1.Prognostic role of genetic biomarkers in clinical progression of prostate cancer.
Maria Jesus ALVAREZ-CUBERO ; Luis Javier MARTINEZ-GONZALEZ ; Maria SAIZ ; Pedro CARMONA-SAEZ ; Juan Carlos ALVAREZ ; Manrique PASCUAL-GELER ; Jose Antonio LORENTE ; Jose Manuel COZAR
Experimental & Molecular Medicine 2015;47(8):e176-
The aim of this study was to analyze the use of 12 single-nucleotide polymorphisms in genes ELAC2, RNASEL and MSR1 as biomarkers for prostate cancer (PCa) detection and progression, as well as perform a genetic classification of high-risk patients. A cohort of 451 men (235 patients and 216 controls) was studied. We calculated means of regression analysis using clinical values (stage, prostate-specific antigen, Gleason score and progression) in patients and controls at the basal stage and after a follow-up of 72 months. Significantly different allele frequencies between patients and controls were observed for rs1904577 and rs918 (MSR1 gene) and for rs17552022 and rs5030739 (ELAC2). We found evidence of increased risk for PCa in rs486907 and rs2127565 in variants AA and CC, respectively. In addition, rs627928 (TT-GT), rs486907 (AG) and rs3747531 (CG-CC) were associated with low tumor aggressiveness. Some had a weak linkage, such as rs1904577 and rs2127565, rs4792311 and rs17552022, and rs1904577 and rs918. Our study provides the proof-of-principle that some of the genetic variants (such as rs486907, rs627928 and rs2127565) in genes RNASEL, MSR1 and ELAC2 can be used as predictors of aggressiveness and progression of PCa. In the future, clinical use of these biomarkers, in combination with current ones, could potentially reduce the rate of unnecessary biopsies and specific treatments.
Aged
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Aged, 80 and over
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Cohort Studies
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Disease Progression
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Endoribonucleases/*genetics
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Gene Frequency
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Genetic Markers/genetics
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Genetic Predisposition to Disease
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Humans
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Male
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Middle Aged
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Neoplasm Proteins/*genetics
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*Polymorphism, Single Nucleotide
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Prognosis
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Prostate/metabolism/*pathology
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Prostatic Neoplasms/*diagnosis/*genetics
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Scavenger Receptors, Class A/*genetics
2.Post-mortem assessment of vimentin expression as a biomarker for renal tubular regeneration following acute kidney injury
Juan Carlos Alvarez MORENO ; Hisham F. BAHMAD ; Christopher A. FEBRES-ALDANA ; Andrés PIRELA ; Andres AZUERO ; Ali SALAMI ; Robert POPPITI
Journal of Pathology and Translational Medicine 2021;55(6):369-379
Background:
Acute kidney injury (AKI) is a common cause of morbidity and mortality. It mainly targets the renal tubular epithelium with pathological changes, referred to as acute tubular injury. The latter is followed by a regenerative response that is difficult to visualize on routine hematoxylin and eosin (H&E) stains. In this study, we examined the regenerative capacity of renal tubules by correlating vimentin (VIM) immunohistochemical (IHC) expression and pathological findings of AKI and renal tubular regeneration (RTR) on H&E.
Methods:
We reviewed 23 autopsies performed in the clinical setting of AKI and RTR. VIM expression was scored in the renal cortical tubular epithelium using a statistical cutoff ≥ 3% for high expression and < 3% for low expression.
Results:
Of the 23 kidney tissues examined, seven (30.4%) had low VIM expression, and 16 (69.6%) had high VIM expression. Kidney tissues with evidence of AKI and RTR had significantly higher VIM expression. Renal peritubular microenvironment features showing regenerative changes on H&E were associated with high VIM expression. In the univariate model, kidney tissues with RTR were 18-fold more likely to have high VIM expression.
Conclusions
In conclusion, our findings suggest that VIM could serve as an IHC marker for RTR following AKI. However, correlation with H&E findings remains critical to excluding chronic tubular damage. Collectively, our preliminary results pave the way for future studies including a larger sample size to validate the use of VIM as a reliable biomarker for RTR.