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J.Y. Park
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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: 2
- 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): J.Y. Park
- 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.
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P3.04-079 - A Panel of Genetic Polymorphism Can Predict Prognosis in Lung Cancer (ID 168)
09:30 - 09:30 | Author(s): J.Y. Park
- Abstract
Background:
This study was conducted to investigate whether a panel of 8 genetic polymorphisms can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection.
Methods:
We selected 8 single nucleotide polymorphisms (SNPs) which have been associated with the prognosis of lung cancer patients after surgery in our previous studies. A total of 814 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the 8 SNPs with overall survival (OS) and disease-free survival (DFS) was analyzed.
Results:
The 8 SNPs (CD3EAP rs967591, TNFRSF10B rs1047266, AKT1 rs3803300, C3 rs2287845, HOMER2 rs1256428, GNB2L1 rs3756585, ADAMTSL3 rs11259927, and CD3D rs3181259) were significantly associated with OS and/or DFS. Combining those 8 SNPs, we designed a prognostic index to predict the prognosis of patients. According to relative risk of death, a score value was assigned to each genotype of the SNPs in the genetic model which best explains the association between genotypes and prognosis for each SNP. When we categorized the patients into two groups based on the prognostic index, high risk group was significantly associated with worse OS and DFS compared to low risk group (aHR for OS = 2.21, 95% CI = 1.69-2.88, P = 8.0 x 10[-9], and aHR for DFS = 1.58, 95% CI = 1.29-1.94, P = 1.0 x 10[-5]).
Conclusion:
Prognostic index using 8 genetic polymorphisms may be useful for the prognostication of patients with surgically resected NSCLC.
