Author of

• 15382

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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)

  • 15485

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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): P. Stockhammer
    • 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.