Evaluation of renal biomarkers, including symmetric dimethylarginine, following gentamicin-induced proximal tubular injury in the rat

Symmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days. Serum and urine renal biomarker evaluation including serum SDMA, hematologic and serum biochemical analysis, urinalysis, and histologic examination of kidney were performed. Prior to biologic validation, analytic validation of the SDMA immunoassay for rat serum was performed including assessment of assay accuracy, precision, analytical sensitivity, linearity, analyte stability, and interference testing. Among markers of excretory renal function SDMA and serum creatinine increased earliest and at the lowest gentamicin concentrations and were significantly increased in both the 50 mg/kg and the 100 mg/kg dosage levels in the 4 and 10-dose treatment groups compared to controls. Time- and dose-dependent increases were noted for all urinary biomarkers investigated in this study, with µALB being most responsive and OPN least responsive for detection of gentamicin-induced injury across dose levels and schedules investigated. The SDMA immunoassay met all set quality requirements assessed in analytical validation. This study is the first to investigate performance of serum SDMA as compared to other excretory renal function markers in a rat gentamicin acute toxicity model. In this study serum SDMA was an earlier biomarker for detection of gentamicin-induced toxicity than serum cystatin C, BUN, and creatinine clearance. The SDMA immunoassay provides a reliable commercially available assay for future renal investigations in rat models.

BIOM-11. THE PROGNOSTIC VALUE OF ROUTINE AND SPECIALIZED BLOOD TESTING IN GLIOBLASTOMA: A SYSTEMATIC REVIEW

BACKGROUND A combination of clinical characteristics, radiological findings and tissue markers is used in the assessment of glioblastoma prognosis and prediction of treatment response. The value of routine blood tests as a tool of prognosis has been a subject of debate. In addition to increased complication rate in subsequent resections and radiological uncertainty in treatment monitoring, there is a need to monitor tumor markers in a minimally invasive manner, as molecular characterization becomes more important in the management of glioblastoma. The objective of this review is to evaluate the prognostic value of any blood marker during the course of disease and treatment in glioblastoma. METHODS We researched Pubmed and Embase for clinical studies including cohort studies and randomized controlled trials that included at least 10 adult patients and blood testing during course of disease. We extracted data on clinically relevant endpoints, i.e. overall survival (OS) or progression-free survival (PFS), in accordance with the PRISMA statements. RESULTS The search strategy yielded 6389 unique articles, of which 150 met the inclusion criteria. 37 studies found an association between survival outcomes and pre-operative markers including complete blood count (erythrocytes and leukocytes with differentiation characteristics), inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), coagulability markers (prothrombin time, activated partial thromboplastin time and D-dimer), albumin, lactate dehydrogenase and glucose. Furthermore, 10 studies reported a correlation between changes in platelets, erythrocytes and leukocytes during course of disease and treatment and OS. Finally, serum and plasma levels of markers including various proteins, microRNAs and microvesicles were associated with PFS and OS. CONCLUSION The results of this study suggest that routine and specialized blood tests provide additive information on OS and PFS in glioblastoma. These promising findings highlight the need for further investigation of blood testing for biomarker evaluation.

Prostate Cancer in 2021: Novelties in Prognostic and Therapeutic Biomarker Evaluation

The 2021 novelties in prognostic and therapeutic tissue markers in patients with prostate cancer (PCa) can be subdivided into two major groups. The first group is related to prognostic markers based on morphological and immunohistochemical evaluations. The novelties in this group can then be subdivided into two subgroups, one involving morphologic evaluation only, i.e., PCa grading, and the other involving both morphologic and immunohistochemical evaluations, i.e., aggressive variant PCa (AVPCa). Grading concerns androgen-dependent PCa, while AVPCa represents a late phase in its natural history, when it becomes androgen-independent. The novelties of the other major group are related to molecular markers predicting significant disease or response to therapy. This group mainly includes novelties in the molecular evaluation of PCa in tissue material and liquid biopsies.

Future of biomarker evaluation in the realm of artificial intelligence algorithms: application in improved therapeutic stratification of patients with breast and prostate cancer

Clinical workflows in oncology depend on predictive and prognostic biomarkers. However, the growing number of complex biomarkers contributes to costly and delayed decision-making in routine oncology care and treatment. As cancer is expected to rank as the leading cause of death and the single most important barrier to increasing life expectancy in the 21st century, there is a major emphasis on precision medicine, particularly individualisation of treatment through better prediction of patient outcome. Over the past few years, both surgical and pathology specialties have suffered cutbacks and a low uptake of pathology specialists means a solution is required to enable high-throughput screening and personalised treatment in this area to alleviate bottlenecks. Digital imaging in pathology has undergone an exponential period of growth. Deep-learning (DL) platforms for hematoxylin and eosin (H&E) image analysis, with preliminary artificial intelligence (AI)-based grading capabilities of specimens, can evaluate image characteristics which may not be visually apparent to a pathologist and offer new possibilities for better modelling of disease appearance and possibly improve the prediction of disease stage and patient outcome. Although digital pathology and AI are still emerging areas, they are the critical components for advancing personalised medicine. Integration of transcriptomic analysis, clinical information and AI-based image analysis is yet an uncultivated field by which healthcare professionals can make improved treatment decisions in cancer. This short review describes the potential application of integrative AI in offering better detection, quantification, classification, prognosis and prediction of breast and prostate cancer and also highlights the utilisation of machine learning systems in biomarker evaluation.

Biomarker evaluation in radically resectable locally advanced gastric cancer treated with neoadjuvant chemotherapy: an evidence reappraisal

Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced resectable gastric cancer but, despite important progresses, relapse-related death remains a major challenge. Therefore, it appears crucial to understand which patients will benefit from peri-operative treatment. Biomarkers such as human epidermal growth factor receptor-2 (HER2), microsatellite instability (MSI), and Epstein-Barr Virus (EBV) have been widely studied; however, they do not yet guide the choice of perioperative treatment in clinical practice. We performed a narrative review, including 23 studies, addressing the value of tissue- or blood-based biomarkers in the neoadjuvant setting. Ten studies (43.5%) were prospective, and more than half were conducted in East-Asia. Biomarkers were evaluated only post-NAC (on surgical samples or blood) in seven studies (30.4%), only pre-NAC (on endoscopic specimens or blood) in 10 studies (43.5%), and both pre- and post-NAC (26.1%) in six studies. Among the high variety of investigated biomarkers, some of these including MSI-H or enzymatic profile (as TS, UGT1A1, MTHFR, ERCC or XRCC) showed promising results and deserve to be assessed in methodologically sound clinical trials. The identification of molecular biomarkers in patients treated with NAC for locally advanced resectable gastric or EGJ cancer remains crucial.