scholarly journals Prognostic Value of Long Non-coding RNAs in Urological Malignancies: A Systematic Review, and Meta-Analysis

2021 ◽  
Vol 11 (1) ◽  
pp. 115-125
Author(s):  
Zeinab Bagheri ◽  
Mohammad-Hassan Arjmand

Background: Many studies have explored the potential roles of long non-coding RNAs (lncRNAs) in urological cancer (UC) progression. The clinical outcome and prognosis of UCs remain weak. Therefore, finding clinical prognostic markers is needed to improve therapeutic potential. The aim of this study was to consider the possible association between the lncRNAs expression with the survival time and clinical outcomes in patients with UC. Methods: A literature search was performed in several related databases to find eligible English papers published before 9 February 2021. Hazard ratios (HRs) with 95% CI were calculated to investigate the association between lncRNAs expression and overall survival in patients with UC. Results: A total of 46 studies, including 39 lncRNAs were identified. Results indicated that lncRNAs expression was significantly correlated with poor overall survival (OS) outcome in patients with UCs (HR: 1.923, 95% CI: 1.448-2.554, P<0.001). Also, we divided included studies into up-regulated and down-regulated subgroups according to lncRNAs expression. The results indicated a significant association with poor OS outcomes in both up-regulated (HR=2.546, 95% CI: 1.896-3.41, P<0.001) and down-regulated (HR=0.33, 95% CI: 0.22-0.49, P<0.001). Moreover, expression of lncRNAs was significantly associated with lymph node metastasis (LNM) (OR=0.25, 95% CI: 0.13-0.47, P<0.001) Conclusion: Abnormal expression of various lncRNAs is a potential novel marker for predicting the clinical outcomes of urological tumors.

2021 ◽  
Author(s):  
Yan-Hua Huang ◽  
Sun-Jun Yin ◽  
Yuan-Yuan Gong ◽  
Zhi-Ran Li ◽  
Qin Yang ◽  
...  

Aim: A comprehensive meta-analysis was carried out to evaluate the association between high PARP1 expression and clinical outcomes in diverse types of cancers. Materials & methods: The electronic databases for all articles about PARP1 expression and cancers were searched. Additionally, bioinformatics analysis was utilized to validate the results of the meta-analysis. Results: Fifty-two studies with a total of 7140 patients were included in the current meta-analysis. High PARP1 expression was found to be significantly associated with poor overall survival and recurrence in various cancers, which were further strengthened and complemented by the results of bioinformatic analysis. Furthermore, increased PAPR1 expression was also related to clinicopathological features. Conclusion: Our findings confirmed that PARP1 might be a promising biomarker for prognosis in human cancers.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Hailun Xie ◽  
Lishuang Wei ◽  
Shuangyi Tang ◽  
Jialiang Gan

Background. Recently, it has been reported that the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) is related to the prognosis of various cancers. The purpose of this systematic review and meta-analysis was to explore the prognostic value of pretreatment AAPR on clinical outcomes in cancer. Methods. PubMed, Web of Science, Cochrane Library, and Embase were systematically searched for relevant research before May 2020. Stata 12 was utilized to extract the data and the characteristics of each study and to generate a pooled hazard ratio (HR) and 95% confidence interval (CI) to assess the relationship between pretreatment AAPR and survival outcomes. Results. We included 16 eligible published articles involving 5,716 patients. We found that low pretreatment AAPR was associated with poor overall survival ( HR = 2.12 , 95% CI: 1.80–2.50, P < 0.001 ), cancer-specific survival ( HR = 2.89 , 95% CI: 1.46–5.71, P < 0.001 ), disease-free survival ( HR = 1.91 , 95% CI: 1.43–2.53, P < 0.001 ), and progression-free survival ( HR = 1.93 , 95% CI: 1.49–2.52, P < 0.001 ). However, there was no statistical relationship between pretreatment AAPR and recurrence-free survival, distant-metastasis-free survival, or locoregional relapse-free survival. The correlation between pretreatment AAPR and overall survival did not change significantly when possible confounders were stratified. The sensitivity analysis showed that this study was reliable. Conclusions. Low pretreatment AAPR was significantly associated with adverse clinical outcomes of cancer. Pretreatment AAPR could be a valuable noninvasive prognostic indicator for cancer.


