On multivariate analysis, PNI was associated with local disease recurrence (P=.02) while LVI was associated with progression to metastatic disease (P=.002) and increased overall mortality (P=.02).
The extracellular serine protease inhibitor serpinE2, also named protease nexin-1 (PN-1), contributes to enhanced metastasis of cancer cells mainly by remodeling the tumor matrix.
Higher expression of SerpinE2 was shown in osteosarcoma tissues, particularly in tissue from patients with metastasis and a tumor-node-metastasis stage II‑III.
The in silico approach was complemented by mechanistic studies on two mammary cancer cell lines, the PN-1-negative 168FARN cells and the PN-1-positive 4T1 cells, both of which form primary mammary tumors, but only 4T1 tumors are able to metastasize to the lungs.
One of the genes most strongly overrepresented in the highly metastatic subclone S2-007 as compared with the rarely metastatic subclone S2-028 was the serine proteinase inhibitor SERPINE2 (protease nexin I), suggesting that this protein may play an important part in the process of metastasis.