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A. Hoffmann
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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: 1
- 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): A. Hoffmann
- 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.
