Lipocalin-2 as a biomarker for diabetic nephropathy

Diabetes is a major global public health issue.The prevalence of type 1 diabetes is comparatively static,as hereditary and genetic causes are involved,while type 2 diabetes(T2D)prevalence is increasing day by day.T2D is associated with chronic complications,including diabetic neuropathy(DN),nephropathy,retinopathy,and other complications like diabetic foot.DN is the main complication of both types of diabetes.DN can be diagnosed by routine laboratory tests,microalbuminuria>300 mg/24 h,and a gradual decrease in glomerular filtration rate.As the appearance of microalbuminuria is a late manifestation,an early marker for renal damage is needed.Lipocalin-2,also known as neutrophil gelatinaseassociated lipocalin(NGAL),is a small protein purified from neutrophil granules and a good marker for kidney disease.NGAL is a transporter protein responsible for many physiological processes,such as inflammation,generation of the immune response,and metabolic homeostasis.NGAL has been reported to depict the early changes in renal damage when urine microalbumin is still undetecable.Therefore,elucidating the role of NGAL in detecting DN and understanding its mechanism can help establish it as a potential early marker for DN.

Matricellular proteins as possible biomarkers for early brain injury after aneurysmal subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury（EBI）.In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,poor initial clinical grades,and some radiographic findings are used,but these markers are somewhat subjective.Thus,it is imperative to find biomarkers of EBI that have beneficial prognostic and therapeutic implications.In our opinion,an ideal biomarker is a molecule that is implicated in the pathogenesis of both EBI and subsequently developing delayed cerebral ischemia（DCI）,being a therapeutic target,and can be measured easily in the peripheral blood in an acute stage.A good candidate of such a biomarker is a matricellular protein,which is a secreted,inducible and multifunctional extracellular matrix protein.There are many kinds of matricellular proteins reported,but only tenascin-C,osteopontin,galectin-3 and periostin are reported relevant to EBI and DCI.Reliable biomarkers of EBI may stratify aneurysmal subarachnoid hemorrhage patients into categories of risk to develop DCI,and allow objective monitoring of the response to treatment for EBI and earlier diagnosis of DCI.This review emphasizes that further investigation of matricellular proteins as an avenue for biomarker discovery is warranted.

Current early diagnostic biomarkers of prostate cancer

Prostate cancer （PCa） has become to have the highest incidence and the second mortality rate in western countries, affecting men＇s health to a large extent. Although prostate-specific antigen （PSA） was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.

Oral microbiome and risk of malignant esophageal lesions in a high-risk area of China:A nested case-control study

Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods:We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China.The oral microbiome was evaluated with 16 S ribosomal RNA(rRNA)gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above(SDA)and 168 matched healthy controls.DESeq analysis was performed to identify taxa of differential abundance.Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.Results:A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls(all P<0.05&false discovery rate-adjusted Q<0.10).A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve(AUC)of 0.89(95%CI,0.84-0.93).Cross-validation and sensitivity analysis,excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls,or restriction to screenendoscopic-detected or clinically diagnosed case-control triads,or using only bacterial data measured at the baseline,yielded AUCs>0.84.Conclusions:The oral microbiome may play an etiological and predictive role in esophageal cancer,and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.

Application of serum surface-enhanced laser desorption/ionization proteomic patterns in distinguishing lung cancer patients from healthy people

Screening and early diagnosis of lung cancer relies mainly on chest X-ray, low-dose computed tomography, bronchoscopy, sputum cytology, and measurement of tumor markers such as carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), and neuron-specific enolase (NSE). However, all these methods lack adequate sensitivity and/or specificity. 1-3 Better methods are therefore urgently needed in screening and early diagnosis of lung cancer, and proteomic fingerprinting represents a promising approach. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), an innovative proteomic technology, has overcome many of the limitations of two-dimensional electrophoresis (2D) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). 4,5 Recently, this technology has been successfully used to distinguish pancreatic, ovarian and prostate cancer patients from healthy control subjects. 5-7 The aim of the current study was to investigate the application of serum SELDI protein profiling in distinguishing lung cancer patients from healthy persons.