2021 ◽  
Author(s):  
Sebastian Brandner ◽  
Alexandra McAleenan ◽  
Claire Kelly ◽  
Francesca Spiga ◽  
Hung-Yuan Cheng ◽  
...  

Abstract BACKGROUND The DNA repair protein O6 methylguanine-DNA methyltransferase (MGMT) causes resistance of tumour cells to alkylating agents. It is a predictive biomarker in high grade gliomas treated with temozolomide, however there is no consensus on which test method, methylation sites, and cut-off values to use. METHODS We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; where MGMT status was determined in tumour tissue, and assessed by one or more technique; and where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios. Two or more methods were compared in 32 independent cohorts with 3474 patients. RESULTS Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP. CONCLUSIONS We cannot draw strong conclusions about use of frozen tissue versus formalin-fixed paraffin embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and Pyrosequencing at CpG sites ranging from 72 to 95. A cut-off threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies. 190 studies were identified presenting hazard ratios from survival analysis in patients in which MGMT methylation was measured by one technique only.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A708-A708
Author(s):  
Pierre-Alain Bandinelli ◽  
Julie Cervesi ◽  
Clément Le Bescop ◽  
Renaud Buffet ◽  
Jean De Gunzburg ◽  
...  

BackgroundImmune checkpoint inhibitors (ICIs) have been shown to improve patients‘ clinical outcomes in a variety of cancers, but with variable efficacy. Prior research has also suggested that systemic antibiotic (ABX) exposure may impact the intestinal microbiota and result in suboptimal ICI treatment outcomes. Our team published a systematic review and meta-analysis showing that ABX use could indeed decrease the survival of patients diagnosed with non-small-cell lung cancer (NSCLC) and treated with ICIs.1 The present abstract aims at updating this meta-analysis by incorporating new studies that have been published in the period ranging from September 2019 to August 2020.MethodsMedline (through PubMed), the Cochrane Library and major oncology conferences proceedings were systematically searched to identify studies assessing the impact of ABX use on the clinical outcomes of NSCLC patients treated with ICIs. Studies were found eligible for inclusion when they mentioned a hazard ratio (HR) or Kaplan–Meier curves for overall survival (OS) or progression-free survival (PFS) based on antibiotic exposure. Pooled HRs for OS and PFS and HRs for OS and PFS according to different time windows for ABX exposure were calculated.Results6 eligible new studies were identified between September 2019 and August 2020 while 3 other studies were updated with new information. Altogether, 27 studies reported data for OS (6,436 patients, 826 of whom coming from new studies) and 24 for PFS (3,751 patients, 786 of whom coming from new studies). The pooled HR was 1.75 (95% confidence interval [CI]: 1.38–2.23) for OS and 1.57 (95% CI: 1.28–1.92) for PFS, confirming a significantly reduced survival in patients with NSCLC exposed to ABX. The detailed analysis in subgroups based on the time window of exposure (figure 1, figure 2) suggests that the deleterious effect of ABX is stronger when the exposition happens shortly before and after the initiation of the ICI treatment.Abstract 671 Figure 1Forest plot of hazard ratios for overall survival of patients diagnosed with NSCLC and exposed to antibiotics versus not exposed to antibiotics, according to the time window of antibiotic exposureAbstract 671 Figure 2Forest plot of hazard ratios for progression-free survival of patients diagnosed with NSCLC and exposed to antibiotics versus not exposed to antibiotics, according to the time window of antibiotic exposureConclusionsThe update of the meta-analysis confirms the previously reported deleterious effect of ABX on ICI treatment outcomes, taking into account the latest publications in the field. The topic deserves further research to uncover if the effect will stand with 1st line use of ICI together with chemotherapies and/or other approved combinations, elucidate the mechanisms at stake and improve care of patients.ReferencesLurienne L, Cervesi J, Duhalde L, de Gunzburg J, Andremont A, Zalcman G, et al. NSCLC immunotherapy efficacy and antibiotic use: a systematic review and meta-analysis. J Thorac Oncol 2020;15:1147–1159.


