Abstract
Many studies show that CXC chemokine ligand 14 (CXCL14) is highly expressed in tumor-associated stromal cells, promoting tumor cell growth, and invasion. Because of its unclear receptors, CXCL14-initiated intracellular signal cascades remain largely unknown. However, CXCL14 can regulate nitric oxide synthase 1 (NOS1) as its intracellular molecular target. In this paper, we investigated the expression of CXCL14 and NOS1 in specimens from patients with stage I-IIIA nonsmall cell lung cancer (NSCLC) after curative resection, and evaluated the prognostic significance of this gene expression in stromal fibroblasts and cancer cells.Immunohistochemistry was used to detect the expression of CXCL14 and NOS1 in 106 formalin fixed, paraffin-embedded specimens from patients with stage I-IIIA NSCLC. The chi-square test was performed to examine the correlation of CXCL14 and NOS1 expression level with clinicopathological features. The effects of the expression of CXCL14 or NOS1 on progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier and Cox hazard proportional model.The percentages of high CXCL14 expression in stromal fibroblasts and that in cancer cells were 46.2% (49/106) and 23.6% (25/106), respectively. The positive expression rates of NOS1 in cancer cells were 42.5% (45/106). The result indicated that there was a significant positive correlation between CXCL14 expression level in stromal fibroblasts and that in cancer cells (χ = 4.158, P = .041). In addition, the expression of CXCL14 in stromal fibroblasts was significantly correlated with NOS1 expression in cancer cells (χ = 16.156, P < .001). The 5-year PFS rates with low and high CXCL14 expression in stromal fibroblasts were 66.7% and 14.3% (χ = 44.008, P < .001), respectively, and the 5-year OS rates with those were 87.1% and 43.5% (χ = 21.531, P < .001), respectively. The 5-year PFS rates with negative and positive expression of NOS1 in cancer cells were 62.3% and 15.6% (χ = 33.756, P < .001), respectively, and the 5-year OS rates with those were 86.4% and 40.1% (χ = 24.430, P < 0.01), respectively.Both the high expression of CXCL14 in stromal fibroblasts and the positive expression of NOS1 in cancer cells are independent negative predictors of PFS and OS in patients with stage I-IIIA NSCLC after curative resection.