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The Combination of Computational and Biosensing Technologies for Selecting Aptamer against Prostate Specific Antigen.

ABSTRACT: Herein, we report a method of combining bioinformatics and biosensing technologies to select aptamers against prostate specific antigen (PSA). The main objective of this study is to select DNA aptamers with higher binding affinity for PSA by using the proposed method. Based on the five known sequences of PSA-binding aptamers, we adopted the functions of reproduction and crossover in the genetic algorithm to produce next-generation sequences for the computational and experimental analysis. RNAfold web server was utilized to analyze the secondary structures, and the 3-dimensional molecular models of aptamer sequences were generated by using RNAComposer web server. ZRANK scoring function was used to rerank the docking predictions from ZDOCK. The biosensors, the quartz crystal microbalance (QCM) and a surface plasmon resonance (SPR) instrument, were used to verify the binding ability of selected aptamer for PSA. By carrying out the simulations and experiments after two generations, we obtain one aptamer that can have the highest binding affinity with PSA, which generates almost 2-fold and 3-fold greater measured signals than the responses produced by the best known DNA sequence in the QCM and SPR experiments, respectively.

SUBMITTER: Hsieh PC

PROVIDER: S-EPMC5387809 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The Combination of Computational and Biosensing Technologies for Selecting Aptamer against Prostate Specific Antigen.

Hsieh Pi-Chou PC Lin Hui-Ting HT Chen Wen-Yih WY Tsai Jeffrey J P JJP Hu Wen-Pin WP

BioMed research international 20170328

Herein, we report a method of combining bioinformatics and biosensing technologies to select aptamers against prostate specific antigen (PSA). The main objective of this study is to select DNA aptamers with higher binding affinity for PSA by using the proposed method. Based on the five known sequences of PSA-binding aptamers, we adopted the functions of reproduction and crossover in the genetic algorithm to produce next-generation sequences for the computational and experimental analysis. RNAfol ...[more]

PMID: 28459059

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Project description:ImportanceThe 2012 US Preventive Services Task Force (USPSTF) Grade D recommendation against prostate-specific antigen (PSA) screening for all men has been controversial, with data documenting a shift to a higher stage of disease at diagnosis. The association between the Grade D recommendation and prostate cancer-specific mortality (PCSM) among contemporary cohorts, however, is unclear.ObjectiveTo evaluate PCSM rates between 1999 and 2019, comparing trends in rates before and after the change in the 2012 USPSTF screening guideline to assess its association with PCSM.ExposureThe 2012 USPSTF Grade D recommendation against PSA screening for all men.Design, setting, and participantsThis cross-sectional study used Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research maintained by the National Center for Health Statistics to collect data on cause of death for all individuals who died of prostate cancer in the US from 1999 to 2019. Analysis was performed from January to August 2021.Main outcomes and measuresTrends in PCSM rates were calculated from 1999 to 2012 and from 2014 to 2019, with a washout year of 2013, using linear regression, with year and binary indicator of pre-2013 and post-2013 status as interaction terms. Trends were further analyzed by age, race and ethnicity, urbanization category, and US Census region. Other measures included diagnosis of localized or metastatic prostate cancer and overall cancer mortality.ResultsA total of 618 095 patients died of prostate cancer in the US from 1999 to 2019. Age-adjusted PCSM decreased linearly at a rate of -0.273 per 100 000 population per year from 1999 to 2012 and stalled at a rate of -0.009 per 100 000 per year from 2014 to 2019 (P < .001). This finding was significant among men aged 60 years or older, especially among men aged 60 to 69 years, men aged 80 years or older, and among Black men. Men aged 60 to 64 years had a decreasing, age-adjusted PCSM rate of -0.0088 per 100 000 population per year prior to 2013 followed by an increasing rate of 0.0014 per 100 000 per year. Men aged 65 to 69 years had a decreasing, age-adjusted PCSM rate of -0.024 per 100 000 population per year prior to 2013 followed by an increasing rate of 0.0011 per 100 000 population per year. Men aged 80 years or older had the largest absolute difference between rates before and after 2013 compared with all other age groups, with a difference of 0.06 for men aged 80 to 84 years and 0.07 for men 85 aged years or older. Black men had a decreasing, age-adjusted PCSM rate of -0.700 per 100 000 population per year prior to 2013 followed by a flattened rate of -0.091 per 100 000 population per year. Changes were observed across races and ethnicities, urbanization categories, and US Census regions and were accompanied by increased diagnoses of metastatic disease, which are inconsistent with mortality trends across all malignant neoplasms.Conclusions and relevanceThis cross-sectional study using comprehensive PCSM data through 2019 demonstrated decreasing PCSM rates that flattened or increased after the 2012 USPSTF Grade D recommendation, suggesting that decreased PSA screening may be a factor associated with this change. This change was seen across ages, races and ethnicities, urbanization categories, and US Census regions. The updated 2018 USPSTF guideline supporting shared decision-making may reverse these trends in the coming years.

Project description:BackgroundTo investigate the role of Prostate Specific Antigen density (PSAD) in selecting prostate cancer patients for active surveillance (AS) and to determine a cutoff PSAD in identifying adverse pathological outcomes.MethodsData from 287 patients who underwent radical prostatectomy for prostate cancer were retrospectively reviewed. Six different AS protocols, the University of Toronto; Royal Marsden; John Hopkins; University of California San Francisco (UCSF); Memorial Sloan Kettering Cancer Center (MSKCC) and Prostate Cancer Research International: Active Surveillance (PRIAS), were applied to the cohort. Pre-operative demographics and pathological outcomes were analysed. Statistical analyses on the predictive factors of adverse pathological outcomes and significance of PSAD were performed. A cutoff PSAD with best balance between sensitivity and specificity in identifying adverse pathological outcome was determined.ResultsPSAD predicted adverse pathological outcomes better than Prostate Specific Antigen (PSA) level alone. The PSAD was significantly lower (0.12-0.13 ng/dl/ml) in protocols including PSAD (the John Hopkins and PRIAS) compared with the other four protocols not including PSAD as a selection criteria (0.21-0.25 ng/dl/dl, P = 0.00). PSAD predicted adverse pathological outcomes in all protocols not incorporating PSAD as an inclusion criteria (P = 0.00-0.02). By the receiver operator characteristics curve analysis, it was found that a PSAD level of 0.19 ng/ml/ml had the best balance between sensitivity and specificity in predicting pathological adverse disease (Area under curve = 0.63, P = 0.004).ConclusionPSAD is necessary in selecting prostate cancer patients for active surveillance. It predicts adverse pathological outcomes in patients eligible for active surveillance better than PSA level alone. A PSAD cutoff at 0.19 ng/ml/ml has the best balance between sensitivity and specificity in predicting pathological adverse disease. We recommend using AS protocol incorporating PSAD as a selection criteria (in particular the PRIAS protocol with a cutoff PSAD at 0.2 ng/ml/ml) when recruiting prostate cancer patients for AS.

Dataset Information

The Combination of Computational and Biosensing Technologies for Selecting Aptamer against Prostate Specific Antigen.

Publications

The Combination of Computational and Biosensing Technologies for Selecting Aptamer against Prostate Specific Antigen.

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