2020 ◽  
Vol 22 (3) ◽  
pp. 127-132
Author(s):  
A. S. Popova ◽  
M. Yu. Fedyanin ◽  
I. A. Pokataev ◽  
S. A. Tyulyandin

The method of liquid biopsy allows detection of circulating tumor DNA (ctDNA) in patient blood, but the clinical significance of this approach in pancreatic cancer is still unclear. In this regard, we have carried out a meta-analysis of the studies dedicated to the predictive significance of ctDNA in pancreatic cancer. Materials and methods.We carried out the search for the articles and abstracts in PubMed, ASCO and ESMO databases published before February 2020, containing data about the connection between ctDNA and the prognosis of pancreatic cancer. The exclusion criteria were the studies including 10 or less participating patients, absence of the data about the relative risk of mortality and/or progression, and the 95% confidence interval. The meta-analysis was carried out by using the Review Manager software (RevMan), Version 5.3. Results.There were no significant systematic errors associated with the publications. The presence of ctDNA in patient blood showed poor overall survival of patients (odds ratio OR 2.21, 95% confidence interval CI 1.35-3.33,p=0.001) regardless of the prevalence of the disease. In case of the resectable process, the detection of ctDNA in patient blood both before and after surgery was a factor of worse progression-free survival (OR 2.32, 95% CI 1.543.5,p0.001 and OR 3.06, 95% CI 1.635.76,р=0.0005 and overall survival (OR2.01, 95% CI 1.123.63,р=0,02 and OR 3.39, 95% CI 2.125.44,р0.00001, respectively). Conclusions.The detection of ctDNA in the bloodstream in pancreatic cancer patients is a factor of poor prognosis in both localized and advanced cancer. It is very important to make further prospective studies to develop the optimal protocol for detecting ctDNA in patient bloodstream.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ningning Zhang ◽  
Yushu Ouyang ◽  
Jianlan Chang ◽  
Ping Liu ◽  
Xiangyang Tian ◽  
...  

Background. Platinum-based chemotherapy plays an antitumor role by damaging DNA. X-ray repair crosscomplementing protein 1 (XRCC1) participates in DNA repair and thus affects the sensitivity to platinum drugs. Two polymorphisms of XRCC1, rs25487 (Arg399Gln) and rs1799782 (Arg194Trp), have been widely studied for the association with clinical outcomes of platinum-based chemotherapy in Asian patients with non-small-cell lung cancer (NSCLC), but the results remain inconclusive. Thus, we performed the present meta-analysis. Methods. Literature search was performed in PubMed, Web of Science, and EMBASE up to June 2019. Odds ratios (ORs) for objective response ratio (ORR), Cox proportional hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association strengths between XRCC1 polymorphisms and clinical outcomes. Comparisons were performed in homozygous, heterozygous, dominant, and recessive models. Results. Finally, a total of 23 studies involving 5567 patients were included in the meta-analysis. Compared to ArgArg of rs25487, GlnGln ( OR = 1.71 , 95% CI: 1.16-2.52, p = .007 , I 2 = 56.8 % ) and GlnArg ( OR = 1.23 , 95% CI: 1.07-1.40, p = .003 , I 2 = 29.0 % ) were associated with higher ORR. Meanwhile, GlnGln indicated a favorable OS ( HR = 0.60 , 95% CI: 0.40-0.88) and PFS ( HR = 0.64 , 95% CI: 0.46-0.90). We also found positive associations between rs1799782 and ORR in all comparison models with low between-study heterogeneity. The association strength increased with the number of variant alleles (TrpTrp vs. ArgArg: OR = 1.73 , 95% CI:1.31-2.27; TrpArg vs. ArgArg: OR = 1.28 , 95% CI: 1.06-1.55), suggesting a gene dosage effect. In addition, TrpTrp predicted a longer OS. Conclusion. Our results showed that rs25487 and rs1799782 of XRCC1 are potential markers to predict clinical outcomes of platinum-based chemotherapy in Asian patients with NSCLC.


BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e037614
Author(s):  
Xin Chen ◽  
Jing Li ◽  
Xunlei Zhang ◽  
Yushan Liu ◽  
Jindong Wu ◽  
...  

ObjectiveOur study aimed to evaluate the prognostic and clinicopathological significance of pretreatment mean platelet volume (MPV) on cancer by using meta-analysis of published studies.DesignMeta-analysis.Data sourcesRelevant studies available before 22 December 2019 were identified by searching MEDLINE, EMBASE.Eligibility criteriaAll published studies that assessed the prognostic and clinicopathological significance of pretreatment MPV on cancer were included.Data extraction and synthesisStudies were identified and extracted by two reviewers independently. The HR/OR and its 95% CIs of survival outcomes and clinicopathological parameters were calculated.ResultsA total of 38 eligible studies (41 subsets) with 9894 patients with cancer were included in the final meta-analysis. MPV level was not significantly associated with both overall survival (HR 0.98, 95% CI 0.84 to 1.14) and disease-free survival (HR 1.22, 95% CI 0.86 to 1.73) of patients with cancer. Neither advanced nor mixed-stage tumour patients showed significant association between MPV and overall survival (HR 1.36, 95% CI 0.96 to 1.94, HR 0.90, 95% CI 0.74 to 1.09). However, high MPV had the strongest relationship with poor overall survival (HR 2.01; 95% CI 1.08 to 3.41) in gastric cancer, followed by pancreatic cancer (HR 1.54; 95% CI 1.31 to 1.82). Whereas in the subgroup using receiver operating characteristic curve method to define cut-off values, low MPV was significantly related to poor overall survival (HR 0.78, 95% CI 0.64 to 0.95). In addition, MPV had no significant association with age (OR 0.96, 95% CI 0.90 to 1.02), sex (OR 1.04, 95% CI 1.00 to 1.09), depth of cancer invasion (OR 0.90, 95% CI 0.77 to 1.04) and tumour stage (OR 0.91, 95% CI 0.78 to 1.07).ConclusionsPretreatment MPV level is of no clearly prognostic significance in cancers and no significant association with clinicopathological parameters of patients with cancers.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2950
Author(s):  
Kayleigh Slater ◽  
Aisling B. Heeran ◽  
Sandra Garcia-Mulero ◽  
Helen Kalirai ◽  
Rebeca Sanz-Pamplona ◽  
...  

Metastatic uveal melanoma (UM) is a rare, but often lethal, form of ocular cancer arising from melanocytes within the uveal tract. UM has a high propensity to spread hematogenously to the liver, with up to 50% of patients developing liver metastases. Unfortunately, once liver metastasis occurs, patient prognosis is extremely poor with as few as 8% of patients surviving beyond two years. There are no standard-of-care therapies available for the treatment of metastatic UM, hence it is a clinical area of urgent unmet need. Here, the clinical relevance and therapeutic potential of cysteinyl leukotriene receptors (CysLT1 and CysLT2) in UM was evaluated. High expression of CYSLTR1 or CYSLTR2 transcripts is significantly associated with poor disease-free survival and poor overall survival in UM patients. Digital pathology analysis identified that high expression of CysLT1 in primary UM is associated with reduced disease-specific survival (p = 0.012; HR 2.76; 95% CI 1.21–6.3) and overall survival (p = 0.011; HR 1.46; 95% CI 0.67–3.17). High CysLT1 expression shows a statistically significant (p = 0.041) correlation with ciliary body involvement, a poor prognostic indicator in UM. Small molecule drugs targeting CysLT1 were vastly superior at exerting anti-cancer phenotypes in UM cell lines and zebrafish xenografts than drugs targeting CysLT2. Quininib, a selective CysLT1 antagonist, significantly inhibits survival (p < 0.0001), long-term proliferation (p < 0.0001), and oxidative phosphorylation (p < 0.001), but not glycolysis, in primary and metastatic UM cell lines. Quininib exerts opposing effects on the secretion of inflammatory markers in primary versus metastatic UM cell lines. Quininib significantly downregulated IL-2 and IL-6 in Mel285 cells (p < 0.05) but significantly upregulated IL-10, IL-1β, IL-2 (p < 0.0001), IL-13, IL-8 (p < 0.001), IL-12p70 and IL-6 (p < 0.05) in OMM2.5 cells. Finally, quininib significantly inhibits tumour growth in orthotopic zebrafish xenograft models of UM. These preclinical data suggest that antagonism of CysLT1, but not CysLT2, may be of therapeutic interest in the treatment of UM.


