Lung and blood perioperative metalloproteinases in patients undergoing oncologic lung surgery: Prognostic implications

Abstract

Background: Metalloproteinases (MMPs) have been reported to be related to oncologic outcomes. The main goal of the study was to study the relationship between these proteins and the long-term prognosis of patients undergoing oncologic lung resection surgery.

Methods: This was a substudy of the phase IV randomized control trial (NCT02168751). We analyzed MMP-2, -3, -7, and -9 in blood samples and bronchoalveolar lavage (LBA) and the relationship between MMPs and long postoperative outcomes (survival and disease-free time of oncologic recurrence).

Results: Survival was longer in patients who had lower MMP-2 levels than those with higher MMP-2 in blood samples taken 6 h after surgery (6.8 vs. 5.22 years; p = 0.012) and MMP-3 (6.82 vs. 5.35 years; p = 0.03). In contrast, survival was longer when MMP-3 levels were higher in LBA from oncologic lung patients than those with lower MMP-3 (7.96 vs. 6.02 years; p = 0.005). Recurrence-free time was longer in patients who had lower MMP-3 levels in blood samples versus higher (5.97 vs. 4.23 years; p = 0.034) as well as lower MMP-7 (5.96 vs. 4.5 years; p = 0.041) or lower MMP-9 in LBA samples (6.21 vs. 4.18 years; p = 0.012).

Conclusion: MMPs were monitored during the perioperative period of oncologic lung resection surgery. These biomarkers were associated with mortality and recurrence-free time. The role of the different MMPs analyzed during the study do not have the same prognostic implications after this kind of surgery.

Keywords: liquid biopsy; metalloproteinases; oncologic disease-free time; oncologic lung surgery; survival.

FIGURE 1

Perioperative course MMP. Footnote. MMP, metalloproteinases; OLV30mins: 30 min after starting one‐lung ventilation; OLV end: At the end of One‐lung ventilation; PO, postoperative; DL, dependent lung; non‐DL, nondependent lung.

FIGURE 2

Kaplan–Meier survival and oncologic recurrence curves for high MMP 2,3,7, and 9 (interquartile ≥ 75) and low expression (interquartile < 75) in blood samples. Footnote. (a) Left column shows survival Kaplan Meier curves in patients with high versus low MMPs measured in blood samples 6 h after the end of surgery. (b) The right column shows recurrence‐free time oncologic illness Kaplan Meier curves in patients with high versus low MMPs measured in blood samples 6 h after the end of surgery. Black lines correspond to high values of MMP 2,3,7, and 9 (interquartile ≥ 75) and the gray lines correspond to low expression (interquartile < 75) of those MMPs. To compare patients with low or high MMPs we used a log rank test.

FIGURE 3

Kaplan–Meier survival and oncologic recurrence curves for high metalloproteinases (MMP) 2,3,7, and 9 (interquartile ≥ 75) and low expression (interquartile < 75) in bronchoalveolar lavage samples. Footnote. (a) The left column shows Kaplan Meier survival curves in patients with high versus low MMPs measured in bronchoalveolar lavage before the start of one‐lung ventilation. (b) The right column shows oncologic recurrence‐free time Kaplan Meier curves in patients with high versus low MMPs measured in bronchoalveolar lavage before the start of one‐lung ventilation. Black lines correspond to high values of MMP 2,3,7, and 9 (interquartile ≥ 75) and the gray lines correspond to low expression (interquartile < 75) of those MMPs. To compare patients with low or high MMPs we used log rank test.