Prognostic significance of Rab27 expression in solid cancer: a systematic review and meta-analysis.
ABSTRACT: Rab27 is an essential molecule of vesicle fusion and trafficking in exosome secretion process, which plays important roles in cancer progression and metastasis. Recent studies reported that Rab27 expression is also associated with cancer prognosis. Therefore, we performed a meta-analysis to reveal the prognostic significance of Rab27 expression in solid cancer. Data were extracted by searching on PubMed, Embase and Cochrane library until February 15 2020. Pooled hazard ratio (HR) with confidence interval (CI) was calculated to evaluate the association between Rab27 expression and survival in solid cancer. Ten studies with 1434 cancer patients were including for this meta-analysis. High expression of Rab27 was associated with poor survival (HR 2.67, 95% CI 1.52-4.69, p?=?0.001). High expression of Rab27A was significantly associated with lymph node metastasis (HR 1.53, 95% CI 1.00-2.34, p?=?0.048). High expression of Rab27B was significantly correlated with lymph node and distant metastasis (HR 2.15, 95% CI 1.56-2.95, p?
Project description:Background: Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway are a paradigm-shifting cancer therapy. Programmed cell death ligand 2 (PD-L2) is another ligand of PD-1, but its prognostic significance in solid cancer patients after surgery remains controversial. In this study, we aimed to reveal the prognostic implication of PD-L2 in solid tumors through a meta-analysis. Methods: We searched PubMed, Embase and the Cochrane library for studies reporting the relationship between PD-L2 expression and prognosis or clinicopathological features in solid cancer patients after surgery from inception to January 2018, with language restricted to English. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were determined to explore the prognostic value of PD-L2 expression. Odds ratios (ORs) were also calculated to investigate the relationship between PD-L2 expression and clinicopathological parameters. Results: Sixteen studies incorporating 3,533 patients were included in our meta-analysis. The pooled results revealed that PD-L2 overexpression was a weak negative predictor for overall survival (OS; HR = 1.38, 95% CI = 1.05-1.81, P = 0.021), as well as a strong predictor for poor disease-free survival (DFS)/progression-free survival (PFS) (HR = 1.44, 95% CI = 1.15-1.81, P = 0.001). In subgroup analyses, high PD-L2 expression revealed an unfavorable prognostic prediction for OS in hepatocellular carcinoma (HCC) (HR = 1.60, 95% CI = 1.12-2.29, P = 0.011) and for DFS/PFS in HCC (HR = 1.50, 95%CI = 1.04-2.16, P = 0.031) as well as clear cell renal cell carcinoma (HR = 1.45, 95% CI = 1.03-2.03, P = 0.033). Moreover, PD-L2 expression implied a weak trend toward the presence of lymphatic metastasis (presence vs. absence, OR = 1.61, 95% CI = 0.98-2.65, P = 0.061). Conclusion: High PD-L2 expression may promote tumor metastasis and predict unfavorable prognosis in solid cancer patients after surgery, especially in HCC.
Project description:HSF1 is reported to be overexpressed in various solid tumors and play a pivotal role in cancer progression. A meta-analysis was conducted to assess the potential prognostic role of HSF1 in patients with solid tumors.An extensive electronic search of three databases was performed for relevant articles. The pooled hazard ratios (HRs) or odds ratios with their corresponding 95% CI were calculated with a random-effects model. Heterogeneity and publication bias analyses were also conducted.A total of 3,159 patients from 10 eligible studies were included into the analysis. The results showed that positive HSF1 expression was significantly correlated with poor overall survival in all tumors (HR=2.09; 95% CI: 1.62-2.70; P<0.001). Subgroup analysis revealed that there was a significant association between HSF1 overexpression and poor prognosis in esophageal squamous cell carcinoma (ESCC) (HR=1.83; 95% CI: 1.21-2.77; P=0.004), breast cancer (BC) (HR=1.52; 95% CI: 1.24-2.86; P<0.001), hepatocellular carcinoma (HR=3.02; 95% CI: 1.77-5.18; P<0.001), non-small-cell lung cancer (HR=2.19; 95% CI: 1.20-3.99; P=0.01), and pancreatic cancer (HR=2.58; 95% CI: 1.11-6.03; P=0.03) but not in osteosarcoma (HR=1.58; 95% CI: 0.47-5.35; P=0.46). In addition, HSF1 overexpression was significantly associated with some phenotypes of tumor aggressiveness including TNM stage, histological grade, lymph node metastasis, and vascular invasion.HSF1 overexpression may prove to be an unfavorable prognostic biomarker for solid tumor patients.