2019 ◽  
Vol 34 (2) ◽  
pp. 108-116
Author(s):  
Dan Zhang ◽  
Lizhen Dai ◽  
ZengXi Yang ◽  
XiChen Wang ◽  
Yin LanNing

Background: The prognostic value of Stathmin 1 (STMN1) in malignant solid tumors remains controversial. Thus, we conducted this meta-analysis to summarize the potential value of STMN1 as a biomarker for predicting overall survival in patients with solid tumor. Methods: We systematically searched eligible studies in PubMed, Web of Science, and EMBASE from the establishment date of these databases to September 2018. Hazard ratio (HR) and its 95% confidence interval (CI) was used to assess the association between STMN1 expression and overall survival. Results: A total of 25 studies with 4625 patients were included in this meta-analysis. Our combined results showed that high STMN1 expression was associated with poor overall survival in solid tumors (HR = 1.85, 95% CI 1.55, 2.21). In general, our subgroup and sensitivity analyses demonstrated that our combined results were stable and reliable. However, from the results of the subgroups we found that high STMN1 expression was not related to overall survival in colorectal cancer and endometrial cancer anymore, suggesting that much caution should be taken to interpret our combined result, and more studies with large sample sizes are required to further explore the prognostic value of STMN1 expression in the specific type of tumors, especially colorectal cancer and endometrial cancer. Conclusions: STMN1 could serve as a prognostic biomarker and could be developed as a valuable therapeutic target for patients with solid tumors. However, due to the limitations of the present meta-analysis, this conclusion should be taken with caution. Further studies adequately designed are required to confirm our findings.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Gaetan Des Guetz ◽  
Bernard Uzzan ◽  
Thierry Bouillet ◽  
Patrick Nicolas ◽  
Kader Chouahnia ◽  
...  

Background. Physical activity (PA) reduces incidence of colorectal cancer (CRC). Its influence on cancer-specific (CSS) and overall survival (OS) is controversial.Methods. We performed a literature-based meta-analysis (MA) of observational studies, using keywords “colorectal cancer, physical activity, and survival” in PubMed and EMBASE. No dedicated MA was found in the Cochrane Library. References were cross-checked. Pre- and postdiagnosis PA levels were assessed by MET. Usually, “high” PA was higher than 17 MET hour/week. Hazard ratios (HRs) for OS and CSS were calculated, with their 95% confidence interval. We used more conservative adjusted HRs, since variables of adjustment were similar between studies. When higher PA was associated with improved survival, HRs for detrimental events were set to <1. We used EasyMA software and fixed effect model whenever possible.Results. Seven studies (8056 participants) were included, representing 3762 men and 4256 women, 5210 colon and 1745 rectum cancers. Mean age was 67 years. HR CSS for postdiagnosis PA (higher PA versus lower) was 0.61 (0.44–0.86). The corresponding HR OS was 0.62 (0.54–0.71). HR CSS for prediagnosis PA was 0.75 (0.62–0.91). The corresponding HR OS was 0.74 (0.62–0.89).Conclusion. Higher PA predicted a better CSS. Sustained PA should be advised for CRC. OS also improved (reduced cardiovascular risk).


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