Proteomic Patterns and Transcriptional Evaluation Reveals Prognostic Potential of Novel Serum Biomarkers in Progression of Prostate Cancer

Abstract

Objective: Aging population, stressfully transforming lifestyle and perturbed urological physiology are contributing to the recent incidence of anxious rise in prostate cancer (PCa) across the globe, including India. Despite of advancing knowledge and decades of applied urological research, the existing insights are insufficient to curb the menace. This very situation intrigued us to investigate and identify the differential and clinically relevant prognostic serum based biomarkers in induced animal model of PCa with an intention to contribute an insight in early and accurate detection and additive avenues for effective clinical case management. Methods: We employed 2-DE and MALDI-TOF-MS techniques followed by tissue diagnosis for pathophysiological characterization and disease differentiation that were assessed by histopathology and to corroborate the sustainable evidences of proteomics observations and to ascertain the functional association and regulation of corresponding genes; transcriptional genomics were performed using qRT-PCR. Results and Conclusion: We distinctly observed SRCIN1, DCAF6, PTP4A2 and MRPL15; novel and under investigated serum markers in protein profiling and time dependent differentially expressed patterns of respective genes in Wistar rat PCa tissues. We found significantly upregulated expression of MRPL15 and quite early pronounced shift (4.9 fold), suggesting specificity and efficiently early tumour inducer candidate marker; whereas DCAF6, though showed overall upregulation, but pronounced and noticeable shift (7.8 fold) was observed quite late; suggesting time dependent sensitivity as marker’s characterization of late tumour inducer candidate. Further, SRCIN1 were down regulated irrespective of time course, whereas PTP4A2 were also down regulated but quite late and marginally showed non-significant upregulation (<0.5 fold); suggesting specificity of SRCIN1 and PTP4A2, as tumour suppressor marker. However, PTP4A2 may have dichotomic potential as quite late phase tumour inducer marker candidate as well. In conclusion, these proteins may therefore possess a potential candidature in improving PCa diagnosis during its early stage. Further functional and clinical validation studies of these cancer-associated proteins are necessary to elucidate their precise role in the process of prostate carcinogenesis.