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R. Langfort
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-004 - The Methylation Profiling of Multiple Tumor Suppressor Genes in Plasma Cell-Free DNA of Patients with NSCLC vs Benign Tumors (ID 5166)
14:30 - 14:30 | Author(s): R. Langfort
- Abstract
Background:
Effective discrimination between lung cancer and benign tumours is a common clinical problem in the differential diagnosis of solitary pulmonary nodules. While most solitary pulmonary nodules are benign, around 20% of cases represent an early stage lung cancer. The presence of cell-free DNA (cfDNA) in plasma of lung cancer patients demonstrates promising diagnostic implications and could be considered as an auxiliary tool in the differential diagnosis of solitary pulmonary nodules by evaluating cancer-specific biomarkers, such as hypermethylated tumor DNA fragments. We developed a simultaneous methylation profiling of 21 distinct tumor suppressor genes (TSGs) in plasma cfDNA using MS-MLPA assay.
Methods:
The methylation profiling of 21 TSGs in plasma cfDNA of 32 resectable NSCLC (I-IIIa) patients and 8 subjects with benign lung nodules (hamartoma, fibrosis, granuloma) was performed using optimized MS-MLPA assay.
Results:
25/32 (78%) NSCLC and 8/8 (100%) benign-nodule cfDNA samples presented at least one TSG methylation, however the number of hypermethylated TSGs was much higher in NSCLC group. APC (frequency 18% samples), MLH1 (18%), ATM (13.6%), DAPK1 (13.6%), HIC 1 (13.6%), and RARβ (9%) were the most frequently methylated genes in NSCLC, while TIMP3 (75%), MLH1 (25%) and TP73 (37.5%) – in benign patients.
Conclusion:
The optimized MS-MLPA assay allowed simultaneous detection of multiple methylated TSGs in plasma cfDNA. The MS-MLPA showed good performance in samples with diverse cfDNA concentrations suggesting that methylation detection rate depends on the methylated DNA content in a sample. The study is on-going. The groups are to be extended and other benign lung pathologies evaluated.
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P2.01-079 - The Serum Levels of Alpha-1 Antitrypsin Are Strongly Associated with Its Local Production by Tumor Cells in NSCLC Patients (ID 5438)
14:30 - 14:30 | Author(s): R. Langfort
- Abstract
Background:
Lung cancer and chronic obstructive pulmonary disease (COPD) share a common etiology. Despite the known associations of alpha-1 antitrypsin (AAT) deficiency with COPD and COPD with lung cancer, few studies examined the association of AAT and lung cancer. We have investigated AAT serum levels in PiMM non-small cell lung cancer (NSCLC) patients with respect to PiMM controls with COPD and benign lung nodules since AAT is an acute-phase protein. The AAT tumor tissue expression was analyzed in NSCLC group to evaluate the potential contribution of cancer cells in AAT production.
Methods:
Serum and matched FFPE tissue samples were collected from 194 NSCLC patients (stages I-IV) with PiMM phenotype of AAT. The serum concentrations of AAT and CRP were measured by nephelometry. The AAT protein expression in NSCLC tumor cells was assessed by immunohistochemistry. Reference groups consisted of 183 PiMM COPD and 50 PiMM patients with benign lung nodules (hamartoma, tuberculoma, granuloma and other).
Results:
In NSCLC patients mean AAT serum concentration (195.5 mg/dl) was significantly higher than in COPD group (171 mg/dl) and patients with benign lung nodules (154 mg/dl; p<0.0001). AAT concentration was significantly higher in SQC type (202 mg/dl) than ADC (175 mg/dl; p<0.029) patients, and in advanced (IIIb-IV, 247 mg/dl) versus early stage disease (I-IIIa, 190 mg/dl, p<0.0001). AAT levels significantly correlated with CRP (R=0.6; p<0.0001), however CRP level did not differentiate NSCLC from COPD. Importantly, the strong AAT expression observed in tumor tissue was positively associated with the higher AAT blood levels, while weak or no AAT expression directly correlated with the lower AAT blood levels (p<0.0079).
Conclusion:
We have demonstrated for the first time that the local production of AAT by tumor cells significantly contributes to the high levels of AAT in blood of NSCLC patients. The significant association of serum AAT levels with stage and histology of NSCLC may implicate clinical use of AAT as a biomarker or therapeutic target.
