Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early ...diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation.
Proteomic analysis revealed 119 and 166 proteins for patients in stages I-II and III-IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (
< 0.01) for distinguishing stages I-II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression.
The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.
We sought to assess the prognostic value of variant histology in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.
We searched PubMed®, Web of Science™, Cochrane ...Library and Scopus® databases in May 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with upper tract urothelial carcinoma with or without variant histology. Formal meta-analyses were performed for these outcomes.
We identified 32 studies with 16,052 patients, including 26 studies with 12,865 patients that were eligible for the meta-analysis. Variant histology was associated with poor outcomes in terms of cancer specific (pooled HR 2.00, 95% CI 1.57 to 2.56), overall (pooled HR 1.76, 95% CI 1.51 to 2.04) and recurrence-free survival (pooled HR 1.64, 95% CI 1.42 to 1.89). Subgroup analyses revealed that micropapillary (pooled HR 3.02, 95% CI 1.71 to 5.34), and squamous and/or glandular variant histologies (pooled HR 1.48, 95% CI 1.14 to 1.92) were also associated with poor cancer specific survival.
Variant histology in patients with upper tract urothelial carcinoma is associated with an increased risk of cancer specific and overall mortality and disease recurrence. Furthermore, variant histology was independently associated with cancer specific survival in the micropapillary, and squamous and/or glandular variant histology subgroups. It may be useful to incorporate variant histology into prognostic tools that help guide patients and physicians in selecting appropriate treatment strategies for upper tract urothelial carcinoma.
A novel HPLC-ESI-MS/MS method for simultaneous gonadotropin-releasing hormone (GnRH) analogs and somatostatin analog quantitation was developed and validated. The developed method was successfully ...applied to pharmacokinetic studies. The sample preparation process included solid-phase extraction (SPE). Effective chromatographic separation of the analytes and internal standard (dalargin) was achieved with a C18 column, using a gradient elution with two mobile phases: 0.1%
/
formic acid (aqueous solution) and 0.1%
/
formic acid (acetonitrile solution). The linearity of the method was demonstrated within a concentration range of 0.5-20 ng/mL, with correlation coefficients between 0.998-0.999 for goserelin, buserelin, triptorelin, and octreotide, respectively. The relative standard deviation (RSD, %) values for method accuracy and precision did not exceed 20% at the lower level of quantitation (LLOQ) or 15% at other concentration levels.
We assessed the prognostic value of sex differences in upper tract urothelial carcinoma and urothelial carcinoma of the bladder treated with radical surgery.
The PubMed®, Web of Science®, Cochrane ...Library and Scopus® databases were searched in July 2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies were deemed eligible if they compared overall, cancer specific, and recurrence-free survival in patients with upper tract urothelial carcinoma and urothelial carcinoma of the bladder. Formal meta-analyses were performed for these outcomes according to sex differences.
Overall 66 studies with 100,389 patients with urothelial carcinoma of the bladder and 40 studies with 39,759 patients with upper tract urothelial carcinoma were eligible for review and meta-analysis. Female patients with urothelial carcinoma of the bladder were associated with worse cancer specific survival (pooled HR 1.20, 95% CI 1.10-1.31), overall survival (pooled HR 1.03, 95% CI 1.01-1.05) and recurrence-free survival (pooled HR 1.13, 95% CI 1.02-1.25). In contrast, those with upper tract urothelial carcinoma were not associated with cancer specific survival (pooled HR 0.94, 95% CI 0.89-1.00), overall survival (pooled HR 0.98, 95% CI 0.95-1.01) and recurrence-free survival (pooled HR 0.90, 95% CI 0.78-1.03).
Sex is associated with cancer specific mortality, overall mortality and disease recurrence in urothelial carcinoma of the bladder but not in upper tract urothelial carcinoma. Given the genetic and social differences between the sexes, sex differences may represent a key factor in the clinical decision making process.
Purpose
To assess the prognostic value of alkaline phosphatase in patients with hormone-sensitive prostate cancer.
Methods
A systematic review and meta-analysis was performed using the PUBMED, Web of ...Science, Cochrane Library, and Scopus in April 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared hormone-sensitive prostate cancer patients with high vs. low alkaline phosphatase to determine its predictive value for overall survival, cancer-specific survival, and progression-free survival. We performed a formal meta-analysis of these outcomes.
Results
42 articles with 7938 patients were included in the systematic review and 28 studies with 5849 patients for the qualitative assessment. High alkaline phosphatase was associated with worse overall survival (pooled HR 1.72; 95% CI 1.37−2.14) and progression-free survival (pooled HR 1.30; 95% CI 1.10−1.54). In subgroup analyses of patients with “high-volume” and “low-volume”, alkaline phosphatase was associated with the overall survival (pooled HR 1.41; 95% CI 1.21−1.64 and pooled HR 1.64; 95% CI, 1.06−2.52, respectively).
