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Y. Dong
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-103 - Evaluation of the TGF Beta Superfamily Member Activin-A as a Novel Circulating Prognostic Marker in Lung Cancer (ID 2720)
09:30 - 09:30 | Author(s): Y. Dong
- Abstract
Background:
Identification of biomarkers that can facilitate early detection and therapeutic decision making in lung cancer (LC) is urgently needed. Growth factors of the activin family are deregulated in a number of malignancies including thoracic tumors. Recent studies provided data regarding the tumor tissue expression levels of activin-A in lung adenocarcinoma (ADC): High activin-A expression was associated with poor prognosis, enhanced metastasis and shorter progression-free survival in stage I ADC. Since activin-A is secreted to the circulation and can be detected in plasma, this study aims to determine, for the first time, the value of circulating activin-A as a biomarker in LC patients.
Methods:
Plasma samples from patients with small cell lung cancer (SCLC, n= 79), ADC (n=87) and squamous cell carcinoma (n=36) were collected between 2009 and 2013 at the time of diagnosis or before surgical resection. Additional samples, serving as age- and sex-matched controls, consisted of individuals without malignancies (n=66). Measurement of samples was performed using the Quantikine activin-A Elisa kit (R&D Systems) and all statistical analyses were performed using the PASW Statistics 20.0 package and GraphPad Prism 6.0.
Results:
Mean plasma activin-A levels (PAL) (pg/ml) were the following: 628,8±38,42 (ADC, range: 112,4-1875), 613,5±68,22 (SCC, range: 194-2076), 771±77,06 (SCLC, range: 174,1-3627) and 433,3±16,27 (controls, range: 194,1-808,8). A gender-related variation in the PAL of controls (female (n=31, mean PAL 469,5±24,54 (range 212,95-808,79)) vs. male (n=35; mean PAL 401,3±20,49 (range 194,1-759,02)), p= 0.0319) was observed. PAL was significantly increased in patients with ADC (p=0.0009), SCC (p=0.0061) and SCLC (p<0.0001) compared to controls. There was no difference in PAL with regard to patients´ age, gender, BMI, smoking status or other co-morbidities in all 3 LC types. A significant TNM stage-dependent increase of PAL was observed in all 3 LC types. PAL was elevated in T3 SCC, in T4 ADC and in T3 and T4 SCLC. PAL was also clearly associated with N status and metastatic disease in all 3 LC types. Importantly, in case of SCLC, PAL was associated with extensive disease and showed metastatic site specificity. In ADC patients, elevated PAL was associated with significantly worse overall survival (OS) (p<0.0001). Of note, in locally advanced ADC, elevated PAL also proved to be a significant negative prognosticator (p=0.048). Moreover, elevated PAL was associated with a poor OS in SCLC patients (p=0.0009). Multivariate analysis revealed that PAL was an independent prognostic factor in ADC and SCLC patients. Survival and multivariate analysis data of the SCC cohort will be presented at the conference. ROC curve analysis showed an AUC of 0.691 in SCLC and an AUC of 0,657 in ADC for PAL.
Conclusion:
Our findings suggest that PAL is significantly elevated in a disease stage-dependent manner in LC patients. Moreover, elevated PAL is associated with poor prognosis in ADC and SCLC patients.
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P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.08-007 - Fibulin-3: A Potential Prognostic Biomarker in Malignant Pleural Mesothelioma? (ID 1668)
09:30 - 09:30 | Author(s): Y. Dong
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is a highly aggressive asbestos-induced cancer arising from the mesothelium lining the thoracic cavities. The definitive diagnosis of MPM in most instances depends on the availability of a biopsy. A number of biomarkers have been proposed to assist in making the MPM diagnosis but none of them has yet reached the accuracy required for routine clinical use. Among the candidates is the secreted extracellular glycoprotein Fibulin-3 (FBLN3) (Pass et al, NEJM 2012; 367(15)). In this study, we have further investigated the potential of FBLN3 to serve as a biomarker for MPM.
Methods:
Cellular and secreted FBLN3 was measured (ELISA) in MPM and normal mesothelial cell lines, plasma of xenograft tumour-bearing mice, plasma from two independent series of MPM and non-MPM patients, and in malignant and non-malignant pleural effusions. The diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and the Kaplan-Meier method, respectively.
Results:
FBLN3 levels were significantly higher in MPM cells than in mesothelial cells, with a strong correlation between secreted and cellular levels. Human FBLN3 was also detectable in the plasma of tumour-bearing mice, suggesting that MPM cells were the origin of circulating FBLN3. Plasma FBLN3 levels found in MPM patients were lower than previously reported (Pass et al, NEJM 2012; 367(15)), but were comparable to those appearing in subsequent validation studies (Creaney et al, Thorax 2014; 69(10), Corradi et al, Anticancer Res 2013; 33(12)). Plasma FBLN3 was significantly elevated in MPM patients from a Sydney cohort, but far less in a Vienna cohort and the diagnostic accuracy of FBLN3 was insufficient in both cohorts [63%, (95%CI: 50.1-76.4) and 56% (95%CI: 41.5-71.0), respectively]. FBLN3 levels found in pleural effusions were comparable to those reported in previous studies, but the difference between cases and controls did not reach significance. In our series low levels of pleural effusion FBLN3 were again associated (p=0.002) with prolonged survival. In multivariate analysis taking histological subtype, age and gender into account FBLN3 remained significant with a hazard ratio of 9.92 (95%CI: 2.14–45.93).
Conclusion:
FBLN3 is overexpressed in MPM cell lines and may point to a potential oncogenic role for this protein. In contrast to the initial report linking FBLN3 to diagnosis in MPM, the levels of FBLN3 measured in plasma and pleural fluid of our series of MPM patients lacked diagnostic accuracy. However, the potential prognostic value of FBLN3 levels measured in pleural fluid was confirmed and in line with previous validation studies. These data underline the importance of validation studies for newly proposed biomarkers.
