 1.07-3.50), gastric cancer (HR?=?1.62; 95% CI: 1.12-2.34) and colorectal cancer (HR?=?1.38; 95% CI: 1.03-1.85). In addition, over expression of ANO1 was not associated with TNM stage, histological grade, lymph node metastasis, tumor size, age and gender. However, ANO1 was significantly associated with human epidermal growth factor receptor 2, but not associated with progesterone receptor or estrogen receptor in breast cancer.<h4>Conclusions</h4>Our results indicate that ANO1 can be a predictive factor for prognosis of cancer.
Project description:Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to be associated with tumor formation and invasion in many studies. However, the clinicopathological significance and prognosis of EMMPRIN in cancer patients remains inconclusive. Therefore, we conducted a meta-analysis to assess the predictive potential of EMMPRIN in various cancers. By searching Pubmed, Cochrane library database and web of science comprehensively, 39studies with 5739 cases were included in our meta-analysis. The results indicated that EMMPRIN overexpression was significantly associated with poor outcome of cancers (HR=2.46, 95% CI: 2.21-2.75, P<0.0001). In addition, a significant relation was found between EMMPRIN overexpression and clinicopathological features, such as tumor stage (T3+T4/ T1+T2, OR=1.87, 95% CI:1.64-2.12, P<0.0001), tumor differentiation (poor/ well+ moderate, OR=1.09, 95% CI:1.60-2.23, P<0.0001), clinical stage (III+IV /I +II, OR=1.96, 95% CI:1.69-2.27, P<0.0001) and nodal metastasis (positive/negative, OR=2.37, 95% CI:1.93-2.90, P<0.0001). However, the expression of EMMRIN was not significantly associated with tumor stage in cervical cancer (OR=1.35, 95%CI: 0.73-2.48, P=0.33). In conclusion, EMMPRIN overxepression is significantly associated with clinicopathological characteristics and prognosis of cancers. Thus, EMMPRIN may be regarded as a promising bio-marker in predicting the clinical outcome of patients in cancers and could be used as the therapeutic target during clinical practices.
Project description:Although many studies have discussed the association of abnormally expressed silent information regulator 1 (Sirt1) with the prognosis of patients with a variety of solid carcinomas, they failed to agree on whether excessive Sirt1 indicates a good or poor overall survival for the patients. We conducted the current meta-analysis to illustrate the prognostic value of Sirt1 in solid malignancies. Articles published before December 2016 were searched using Pubmed and Web of Science. The studies were selected for the meta-analysis based on certain criteria. A total of 7,369 cases from 37 studies were included, in which 48.6% of the patients overexpressed Sirt1. The overall survival (OS) and clinical features, such as age and TNM stage, were analyzed using RevMan 5.3 software. Sirt1 overexpression was significantly correlated with the OS (HR: 1.52, 95% CI: [1.23, 1.88], P = 0.0001), especially in liver cancer (HR: 1.78, 95% CI: [1.46, 2.18], P < 0.00001) and lung cancer (HR: 1.80, 95% CI: [1.06, 3.05], P = 0.03), which suggested that the overexpression of Sirt1 indicates poor prognosis of patients with solid cancers.