Conclusions
In this meta-analysis, elevated serum levels of alkaline phosphatase were associated with an increased risk of overall mortality and disease progression in patients with hormone-sensitive prostate cancer. In contrast, those were not associated with an increased risk of cancer-specific mortality. Alkaline phosphatase was independently associated with overall survival in both patients with “high-volume” and “low-volume” hormone-sensitive prostate cancer. Alkaline phosphatase may be useful for being integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision making process.
PURPOSE OF REVIEWConventional transurethral resection of bladder tumor (cTURBT) is the standard approach to the diagnosis and treatment of nonmuscle invasive bladder cancer. However, it suffers from ...inherent limitations such as insufficient assessment of resection depth and the need for intravesical tumor fragmentation that hampers histopathological evaluation. We summarize recent clinical data on en bloc resection of bladder tumor (ERBT), a method that promises to overcome these limitations.
RECENT FINDINGSThe PubMed/Medline databases were searched for reports on ERBT focusing on trends in the last 2 years. ERBT provides greater resection quality, making up to 95% of detrusor muscle available for pathological evaluation. ERBT also allows detection of the muscularis mucosae thus facilitating T1 substaging. Available data demonstrate no significant difference in perioperative morbidity. No conclusions can be drawn on the impact of either modality on tumor recurrence and progression, as the available data is too underpowered.
SUMMARYERBT is gaining acceptances as there is increasing evidence that it improves the quality of resected specimens. There seems to be no difference in perioperative morbidity between ERBT and cTURBT. The impact of ERBT on important endpoints such as recurrence and progression remains to be fully elucidated in further studies.
Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified ...an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies.
We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I
statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months).
A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months).
Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.
The purpose of this study was to assess the prognostic value of lactate dehydrogenase (LDH) in patients with metastatic prostate cancer (PC). A systematic review and meta-analysis was performed in ...March 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with PC with high versus low LDH to determine the predictive value of LDH for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We performed a formal meta-analysis for both OS and PFS. A total of 59 articles with 14,851 patients were included in the systematic review and 45 studies with 12,224 patients for the qualitative assessment. High LDH was associated with both worse OS (pooled hazard ratio HR, 2.07; 95% confidence interval CI, 1.75-2.44) and PFS (pooled HR, 1.08; 95% CI, 1.01-1.16). In subgroup analyses of both patients with castration-resistant prostate cancer (CRPC) and those with hormone-sensitive prostate cancer (HSPC), LDH was associated with OS (pooled HR, 2.02; 95% CI, 1.69-2.42 and pooled HR, 2.25; 95% CI, 1.78-2.84, respectively). In patients with CRPC, LDH was associated with OS in those treated with docetaxel systemic chemotherapy and androgen receptor–axis-targeting agents (pooled HR, 2.03; 95% CI, 1.37-3.00 and pooled HR, 1.79; 95% CI, 1.25-2.57, respectively). Elevated serum levels of LDH were associated with an increased risk of mortality and progression in patients with metastatic PC. LDH was independently associated with OS in both patients with CRPC and HSPC. LDH could be integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision-making process.
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•Systematic approach realizes common features between related and unrelated diseases.•Neural network can use both meaningful and unassigned mass spectrometry-based data.•Convolutional ...neural network discriminates closely related phenotypes.•Neural network suggests comorbidity between schizophrenia and oncophenotypes.
The association between cancer risk and schizophrenia is widely debated. Despite many epidemiological studies, there is still no strong evidence regarding the molecular basis for the comorbidity between these two pathological conditions. The vast majority of assays have been performed using clinical records of schizophrenic patients or those undergoing cancer treatment and monitored for sufficient time to find shared features between the considered conditions. We performed mass spectrometry-based proteomic and metabolomic investigations of patients with different cancer phenotypes (breast, ovarian, renal, and prostate) and patients with schizophrenia. The resulting vast quantity of proteomic and metabolomic data were then processed using systems biology and one-dimensional (1D) convolutional neural network (1DCNN) machine learning approaches. Traditional systematic approaches permit the segregation of schizophrenia and cancer phenotypes on the level of biological processes, while 1DCNN recognized “signatures” that could segregate distinct cancer phenotypes and schizophrenia at the comorbidity level. The designed network efficiently discriminated unrelated pathologies with a model accuracy of 0.90 and different subtypes of oncophenotypes with an accuracy of 0.94. The proposed strategy integrates systematic analysis of identified compounds and application of 1DCNN model for unidentified ones to reveal the similarity between distinct phenotypes.
Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies ...are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (±3.8%) and 1.7 mL min−1, respectively, while 99% (±0.7%) of sperm cells were disposed of. The introduced approach was further tested in a clinical setting by collecting and processing SF samples of PCa patients. The yield of isolated CTCs measured as high as 613 cells per SF sample in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC numbers with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise in the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.
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