Project description:Dysregulation of the long noncoding RNA antisense noncoding RNA in the INK4 locus (ANRIL) has been reported in various solid tumors. We performed a synthetic analysis to clarify the clinical value of ANRIL as a prognostic indicator in malignant tumors. Article collection was conducted using several electronic databases, including PubMed, Web of Science, Medline, OVID and Embase (up to July 14 2017). Thirteen original studies and 1172 total patients were included in the meta-analysis. There was a significant positive association between the high expression level of ANRIL and lymph node metastasis (OR = 4.77, 95% CI: 2.30-9.91, P < 0.001) by a random effects model (I2 = 73.2, P = 0.001) and negative association with poor grade cancer (OR = 3.44, 95% CI: 1.68-7.08) by a random-effects model (I2 = 77.9, P = 0.000). The results of the meta-analysis showed that overexpression of ANRIL is positively related to poor overall survival (OS) (pooled HR = 2.12, 95% CI: 1.78-2.53, P < 0.0001) by a fixed-effects model (I2 = 0%, P = 0.654) and poor disease-free survival (DFS) (HR = 2.10, 95% CI: 1.51-2.92, P < 0.001) by a fixed-effects model (I2 = 13.3%, P = 0.315) in human solid cancers. Statistically significant associations were also found with cancer type, analysis method, sample size, and follow-up time. In conclusion, ANRIL may serve as a novel biomarker for indicating lymph node metastasis and prognosis in human cancer.
Project description:BACKGROUND:The expression of the L-type amino acid transporter 1 (LAT1) plays a significant role in tumor progression. However, it remains unclear whether high LAT1 expression correlates with poor prognosis of solid tumor patients. Here, we conducted a meta-analysis to assess the potential of LAT1 in predicting the prognosis of tumor patients. METHODS AND FINDINGS:A total of 4,579 cases were analyzed from 35 qualified studies. In patients with solid tumors, elevated expression of LAT1 is associated with poor prognosis (overall survival [OS]: pooled hazard ratio (HR) = 1.848, 95% confidence interval (CI) = 1.620-2.108, P < 0.001; disease free survival [DFS]: pooled HR = 1.923, 95% CI = 1.585-2.333, P < 0.001; progression free survival [PFS]: pooled HR = 1.345, 95% CI = 1.133-1.597, P = 0.001). Furthermore, in subgroup analysis, we found an association between high LAT1 expression and poor OS in non-small cell lung cancer (HR = 1.554, 95% CI = 1.345-1.794, P < 0.001), pancreatic cancer (HR = 2.052, 95% CI = 1.613-2.724, P < 0.001) and biliary tract cancer (HR = 2.253, 95% CI = 1.562-3.227, P < 0.001). CONCLUSION:The results of this meta-analysis indicate the reliability and potential of using LAT1 expression as a predictive biomarker in solid cancers prior to treatment. However, further studies with larger sample sizes would be beneficial for fully evaluating the predictive value of LAT1 expression for clinical applications.
Project description:It was recently reported that increased SOX9 expression drives tumor growth and promotes cancer invasion during human tumorigenicity and metastasis. However, the prognostic value of SOX9 for the survival of patients with solid tumors remains controversial. The present meta-analysis was thus performed to highlight the link between dysregulated SOX9 expression and prognosis in cancer patients. A systematic literature search was conducted using the electronic databases PubMed, Web of Science and Embase to identify eligible studies. A random-effects meta-analytical model was employed to correlate SOX9 expression with overall survival (OS), disease-free survival (DFS) and clinicopathological features. In total, 17 studies with 3307 patients were eligible for the final analysis. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) suggested that high SOX9 expression has an unfavourable impact on OS (HR = 1.66, 95% CI 1.36-2.02, P < 0.001) and DFS (HR = 3.54, 95% CI 2.29-5.47, P = 0.008) in multivariate analysis. Additionally, the pooled odds ratios (ORs) indicated that SOX9 over-expression is associated with large tumor size, lymph node metastasis, distant metastasis and a higher clinical stage. Overall, these results indicated that SOX9 over-expression in patients with solid tumors might be related to poor prognosis and could serve as a potential predictive marker of poor clinicopathological prognosis factor.
