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

Zhang XY, Zhang G, Jiang Y, Liu D, Li MZ, Zhong Q, Zeng SQ, Liu WL, Zeng MS - Chin J Cancer (2015)

Bottom Line: 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).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).Remarkably, in stages I-II patients, only CRP-SAA, not total SAA or CRP, showed significant association with overall survival in two cohorts.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. zhangxy@gzhmu.edu.cn.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Prognostic values of serum CRP-SAA, total SAA, and CRP in the retrospective cohort of lung cancer patients. a Kaplan–Meier survival curves of the 242 patients divided by the cutoff optical density (OD) value for CRP-SAA into low-level (OD ≤ 0.10) and high-level (OD > 0.10) groups. b Survival curves of 79 patients at stages I–II divided by the cutoff value for CRP-SAA into low- and high-level groups. c Survival curves of 163 patients at stages III-IV divided by the cutoff value for CRP-SAA into low- and high-level groups. d Survival curves of the 242 patients divided by the cutoff OD value for total SAA into low-level (OD ≤ 0.17) and high-level (OD > 0.17) groups. e Survival curves of 79 patients at stages I–II divided by the cutoff value for total SAA into low- and high-level groups. f Survival curves of 163 patients at stages III–IV divided by the cutoff value for total SAA into low- and high-level groups. g Survival curves of the 242 patients divided by the cutoff value for CRP into low-level (CRP ≤ 8 mg/L) and high-level (CRP > 8 mg/L) groups. h Survival curves of 79 patients at stages I–II divided by the cutoff value for CRP into low- and high-level groups. i Survival curves of 163 patients at stages III–IV divided by the cutoff value for CRP into low- and high-level groups. Significant differences were calculated using a log-rank test. The numbers of patients at risk at each specific time point are indicated. The number of events indicates the cumulative number of all events during the entire follow-up period. HR hazard ratio calculated by univariate Cox regression analysis, not adjusted by other factors. CI confidence interval.
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Fig4: Prognostic values of serum CRP-SAA, total SAA, and CRP in the retrospective cohort of lung cancer patients. a Kaplan–Meier survival curves of the 242 patients divided by the cutoff optical density (OD) value for CRP-SAA into low-level (OD ≤ 0.10) and high-level (OD > 0.10) groups. b Survival curves of 79 patients at stages I–II divided by the cutoff value for CRP-SAA into low- and high-level groups. c Survival curves of 163 patients at stages III-IV divided by the cutoff value for CRP-SAA into low- and high-level groups. d Survival curves of the 242 patients divided by the cutoff OD value for total SAA into low-level (OD ≤ 0.17) and high-level (OD > 0.17) groups. e Survival curves of 79 patients at stages I–II divided by the cutoff value for total SAA into low- and high-level groups. f Survival curves of 163 patients at stages III–IV divided by the cutoff value for total SAA into low- and high-level groups. g Survival curves of the 242 patients divided by the cutoff value for CRP into low-level (CRP ≤ 8 mg/L) and high-level (CRP > 8 mg/L) groups. h Survival curves of 79 patients at stages I–II divided by the cutoff value for CRP into low- and high-level groups. i Survival curves of 163 patients at stages III–IV divided by the cutoff value for CRP into low- and high-level groups. Significant differences were calculated using a log-rank test. The numbers of patients at risk at each specific time point are indicated. The number of events indicates the cumulative number of all events during the entire follow-up period. HR hazard ratio calculated by univariate Cox regression analysis, not adjusted by other factors. CI confidence interval.

