Matrix metalloproteinase-13 expression is associated with bone marrow microinvolvement and prognosis in non-small cell lung cancer.
Our previous study demonstrated that bone marrow microinvolvement (BMM) is an epiphenomenon of tumor progression rather than a prognostic factor in non-small cell lung cancer. We hypothesize that an increase in mesenchymal transition power in epithelial tumor cells by up-regulation of the matrix metalloproteinases (MMPs) may contribute to the existence of BMM and poorer prognosis. Hereby we conducted a prospective study of BMM and MMPs expression in a cohort of 57 non-small cell lung cancer patients. Bone aspirates were examined by immunohistochemical stains. Expressions of MMPs were checked by Human MMP primer set kit (Maxim Biotech, USA). Correlations between the MMPs expression and BMM, nodal metastasis, and prognosis were examined. Cox model analysis was used to identify independent prognostic factors. Though positive BMM was identified in 38 (66.7%) of the patients, none of the clinicopathological factors, including sex, age, cell types, tumor differentiation, nodal metastasis and TNM status of the tumor, was related to BMM by the tumor cells. Up-regulation was observed in a broad spectrum of MMPs with the exception of MMP-3. However, only MMP-13 expression correlated with the existence of BMM (p=0.006). Univariate analysis revealed MMP-3, MMP-7 and MMP-13 as negative prognostic factors. Cox model analysis revealed T-status, cell differentiation, and MMP-13 expression of the tumor as independent prognostic factors. The overall 5-year survival rate of the patients was 36.8%. The existence of BMM itself did not influence the prognosis (p=0.109), however, patients with positive MMP-13 expression (N=34) had a poorer 5-year survival rate of 26.5% (p=0.025). In summary, non-small cell lung cancer cells with MMP-13 expression, despite of BMM status, tend to shed and aggregate in the bone marrow, which is subsequently reflected in a poorer survival rate.
Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, and School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. cliff@vghtc.gov.tw
Chung-Ping
CP
Hsu
Gwan-Han
GH
Shen
Jiunn-Liang
JL
Ko
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D019046:Bone Marrow Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation; D017364:Collagenases / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011446:Prospective Studies; D012737:Sex Factors; D015996:Survival Rate; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13