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S.K. Do
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P1.06 - Poster Session/ Screening and Early Detection (ID 218)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.06-008 - Functional Polymorphisms in PD-L1 Gene Are Associated with the Prognosis of Patients with Early Stage Non-Small Cell Lung Cancer (ID 1124)
09:30 - 09:30 | Author(s): S.K. Do
- Abstract
Background:
This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection.
Methods:
Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. A total of 354 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the SNPs with overall survival (OS) was analyzed.Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. A total of 354 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the SNPs with overall survival (OS) was analyzed.
Results:
Among the 12 SNPs investigated, PD-L1 SNP1C>G, SNP2G>C, and SNP3T>A were significantly associated with worse survival outcomes in multivariate analyses. When the three SNPs were combined, OS decreased in a dose-dependent manner as the number of bad genotypes increased (Ptrend = 0.0003). A higher expression of the reporter gene for the SNP2G- SNP3T haplotype was observed compared with the SNP2C- SNP3A haplotype by luciferase assay (P = 0.004). Patients with higher expression of PD-L1 mRNA had a better survival compared with lower expression (P = 0.03).
Conclusion:
PD-L1 SNP1C>G, SNP2G>C, and SNP3T>A polymorphisms may be useful for the prediction of prognosis in patients with surgically resected NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the antitumor immunity.
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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)
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P3.04-068 - A Genetic Variation in a microRNA Target Site of ETS2 Gene Is Associated with Clinical Outcome of Chemotherapy in Non-Small Cell Lung Cancer (ID 2904)
09:30 - 09:30 | Author(s): S.K. Do
- Abstract
Background:
Genetic polymorphisms in miRNAs or their target sites may affect miRNA-mRNA interactions, leading to altered expression of target genes. Recently, crosslinking, ligation, and sequencing of hybrids (CLASH) provided direct observation of transcriptome-wide miRNA-target pairs. The present study was performed to investigate the association of single nucleotide polymorphisms (SNPs) located in the miRNA target sites, which were experimentally verified by CLASH, with the clinical outcome of chemotherapy in advanced non–small cell lung cancer (NSCLC).
Methods:
Ninety eight SNPs in miRNA target sites of cancer related genes were selected from 18,500 miRNA:target interactions in CLASH data, and investigated in 384 advanced NSCLC patients who received first-line paclitaxel-cisplatin chemotherapy, using a sequenom mass spectrometry-based genotype assay.
Results:
Of the 98 SNPs analyzed, 17 SNPs were significantly associated with the clinical outcome after chemotherapy. Among these, ANAPC1 rs3814026C>T, ETS2 rs461155A>G, and SORBS1 rs7081076C>A were found to be associated with both chemotherapy response and survival. Notably, the relative expression level of ETS2 was significantly associated with rs461155A>G genotypes in both tumor and paired normal lung tissues (Ptrend = 4 x 10[-7], and 0.0003, respectively).
Conclusion:
These findings suggest that the three SNPs, especially ETS2 rs461155A>G, could be used as biomarkers predicting the response and survival of NSCLC patients treated with first-line paclitaxel-cisplatin chemotherapy.
