Screening for the Key Proteins Associated with Rete Testis Invasion in Clinical Stage I Seminoma via Label-Free Quantitative Mass Spectrometry

SIMPLE SUMMARY: For clinical stage I (CS I) seminoma patients, management through the risk-adapted strategy with adjuvant carboplatin-based chemotherapy in the presence of risk factors and surveillance in the absence of these factors is the preferred option. In such management, rete testis invasion (RTI) represents a prognostic factor, as its absence, together with a tumour diameter ≤4 cm is associated with a very low relapse risk. To be able to routinely manage CS I seminoma patients through a risk-adapted strategy, reliable biomarkers stratifying the risk of relapse for CS I seminoma patients are urgently required. However, no such biomarker has yet entered routine use in clinical decision-making or clinical guidelines. The lack of consistent prognostic biomarkers for CS I seminoma patients prompted us to compare the proteomic profiles of RTI-positive and -negative CS I seminomas to reveal the molecular mechanism(s) and, in particular, the corresponding biomarkers of RTI invasion. ABSTRACT: Rete testis invasion (RTI) is an unfavourable prognostic factor for the risk of relapse in clinical stage I (CS I) seminoma patients. Notably, no evidence of difference in the proteome of RTI-positive vs. -negative CS I seminomas has been reported yet. Here, a quantitative proteomic approach was used to investigate RTI-associated proteins. 64 proteins were differentially expressed in RTI-positive compared to -negative CS I seminomas. Of them, 14-3-3γ, ezrin, filamin A, Parkinsonism-associated deglycase 7 (PARK7), vimentin and vinculin, were validated in CS I seminoma patient cohort. As shown by multivariate analysis controlling for clinical confounders, PARK7 and filamin A expression lowered the risk of RTI, while 14-3-3γ expression increased it. Therefore, we suggest that in real clinical biopsy specimens, the expression level of these proteins may reflect prognosis in CS I seminoma patients.