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Y. Elshimali
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-074 - PD-L1 Gene Expression and Total Cell-Free RNA Measured in Blood Positively Differentiate Healthy Individuals from Metastatic NSCLC Patients (ID 2412)
09:30 - 09:30 | Author(s): Y. Elshimali
- Abstract
Background:
Cell-free DNA (cfDNA) released into the bloodstream by tumors allows non-invasive identification of tumor-specific mutations. However, not all molecular changes in tumors involve DNA mutations; in many cases it is also the quantity of a particular gene (i.e., gene expression) that is important. In this study, we investigated the use of cell-free RNA (cfRNA) released into the blood in order to monitor PD-L1 gene expression in NSCLC patients. The PD-1/PD-L1 pathway is a promising therapeutic target and anti-PD-L1 agents have shown encouraging activity in a variety of tumor types.
Methods:
Blood samples were collected from NSCLC patients at various times during therapy. Additionally, non-cancer bearing blood samples were obtained from healthy volunteers (“control group”). Plasma was fractionated from blood samples and nucleic acids were extracted. RNA was reverse-transcribed into cDNA using random primers, and then analyzed by quantitative RT-PCR using appropriate gene-specific primers. The cDNA of PD-L1 was quantitated in both cancer patients and the control group.. ERCC1 expression was also quantitated as an example of a non-tumor-specific gene. β-actin expression was used as the denominator gene representing total RNA.
Results:
PD-L1 expression was detected in the cfRNA of 60% (3/5 plasma samples) from the NSCLC patients, but was not detected in any samples from the control group (0/9), (p = 0.0005, Fisher’s Exact Test). ERCC1 expression was detected in 100% (5/5) of NSCLC patients and 67% (6/9) of the control group but its median expression value was about 8-fold higher in the plasma of cancer patients (p = 0.0045, Pearson’s chi-square). Median relative β-actin expressions in cancer patients and the control group were 19.3 (7.9-68.9) and 0.41 (0-0.75), respectively (p < 0.0062, Pearson chi-square) (Fig. 1). Figure 1
Conclusion:
These data demonstrate the potential value of using cfRNA from blood to measure gene expressions for detection of cancer and its recurrence, and in selecting and monitoring therapies. The presence of PD-L1 cfRNA in blood may be a specific indicator of cancer, although its sensitivity of tumor detection is less than 100% because it is not expressed in all cancer patients. ERCC1 expression, while not specific for tumors, nevertheless shows considerably higher overall levels in cancer patients. The surprisingly large (about 50-fold) difference in median total cfRNA between cancer patients and healthy individuals without any overlap in the ranges of expression suggests that total cfRNA may be useful as a sensitive preliminary indicator of the presence of cancer and for recurrence monitoring.
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P2.04-087 - Detection of Mutations from Peripheral Blood in Patients with Non-Small Cell Lung Cancer with Fast Turn-Around (ID 3083)
09:30 - 09:30 | Author(s): Y. Elshimali
- Abstract
Background:
In non-small cell lung cancer (NSCLC) several genetic changes that have clinical consequences for targeted treatment approaches have been identified. As for EGFR Mutations there are already options for more than one line of treatment. For those patients with secondary changes like the T790M-mediated resistance to EGFR inhibitors irreversible tyrosine kinase inhibitors (TKI) seem to be a promising alternative. These options may however be limited to missing proof of such changes as with progressing tumor burden patients may be susceptible to higher mortality with necessary invasive procedures. The so called “Liquid Biopsy” – using peripheral blood to obtain timely information on genetic information in solid malignancies – seems to be the urgently needed solution to this problem. Methods are needed that hold the promise of fast-turn around and broad availability.
Methods:
Serum was tested from 130 patients with adenocarcinoma or squamous cell cancer of the lung. All patients received at least one line of systemic therapy. Frequencies of EGFR ex19dels, EGFR L848R and EGFR T790M were tested as well as KRAS G12C, D and V. The detected frequencies were correlated with expected frequencies obtained from published data (mycancergenome.com). Furthermore the results from serum were correlated to results obtained from the available tumor tissue. Additional samples of fresh blood were tested.
Results:
Correlation of mutation detection results from serum correlated significantly with measurement of the available tumor specimen. Furthermore expected frequencies were in line with published occurrence of genetic changes. There was however a potential bias as T790M mutations were higher than expected which may be due to cancer center specific patient selection. These results were in line with the fresh blood samples tested. Turn-Around of fresh samples was three (3) days.
Conclusion:
Mutation detection is feasible from peripheral blood with fast turn-around and high sensitivity and specificity. In addition samples can be used either fresh or as stored serum probes. This will allow faster treatment decisions and higher patient satisfaction due to shorter intervals until start of therapy. The Liquid Biopsy is a clear and medically needed alternative to analyzing tissue samples. Especially in cases of secondary changes to tumors during systemic therapy this method will be crucial.