Project description:Long non-coding RNA colon cancer-associated transcript-1 (CCAT1) is newly found to be related with diagnoses and prognosis of cancer. This meta-analysis was performed to investigate the relationship between CCAT1 expression and clinical parameters, including survival condition, lymph node metastasis and tumor node metastasis grade.The primary literatures were collected through initial search criteria from electronic databases, including PubMed, OVID Evidence-based medicine Reviews and others (up to May 12, 2017). Eligible studies were identified and selected by the inclusion and exclusion criteria. Data was extracted and computed into Hazard ratio (HR) for the assessment of overall survival, subgroup analyses were prespecified based on the digestive tract cancer or others. Analysis of different CCAT1 expression related with lymph node metastasis or tumor node metastasis grade was conducted. Risk of bias was assessed by the Newcastle-Ottawa Scale.9 studies were included. This meta-analysis showed that high CCAT1 expression level was related to poor overall survival, the pooled HR was 2.42 (95% confidence interval, CI: 1.86-3.16; P < 0.001; fix- effects model), similarly in the cancer type subgroups: digestive tract cancer (HR, 2.42; 95% CI, 1.79-3.29; P < 0.001; fix- effects model) and others (HR, 2.42; 95% CI, 1.42-4.13; P = 0.001; fix- effects model). The analysis showed that high CCAT1 was strongly related to positive lymph node metastasis (Odds ratio, OR: 3.24; 95% CI, 2.04-5.16; P < 0.001; fix- effects model), high tumor node metastasis stage (OR, 3.87; 95% CI, 2.53-5.92; P < 0.001; fix- effects model).In conclusion, this meta-analysis revealed that CCAT1 had potential as a diagnostic and prognostic biomarker in various cancers.
Project description:Background: T cell immunoglobulin and mucin-domain containing molecule-3 (TIM-3), a novel emerging immune checkpoint molecule, was reported to express both on various kinds of immune cells and tumor cells. Many previous studies have investigated the prognostic significance of TIM-3 in cancer. However, the sample number from single study was limited and results remained controversial. Methods: We searched PubMed, Web of Science, and Embase databases for publications concerning TIM-3 expression in solid cancers up to March 2020. The correlations between TIM-3 and survival as well as clinical-pathological features were analyzed. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence interval (CI) were estimated by either fixed or random effects models. Results: A total of 3,072 patients were included in our meta-analysis. The result suggested that TIM-3 protein overexpression was relevant to poor overall survival (HR = 1.73, 95% CI = 1.39-2.15, P < 0.001). Moreover, TIM-3 was shown to be connected with lymph node metastasis (N+ vs. N-, OR = 1.59, 95% CI = 1.10-2.29, P = 0.013), tumor grade (G2-3 vs. G1, OR = 1.68, 95% CI = 1.21-2.34, P = 0.002), as well as PD-1 expression (PD-1high vs. PD-1low, OR = 3.26, 95% CI = 2.20-4.82, P < 0.001). In database test, significant correlations between high TIM-3 mRNA expression and poor overall survival for patients with non-small cell lung cancer and gastric cancer were observed (HR = 1.46, 95% CI = 1.23-1.72, P < 0.001; HR = 1.41, 95% CI = 1.12-1.77, P = 0.0038). Conclusion: Our meta-analysis highlights that TIM-3 has the potential to serve as a prognostic marker and a valuable therapeutic target in solid tumors.
