Background: Prostate cancer (PrC) is the second-most frequent cancer in men, its incidence is emerging globally and is the fifth leading cause of death worldwide. While diagnosis and prognosis of PrC have been studied well, the associated therapeutic biomarkers have not yet been investigated comprehensively. This systematic review and meta-analysis aim to evaluate the theragnostic effects of microRNA expressions on chemoresistance in prostate cancer and to analyse the utility of miRNAs as clinical theragnostic biomarkers. Methods: A systematic literature search for studies reporting miRNA expressions and their role in chemoresistance in PrC published until 2018 was collected from bibliographic databases. The evaluation of data was performed as per PRISMA guidelines for systematic review and meta-analysis. Meta-analysis was performed using a random-effects model using Comprehensive Meta-Analysis (CMA) software. Heterogeneity between studies was analysed using Cochran’s Q test, I2 and the Tau statistic. Quality assessment of the studies was performed using the Newcastle–Ottawa Scale (NOS) for the methodological assessment of cohort studies. Publication bias was assessed using Egger’s bias indicator test, Orwin and classic fail-safe N test, Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill methods. Findings: Out of 2909 studies retrieved, 79 studies were shortlisted and reviewed. A total of 17 studies met our eligibility criteria, from which 779 PrC patients and 17 chemotherapy drugs were examined, including docetaxel and paclitaxel. The majority of the drug regulatory genes reported were involved in cell survival, angiogenesis and cell proliferation pathways. We studied 42 miRNAs across all studies, out of which two miRNAs were found to be influencing chemosensitivity, while 21 were involved in chemoresistance. However, the remaining 19 miRNAs did not appear to have any theragnostic effects. Besides, the prognostic impact of the miRNAs was evaluated and had a pooled HR value of 1.960 with 95% CI (1.377–2.791). Interpretation: The observation of the current study depicts the significance of miRNA expression as a theragnostic biomarker in medical oncology. This review suggests the involvement of specific miRNAs as predictors of chemoresistance and sensitivity in PrC. Hence, the current systematic review and meta-analysis provide insight on the use of miRNA as PrC biomarkers, which can be harnessed as molecular candidates for therapeutic targeting.
Objective: High GATA2 expression has been associated with an increased risk of poor clinical outcomes after radical prostatectomy; however, this has not been studied in relation to risk of biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer after radical prostatectomy. Our aim was to evaluate the association between protein expression levels of GATA2 in primary prostate cancer tumour samples and the risk of BCR after SRT. Methods: 109 males who were treated with SRT were included. The percentage of cells with nuclear staining and GATA2 staining intensity were both measured. These two measures were multiplied together to obtain a GATA2 H-score (range 0–12) which was our primary GATA2 staining measure. Results: In unadjusted analysis, the risk of BCR was higher for patients with a GATA2 H-score >4 (hazard ratio = 2.04, p = 0.033). In multivariable analysis adjusting for SRT dose, pre-SRT PSA, pathological tumour stage and Gleason score, this association weakened substantially (hazard ratio = 1.45, p = 0.31). This lack of an independent association with BCR appears to be the result of correlations between GATA2 H-score >4 and higher pre-SRT PSA (p = 0.021), higher Gleason score (p = 0.044) and more severe pathological tumour stage (p = 0.068). Conclusion: Higher levels of GATA2 expression appear to be a marker of prostate cancer severity; however, these do not provide independent prognostic information regarding BCR beyond that of validated clinicopathological risk factors. Advances in knowledge: A higher GATA2 expression level appears to be correlated with known measures of prostate cancer severity and therefore is likely not an independent marker of outcome after SRT.
Introduction: Melanoma is a global disease that is predominant in Western countries. However, reliable data resources and comprehensive studies on the theragnostic efficiency of miRNAs in melanoma are scarce. Hence, a decisive study or comprehensive review is required to collate the evidence for profiling miRNAs as a theragnostic marker. This protocol details a comprehensive systematic review and meta-analysis on the impact of miRNAs on chemoresistance and their association with theragnosis in melanoma. Methods and analysis: The articles will be retrieved from online bibliographic databases, including Cochrane Review, EMBASE, MEDLINE, PubMed, Scopus, Science Direct, and Web of Science, with different permutations of ‘keywords’. To obtain full-text papers of relevant research, a stated search method will be used, along with selection criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 (PRISMA-P) standards were used to create this study protocol. The hazard ratio (HR) with a 95% confidence interval will be analyzed using Comprehensive Meta-Analysis (CMA) software 3.0. (CI). The pooled effect size will be calculated using a random or fixed-effects meta-analysis model. Cochran’s Q test and the I2 statistic will be used to determine heterogeneity. Egger’s bias indicator test, Orwin’s and the classic fail-safe N tests, the Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill calculation will all be used to determine publication bias. The overall standard deviation will be evaluated using Z-statistics. Subgroup analyses will be performed according to the melanoma participants’ clinicopathological and biological characteristics and methodological factors if sufficient studies and retrieved data are identified and available. The source of heterogeneity will be assessed using a meta-regression analysis. A pairwise matrix could be developed using either a pairwise correlation or expression associations of miRNA with patients’ survival for the same studies.
E18084 Background: Patient reported distress (PRD) is well recognized in cancer patients receiving treatment; regrettably, it is not always assessed in clinical practice. The failure to assess PRD might affect treatment, decrease patient’s quality of life (QoL), increase burden of suffering, and increases health care costs. Patients receiving palliative RT usually have a severe disease that requires an intervention to help ease symptom burden, especially pain. Methods: All RT patients in our clinic are asked to complete a PRD survey during treatment course. PRD forms consist of 30 categorical questions that assess distress subscales. Patients have the option to rate each question from 1 (low distress) to 5 (high distress). The survey also includes the National Comprehensive Cancer Network distress thermometer, which allows patients to rate overall distress level from 0 (no distress) to 10 (extreme distress). Patients’ records were retrospectively reviewed to abstract the needed information to assess survivorship. Results: 270 patients were included from March 2012-May 2015. Overall PRD was analyzed as a continuous and a categorical variable (low: 0-3, moderate: 4-6, high: 7-10). A correlation was noted in moderate distress category (RR: 1.51, P = 0.034), however, this was not noted in high distress category (RR: 1.25, P = 0.33). Age (P: 0.079) and primary site (P = 0.022) had the strongest correlation with survival. However, when combining patients with a moderate or high distress level, we observed a significantly increased risk of death compared to patients with low distress in single variable analysis (RR: 1.45, P = 0.046). This finding weakened slightly in multivariable analysis and was no longer quite significant (RR: 1.43, P = 0.066). Conclusions: This study suggests that 64% of patients receiving palliative RT were under moderate to severe distress that affected their QoL The results provide evidence that patients who have a score of 4 or higher on the patient reported distress level questionnaire have poorer survival after palliative RT. This finding was statistically significant without adjustment for potentially confounding variables, however was no longer quite significant after such multivariable adjustment.