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. 2022 Mar 17;10(3):698.
doi: 10.3390/biomedicines10030698.

Elevated Pre-Treatment Serum MMP-7 Levels Are Associated with the Presence of Metastasis and Poor Survival in Upper Tract Urothelial Carcinoma

Petra Terézia Kovács  1 , Tamás Mayer  1 , Anita Csizmarik  1 , Melinda Váradi  1 , Csilla Oláh  2 , Ádám Széles  1 , Stephan Tschirdewahn  2 , Ulrich Krafft  2 , Boris Hadaschik  2 , Péter Nyirády  1 , Péter Riesz  1 , Tibor Szarvas  1   2
Affiliations

Elevated Pre-Treatment Serum MMP-7 Levels Are Associated with the Presence of Metastasis and Poor Survival in Upper Tract Urothelial Carcinoma

Petra Terézia Kovács et al. Biomedicines. .

Abstract

Upper tract urothelial carcinoma (UTUC) is a rare cancer with a barely predictable clinical behaviour. Serum MMP-7 is a validated prognostic marker in urothelial bladder cancer, a tumour entity with large clinical, histological, and molecular similarity to UTUC. The serum MMP-7 levels have not yet been investigated in UTUC. In the present study, we determined MMP-7 concentrations in an overall number of 103 serum samples from 57 UTUC patients who underwent surgical or systemic (platinum or immune checkpoint inhibitor) therapy by using the ELISA method. In addition to pre-treatment samples, the serum samples collected at predefined time points after or during therapy were also investigated. Serum MMP-7 concentrations were correlated with clinicopathological and follow-up data. Our results revealed significantly, two-fold elevated pre-treatment serum MMP-7 levels in metastatic cases of UTUC in both the radical surgery- and the chemotherapy-treated cohorts (p = 0.045 and p = 0.040, respectively). In addition, high serum MMP-7 levels significantly decreased after radical surgery, and high pre-treatment MMP-7 concentrations were associated with shorter survival both in the surgery- and chemotherapy-treated cohorts (p = 0.029 and p = 0.001, respectively). Our results revealed pre-treatment serum MMP-7 as a prognostic marker for UTUC, which may help to improve preoperative risk-stratification and thereby improve therapeutic decision-making.

Keywords: MMP-7; UTUC; biomarker; chemotherapy; immune checkpoint inhibitor therapy; matrix metalloproteinase; prognosis; radical nephroureterectomy; upper urinary tract cancer.

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Conflict of interest statement

Boris Hadaschik reported personal fees and non-financial support from AstraZeneca, Amgen, Bayer, BMS, and Janssen; personal fees from ABX, Lightpoint medical Inc, and Pfizer; and grant funding from German Research Foundation, BMS, and Novartis, all outside the submitted work. Tibor Szarvas received fees from BRAHMS and Janssen outside of the present study. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Association of preoperative serum MMP-7 concentration and clinicopathological parameters in the RNU cohort (* significant difference).
Figure 2
Figure 2
Kaplan–Meier OS analyses with log-rank tests (A) for the RNU cohort with a median value, (B) for the RNU cohort with an ROC cut-off, (C) for CTX cohort with a median value, and (D) for the CTX cohort with an ROC cut-off (blue line—low MMP-7 cc., green line—high MMP-7 cc.; cut-off values are shown on each line).
Figure 3
Figure 3
(A) Changes of MMP-7 concentrations in the RNU cohort (preop. and postop. values). (B) Changes of MMP-7 concentrations in the CTX cohort (at chemotherapy baseline and on the first day of cycle 2). (C) Changes of MMP-7 concentrations in the ICI cohort (pre-treatment and on-treatment values). (D) Changes of MMP-7 concentrations in the RNU, CTX, and ICI cohorts (* significant difference); RNU—radical nephroureterectomy; CTX—chemotherapy; ICI—immune checkpoint inhibitor therapy.
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