Serum Amyloid A as a Predictive Marker for Radiation Pneumonitis in Lung Cancer Patients
To investigate serum markers associated with radiation pneumonitis (RP) grade ≥3 in patients with lung cancer who were treated with radiation therapy.
Methods and materials:
Pretreatment serum samples from patients with stage Ib-IV lung cancer who developed RP within 1 year after radiation therapy were analyzed to identify a proteome marker able to stratify patients prone to develop severe RP by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Dosimetric parameters and 3 biological factors were compared.
Serum samples from 16 patients (28%) with severe RP (grade 3-4) and 42 patients (72%) with no or mild RP (grade 0-2) were collected for analysis. All patients received a median of 54 Gy (range, 42-70 Gy) of three-dimensional conformal radiation therapy with a mean lung dose (MLD) of 1502 cGy (range, 700-2794 cGy). An m/z peak of 11,480 Da was identified by SELDI-TOF-MS, and serum amyloid A (SAA) was the primary splitter serum marker. The receiver operating characteristic area under the curve of SAA (0.94; 95% confidence interval [CI], 0.87-1.00) was higher than those of C-reactive protein (0.83; 95% CI, 0.72-0.94), interleukin-6 (0.79; 95% CI, 0.65-0.94), and MLD (0.57; 95% CI, 0.37-0.77). The best sensitivity and specificity of combined SAA and MLD for predicting RP were 88.9% and 96.0%, respectively.
Baseline SAA could be used as an auxiliary marker for predicting severe RP. Extreme care should be taken to limit the lung irradiation dose in patients with high SAA.
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ABSTRACT: PurposeAs tumor cells continuously evolve over time in response to host pressures. How tumor cells influenced by inflammatory tumor microenvironment with time are poorly defined. We hypothesized that prognostic biomarkers could be obtained by exploring the expression of inflammation-associated genes between early and late stage lung cancer tumor samples.Materials and Methods
Candidate inflammation-associated genes, APOC1, MMP1, KMO1, CXCL5, CXCL7, IL-1α, IL-1β, TNF-α and IL-6 were verified by real-time quantitative PCR (RT-qPCR). Gene expression profiles and immunofluorescence staining of 30 lung cancer tissue were compared.ResultsExpression of APOC1 and IL-6 mRNA on tumor tissue in late stage disease were significantly higher than early stage lung cancer patients. Immunofluorescence staining of tumor samples showed that expression of APOC1 gradually increased from early stage to late stage lung cancer patients. The expression levels of IL-6 and APOC1 in tumor samples were positively correlated; however, no prognostic value of APOC1 can be identified in serum samples.Conclusions
We found that the level of tumor APOC1 was highly expressed in late stage lung cancer. Further research is warranted to determine the molecular mechanisms underlying the cross-talk of APOC1 and IL-6 in tumor progression. An expanded sample size marker phase II study may likely lead to the discovery of new lung cancer therapeutics targeting APOC1.
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