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

Lucia Borszéková Borszéková Pulzová,Michal Mego,Mangesh R Bhide,Peter Bujdák,Eduard Goffa,Božena Smolková,Jan Roška,Miroslav Chovanec,Michal Kalman,Ján Kliment,Lukáš Plank,Ľudovít Kulcsár,Pavol Slávik,Katarína Lešková,Dana Jurkovičová

doi:10.3390/cancers13215573

Abstract

Simple SummaryFor 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.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.

Highlights

Clinical stage I (CS I) seminoma patients have a very good prognosis, with an overall survival (OS) rate of 98%
Six clinical stage I (CS I) seminoma patient samples were used in the proteomic analysis aimed at revealing factors that are differentially expressed upon
64 proteins were found to be differentially expressed in Rete testis invasion (RTI)-positive vs. -negative CS I seminoma, where expression changes higher than 20% were taken as a cut-off criterion, with 44 and 20 proteins being up- and down-regulated, respectively (Table S2)

Summary

Introduction

Clinical stage I (CS I) seminoma patients have a very good prognosis, with an overall survival (OS) rate of 98% These patients are characterized by disease confined to the testicle, postorchiectomy normalized tumour markers, negative imaging of the chest, abdomen, and pelvis, and a normal physical examination. Adjuvant therapy managed by chemotherapy or radiation therapy represents an option to reduce the risk of relapse in CS I seminoma patients. Both irradiation of the equilateral retroperitoneal lymphatic tissue and intravenous administration of carboplatin (1 or 2 cycles) lower relapse risk to less than 5% [3,4,5]. Consistent prognostic factors for the prediction of relapse, and for guiding the management of these patients after orchiectomy—

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