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L. Antonangelo
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-029 - Detection of Sputum Cofilin-1 Protein for Diagnosis of Human Non-Small Cell Lung Carcinomas (ID 1269)
09:30 - 09:30 | Author(s): L. Antonangelo
- Abstract
Background:
The high incidence and mortality rates of lung cancer reflect the need for new diagnostic and prognostic markers capable to early detect the disease and also predict its recurrence. The ideal biomarker should be evaluated in biological samples obtained by minimally invasive procedures. In this context, sputum is an attractive biological sample for these tests since it may represent the field of injury. Because cell–extracellular matrix interactions participate in several steps required for tumor cell invasion and formation of metastases, cofilin-1, hyaluronic acid (HA) and CD44 have been targeted as potential useful tumor markers. To our knowledge, cofilin-1 has never been evaluated in sputum from lung cancer patients. Objective: To evaluate the diagnostic and prognostic role of sputum cofilin-1 and to the relationship between this biomarker with HA and its receptor (CD44) in patients with non small cell lung cancer (NSCLC).
Methods:
Cofilin-1 and CD44 were analyzed by Elisa immunoassay and HA by "Elisa-like" fluorometric assay in the sputum of 74 NSCLC patients, 13 cancer-free patients with obstructive lung disease and 8 healthy individuals. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression.
Results:
Sputum cofilin-1 levels were increased in patients with lung cancer (1475.83 pg/ml ±145.35) when compared to cancer-free patients (662.63 pg/ml ±5.74) and volunteers (415.25 ±3.68 pg/ml). A significant association was found between cancer patients with high levels of cofilin-1 and CD44 (R=0.21; P=0.04) as well as between HA and CD44 (R=0.46; P<0.01). Cofilin-1 did not correlate with HA (P>0.4). Univariate analysis demonstrated that high expression of sputum cofilin-1 significantly correlated to T4 (P=0.01) and M stage (P=0.03), tobacco history (P=0.01) and squamous cell carcinoma histologic type (P=0.04). Logistic regression analysis controlled for tobacco history, histologic types, stage, HA and CD44 expression showed that cancer cell–associated cofilin-1 was an independent predictor of metastases [OR=5.77 (0.78-42.74)]. Patients with sputum cofilin-1 >1475.83pg/ml had a high risk for metastasis. In relating to diagnosis, sputum Cofilin-1, at a cut off value of 248.9pg/mL presented sensitivity and specificity of 0.80 and 0.67 respectively, in distinguish healthy volunteers from NSCLC patients with AUC of 0.787. Cofilin-1 was also able to distinguish cancer-free patients from cancer patients at a cut off of 802.5pg/mL with AUC of 0.693 and respective sensitivity and specificity of 0.60 and 0.54.
Conclusion:
Cofilin-1 presented moderate sensitivity as diagnostic biomarker for lung cancer in sputum. Cofilin-1 was associated with metastases, but its prognostic value was dependent on the histological type and tobacco history. The association between sputum cofilin-1 and CD44 in cancer patients suggests that during tumor development, high levels of cofilin-1 facilitate tumors growth and the penetration of capillaries into the tissue milieu. Thus, increased tumor expression of cofilin-1 seems to be more associated to primary events, while increased angiogenesis seems to be related to a secondary event. Regardless of the involved mechanism, detection of sputum cofilin-1 provides important prognostic information on cancer patients. Larger series of NSCLC patients still needs to be studied to confirm the usefulness of sputum cofilin-1 as diagnostic and/or prognostic biomarker.