Mentions: We evaluated whether CRP-SAA could be a prognostic marker for lung cancer. In the retrospective cohort, patients with high levels of CRP-SAA showed a shorter median survival than those with low levels of CRP-SAA (Fig. 4a). The 5-year overall survival (OS) rate was lower in the high-level group than in the low-level group (9.5% vs. 29.9%). When patients were stratified by cancer stages, a high level of CRP-SAA was also associated with a shorter median survival in the stages I–II (Fig. 4b) and stages III–IV subgroups (Fig. 4c; Table 4).Fig. 4


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

Zhang XY, Zhang G, Jiang Y, Liu D, Li MZ, Zhong Q, Zeng SQ, Liu WL, Zeng MS - Chin J Cancer (2015)

Prognostic values of serum CRP-SAA, total SAA, and CRP in the retrospective cohort of lung cancer patients. a Kaplan–Meier survival curves of the 242 patients divided by the cutoff optical density (OD) value for CRP-SAA into low-level (OD ≤ 0.10) and high-level (OD > 0.10) groups. b Survival curves of 79 patients at stages I–II divided by the cutoff value for CRP-SAA into low- and high-level groups. c Survival curves of 163 patients at stages III-IV divided by the cutoff value for CRP-SAA into low- and high-level groups. d Survival curves of the 242 patients divided by the cutoff OD value for total SAA into low-level (OD ≤ 0.17) and high-level (OD > 0.17) groups. e Survival curves of 79 patients at stages I–II divided by the cutoff value for total SAA into low- and high-level groups. f Survival curves of 163 patients at stages III–IV divided by the cutoff value for total SAA into low- and high-level groups. g Survival curves of the 242 patients divided by the cutoff value for CRP into low-level (CRP ≤ 8 mg/L) and high-level (CRP > 8 mg/L) groups. h Survival curves of 79 patients at stages I–II divided by the cutoff value for CRP into low- and high-level groups. i Survival curves of 163 patients at stages III–IV divided by the cutoff value for CRP into low- and high-level groups. Significant differences were calculated using a log-rank test. The numbers of patients at risk at each specific time point are indicated. The number of events indicates the cumulative number of all events during the entire follow-up period. HR hazard ratio calculated by univariate Cox regression analysis, not adjusted by other factors. CI confidence interval.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4593389&req=5

Fig4: Prognostic values of serum CRP-SAA, total SAA, and CRP in the retrospective cohort of lung cancer patients. a Kaplan–Meier survival curves of the 242 patients divided by the cutoff optical density (OD) value for CRP-SAA into low-level (OD ≤ 0.10) and high-level (OD > 0.10) groups. b Survival curves of 79 patients at stages I–II divided by the cutoff value for CRP-SAA into low- and high-level groups. c Survival curves of 163 patients at stages III-IV divided by the cutoff value for CRP-SAA into low- and high-level groups. d Survival curves of the 242 patients divided by the cutoff OD value for total SAA into low-level (OD ≤ 0.17) and high-level (OD > 0.17) groups. e Survival curves of 79 patients at stages I–II divided by the cutoff value for total SAA into low- and high-level groups. f Survival curves of 163 patients at stages III–IV divided by the cutoff value for total SAA into low- and high-level groups. g Survival curves of the 242 patients divided by the cutoff value for CRP into low-level (CRP ≤ 8 mg/L) and high-level (CRP > 8 mg/L) groups. h Survival curves of 79 patients at stages I–II divided by the cutoff value for CRP into low- and high-level groups. i Survival curves of 163 patients at stages III–IV divided by the cutoff value for CRP into low- and high-level groups. Significant differences were calculated using a log-rank test. The numbers of patients at risk at each specific time point are indicated. The number of events indicates the cumulative number of all events during the entire follow-up period. HR hazard ratio calculated by univariate Cox regression analysis, not adjusted by other factors. CI confidence interval.
Mentions: We evaluated whether CRP-SAA could be a prognostic marker for lung cancer. In the retrospective cohort, patients with high levels of CRP-SAA showed a shorter median survival than those with low levels of CRP-SAA (Fig. 4a). The 5-year overall survival (OS) rate was lower in the high-level group than in the low-level group (9.5% vs. 29.9%). When patients were stratified by cancer stages, a high level of CRP-SAA was also associated with a shorter median survival in the stages I–II (Fig. 4b) and stages III–IV subgroups (Fig. 4c; Table 4).Fig. 4

Bottom Line: 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).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).Remarkably, in stages I-II patients, only CRP-SAA, not total SAA or CRP, showed significant association with overall survival in two cohorts.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R. China. zhangxy@gzhmu.edu.cn.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus