Osteopontin-expressing macrophages in non-small cell lung cancer predict survival

Tumor-associated macrophages (TAMs) are a major component of leukocyte infiltration in the tumor microenvironment. Osteopontin is related to tumor metastasis and proliferation. Osteopontin is expressed not only by tumor cells but also by TAMs. The purpose of the current study was to assess the prognostic significance of osteopontin expressed by TAMs (TOPN) in patients with non-small cell lung cancer.

Tissue microarray was used to detect the expression of TOPN, TAMs, and microvascular density in 159 patients with non-small cell lung cancer undergoing complete pulmonary resection in our hospital between 2003 and 2006. The correlations between TOPN, TAMs, and clinicopathologic data were analyzed with χ(2) tests. Quantitation of TAMs or TOPN and microvascular density analyses was performed using Bonferroni correction and the Student's t test. The prognostic value of TOPN was evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis.

In the recurrence and metastasis group, microvascular density was higher than that in the control group (14.4 ± 1.06 versus 8.9 ± 1.02; p = 0.0002). In the TOPN-positive group, microvascular density was increased compared with that in the TOPN-negative group (14.3 ± 1.37 versus 10.7 ± 0.91; p = 0.0273). Osteopontin expressed by TAMs was an independent predictor for overall survival (p = 0.017) and disease-free survival (p < 0.001), especially for stage I non-small cell lung cancer. The 6-year overall and disease-free survival rates in TOPN-positive patients were 22.64% and 16.98%, respectively, which were significantly lower than those of TOPN-negative patients (50.00% and 39.62%, respectively).

Osteopontin expressed by TAMs is a valuable independent predictor of tumor recurrence and survival in patients with non-small cell lung cancer.