Serum response factor, a novel early diagnostic biomarker of acute kidney injury.

OBJECTIVE: Studies have shown that serum response factor (SRF) is increased in chronic kidney injury, such as diabetic nephropathy, hyperuricemic nephropathy and renal cell carcinoma. The objective is to explore the early diagnostic value of SRF in acute kidney injury (AKI). METHODS: AKI-related microarray data were analyzed, and the expression and location of SRF were investigated in the early phase of AKI. RESULTS: Bioinformatics results demonstrated that SRF was dramatically elevated 2-4 h after ischemia/reperfusion (I/R) in mouse renal tissue. In I/R rats, SRF was mostly expressed and located in renal tubular epithelial cells (TECs). SRF started to increase at 1 h, peaked at 3-9 h and started to decrease at 12 h after I/R. The areas under the ROC curve of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF and serum creatinine (Scr) were 87.9%, 83.0%, 81.3%, 78.8%, 68.8%, respectively. CONCLUSION: SRF is remarkably upregulated in early (before 24 h) AKI and can replace Scr as a potential new early diagnostic biomarker of AKI.

Clinical Significance and Potential Regulatory Mechanisms of Serum Response Factor in 1118 Cases of Thyroid Cancer Based on Gene Chip and RNA-Sequencing Data.

BACKGROUND Thyroid cancer (TC) is one of the most prevalent endocrine malignancies and there may be many unclarified molecular events and gene types involved in TC. The objective of this study was to assess the clinical implications and potential mechanisms of serum response factor (SRF) in TC. MATERIAL AND METHODS RNA-sequencing and gene chip data with TC expression were collected from The Cancer Genome Atlas/Genotype-Tissue Expression, Gene Expression Omnibus, ArrayExpress, Sequence Read Archive, and Oncomine. SRF expression of all TC and adjacent non-cancerous tissue were calculated using the t test, STATA, and Meta-DiSc. The related pathways of the potential SRF target genes and target miRNAs were explored. Dual-luciferase reporter assay was performed to validate the association between SRF and its putative miRNA. RESULTS One RNA-sequencing and 15 gene chips were collected, and the pooled standardized mean difference of SRF was -1.00. Furthermore, the area under the curve of sROC of SRF in TC was 0.8251, indicating a dramatic decreased expression of SRF in TC tissues based on 1118 cases. The intersection of differentially expressed genes in TC, SRF co-expressed genes, and SRF potential target genes achieved from Cistrome Cancer led to 169 overlapped genes. miR-330-5p was predicted to target SRF, which was further confirmed by dual-luciferase reporter assay. CONCLUSIONS The reduction of SRF appears to play a crucial role in the origin of TC. These properties are accomplished by the target genes of SRF, as a transcription factor, or by the axes with the associated miRNAs.

Role of serum response factor expression in prostate cancer biochemical recurrence.

BACKGROUND: Up to a third of prostate cancer patients fail curative treatment strategies such as surgery and radiation therapy in the form of biochemical recurrence (BCR) which can be predictive of poor outcome. Recent clinical trials have shown that men experiencing BCR might benefit from earlier intervention post-radical prostatectomy (RP). Therefore, there is an urgent need to identify earlier prognostic biomarkers which will guide clinicians in making accurate diagnosis and timely decisions on the next appropriate treatment. The objective of this study was to evaluate Serum Response Factor (SRF) protein expression following RP and to investigate its association with BCR. MATERIALS AND METHODS: SRF nuclear expression was evaluated by immunohistochemistry (IHC) in TMAs across three international radical prostatectomy cohorts for a total of 615 patients. Log-rank test and Kaplan-Meier analyses were used for BCR comparisons. Stepwise backwards elimination proportional hazard regression analysis was used to explore the significance of SRF in predicting BCR in the context of other clinical pathological variables. Area under the curve (AUC) values were generated by simulating repeated random sub-samples. RESULTS: Analysis of the immunohistochemical staining of benign versus cancer cores showed higher expression of nuclear SRF protein expression in cancer cores compared with benign for all the three TMAs analysed (P < 0.001, n = 615). Kaplan-Meier curves of the three TMAs combined showed that patients with higher SRF nuclear expression had a shorter time to BCR compared with patients with lower SRF expression (P < 0.001, n = 215). Together with pathological T stage T3, SRF was identified as a predictor of BCR using stepwise backwards elimination proportional hazard regression analysis (P = 0.0521). Moreover ROC curves and AUC values showed that SRF was better than T stage in predicting BCR at year 3 and 5 following radical prostatectomy, the combination of SRF and T stage had a higher AUC value than the two taken separately. CONCLUSIONS: SRF assessment by IHC following RP could be useful in guiding clinicians to better identify patients for appropriate follow-up and timely treatment.

The imbalance of vascular molecules in Alzheimer's disease.

The vascular system plays an integral role during Alzheimer's disease (AD). Both systemic circulatory changes and alterations directly within the brain vasculature have been suggested to contribute to both the onset and progression of neurological conditions such as AD. It is now well established that vascular risk factors including hypertension, diabetes, obesity, atherosclerosis, metabolic syndrome, and stroke significantly increase one's risk of later developing AD. Research within the last decade has begun to identify specific vascular molecules associated with such risk factors as well as elucidate the biological role they may play in the pathological processes linked to AD. This review aims to provide an overview of some of the key molecules within vascular cells and circulating in blood that have been identified to be altered in AD pathogenesis. In particular, the vascular-specific transcription factors MEOX2, MYOCD, and SRF, genetic risk factor APOE4, transport proteins LRP1 and RAGE, and circulating molecules such as sLRP1, homocysteine, and albumin are discussed. I aim to clarify how these identified vascular molecules may help to predict, explain, and influence the incidence AD. A strong emphasis is placed on the concept that these molecules play overlapping roles in cardiovascular disease progression, neurovascular dysfunction, and amyloid-ß pathology. The studies reviewed here have identified vascular-based molecular targets in AD and thus provide new therapeutic avenues for the treatment of this devastating disease.