Project description:Liver kinase B1 (LKB1) is a protein kinase that regulates the growth, integrity and polarity of mammalian cells. Recent studies have reported the prognostic value of decreased LKB1 expression in different tumors. However, the results of these studies remain controversial. Therefore, this meta-analysis was performed to more accurately estimate the role of decreased LKB1 in the prognostication of human solid tumors.A systematic literature search in the electronic databases PubMed, Embase, Web of Science and CNKI (updated to October 15, 2015) was performed to identify eligible studies. The overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and clinicopathological features data were collected from these studies. The hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and pooled with a random-effects models using Stata12.0 software.A total of 14 studies covering 1915 patients with solid tumors were included in this meta-analysis. Decreased LKB1 was associated with poorer OS in both the univariate (HR: 1.86, 95%CI: 1.42-2.42, P<0.001) and multivariate (HR: 1.55, 95%CI: 1.09-2.21, P = 0.015) analyses. A subgroup analysis revealed that the associations between decreased LKB1 and poor OS were significant within the Asian region (HR 2.18, 95%CI: 1.66-2.86, P<0.001) and obvious for lung cancer (HR: 2.16, 95%CI: 1.47-3.18, P<0.001). However, the articles that involved analyses of both RFS and DFS numbered only 3, and no statistically significant correlations of decreased LKB1 with RFS or DFS were observed in this study. Additionally, the pooled odds ratios (ORs) indicated that decreased LKB1 was associated with larger tumor size (OR: 1.60, 95%CI: 1.09-2.36, P = 0.017), lymph node metastasis (OR: 2.41, 95%CI: 1.53-3.78, P<0.001) and a higher TNM stage (OR: 3.35, 95%CI: 2.20-5.09, P<0.001).These results suggest that decreased LKB1 expression in patients with solid tumors might be related to poor prognosis and serve as a potential predictive marker of poor clinicopathological prognostic factors. Additional studies are required to verify the clinical utility of decreased LKB1 in solid tumors.
Project description:Recently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor.Eligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively. Subgroup analysis was also performed according to patients' ethnicities, tumor types, detection methods, and analysis types.Data from 21 included studies with 2532 patients were summarized. HK2 overexpression was significantly associated with worse OS (pooled HR = 1.90, 95% CI = 1.51-2.38, p < 0.001) and PFS (pooled HR = 2.91, 95% CI = 2.02-4.22, p < 0.001) in solid tumor. As to a specific form of cancer, the negative effect of HK2 on OS was observed in hepatocellular carcinoma (pooled HR = 2.06, 95% CI = 1.67-2.54, p < 0.001), gastric cancer (pooled HR = 1.72, 95% CI = 1.09-2.71, p = 0.020), colorectal cancer (pooled HR = 2.89, 95% CI = 1.62-5.16, p < 0.001), but not in pancreatic cancer (pooled HR = 1.13, 95% CI = 0.28-4.66, p = 0.864). No publication bias was found in the included studies for OS (Begg's test, p = 0.325; Egger's test, p = 0.441).In this meta-analysis, we identified that elevated HK2 expression was significantly associated with shorter OS and PFS in patients with solid tumor, but the association varies according to cancer type.
Project description:BACKGROUND:To guide the selection of treatments for spinal metastases, the expected survival time is one of the most important determinants. Few scoring systems are fully applicable for spinal metastasis secondary to prostate cancer (PCa). This study aimed to identify the independent factors to predict the overall survival (OS) of patients with spinal metastases from PCa. METHODS:The PubMed, Embase and CENTRAL were retrieved by two reviewers independently, to identify studies analyzed the prognostic effect of different factors in spinal metastasis from PCa. A systematic review and quantitative meta-analysis was conducted with hazard ratio (HR) and 95% confidence interval (95%CI) as the effect size. RESULTS:A total of 12 retrospective cohort studies (1566 patients) were eligible for qualitative synthesis and 10 for quantitative meta-analyses. The OS was significantly influenced by performance status, visceral metastasis, ambulatory status and time from PCa diagnosis in more than half of the available studies. The meta-analyses demonstrated that OS was significantly influenced by visceral metastasis (HR?=?2.24, 95%CI:1.53-3.27, p?<?0.001), pre-treatment ambulatory status (HR?=?2.64, 95%CI:1.82-3.83, p?<?0.001), KPS (HR?=?4.45, 95%CI:2.01-9.85, p?<?0.001), ECOG (HR?=?2.96, 95%CI:2.02-4.35, p?<?0.001), extraspinal bone metastasis (HR?=?2.04, 95%CI:1.13-3.68, p?=?0.018), time developing motor deficit (HR?=?1.57, 95%CI:1.30-1.88, p?<?0.001) and time from PCa diagnosis (HR?=?1.37, 95%CI:1.17-1.59, p?<?0.001). CONCLUSIONS:Visceral metastasis, ambulatory status, extraspinal bone metastasis, performance status, time developing motor deficit and time interval from primary tumor diagnosis were significantly associated with the OS for spinal metastasis from PCa. When selecting the treatment modality, clinicians should fully consider the patients' systematic status based on all potential prognostic factors. LEVEL OF EVIDENCE:I Meta-analysis.