The prognostic value of serum C-reactive protein-bound serum amyloid A in early-stage lung cancer.

BACKGROUND: Elevated levels of serum C-reactive protein (CRP) have been reported to have prognostic significance in lung cancer patients. This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value. METHODS: CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis. CRP-bound serum amyloid A (CRP-SAA) was evaluated by co-immunoprecipitation (IP). Serum samples from two independent cohorts with lung cancer (retrospective cohort, 242 patients; prospective cohort, 222 patients) and healthy controls (159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay. RESULTS: CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis. CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media. The level of CRP-SAA was significantly higher in patients than in healthy controls (0.37 ± 0.58 vs. 0.03 ± 0.04, P < 0.001). Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer. The elevation of CRP-SAA was associated with lower survival rates for both the retrospective (hazard ration [HR] = 2.181, 95% confidence interval [CI] = 1.641-2.897, P < 0.001) and the prospective cohorts (HR = 2.744, 95% CI = 1.810-4.161, P < 0.001). Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer. Remarkably, in stages I-II patients, only CRP-SAA, not total SAA or CRP, showed significant association with overall survival in two cohorts. Moreover, univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients. CONCLUSION: CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP, especially in early-stage patients.

[Experimental study of NK4 gene targeted therapy mediated by human telomerase reverse transcriptase promoter for colon cancer].

OBJECTIVE: To investigate anti-tumor effect of the recombined adenovirus encoding NK4 gene regulated by human telomerase reverse transcriptase (HTERT) promoter (Ad HTERTp-NK4) on human colon cancer. METHODS: Colon cell line HCT116 was infected with Ad HTERTp-NK4. NK4 expression was determined by RT-PCR and Western blot. The cell-growth inhibition rate and the invasive capacity of cells were evaluated by MTT method and reconstituted basement membrane invasion assay. The model of subcutaneous tumor was generated by injection of HCT116 cells into the dorsum of nude mice. Ad HTERTp-NK4 was injected around the tumor tissues, and tumor growth was observed. RESULTS: NK4 gene was highly expressed in infected HCT116 cells. The cell growth inhibition rate and the invasive inhibition rate in Ad HTERTp-NK4 cells were 47.14% and 40.63% respectively, which were significantly higher than those in the control cells (2.75% and 2.31%, P<0.05). Tumor growth was significantly inhibited in mice injected with Ad HTERTp-NK4, and the tumor growth inhibition rate was 47.3%, which was significantly higher than that in the controls (4.6%, P<0.05). CONCLUSION: Ad HTERTp-NK4 can inhibit tumor growth and decrease the invasive capacity of tumor cells, which makes it an ideal candidate for new gene therapy for colon carcinoma.