Virtual Library
Start Your Search
Anna Grenda
Author of
-
+
P1.11 - Screening and Early Detection (Not CME Accredited Session) (ID 943)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
-
+
P1.11-03 - MicroRNA with Ability to Reciprocal Regulation of Dicer and Drosha – Plasma Expression Status and Diagnostic Value in Non-Small Cell Lung Cancer (ID 12133)
16:45 - 18:00 | Author(s): Anna Grenda
- Abstract
Background
Examination of microRNAs expression in plasma could be useful in screening and in early detection of non-small cell lung cancer (NSCLC). One of the most important enzymes in miRNA biogenesis are Dicer and Drosha. Disrupted expression of miRNA with ability to reciprocal regulation of Dicer and Drosha could participate in cancer development.
a9ded1e5ce5d75814730bb4caaf49419 Method
Plasma expression of miR-27-3p, miR-31, miR-182 and miR-195 were analysed in 138 Polish NSCLC patients (median age 65 years, 83 male and 55 female) and in 45 healthy people (median age 62 years, 28 male and 17 female). 57 (41.3%) NSCLC patient were in I-IIIA stage and 81 (58.7%) patients were in IIIB-IV stage. Relative expression of microRNAs between studied groups was compared using U Mann-Whitney test. For assessment of diagnostic accuracy (test sensitivity and specificity), the receiver operating curves (ROC) with area under curve (AUC) analysis were generated.
4c3880bb027f159e801041b1021e88e8 Result
We demonstrated that plasma levels of miR-27-3p, miR-31 and miR-182 were significantly higher (p<0.000001, p=0.00008, p=0.006 respectively) and miR-195 significantly lower (p=0.000002) in NSCLC patients in comparison with healthy donors. Moreover, patients with early stages (I-IIIA) of NSCLC showed significantly higher expression of miR-27a-3p (p<0.000001), miR-31 (p=0.0003) and miR-182 (p=0.000003) than healthy persons. Expression of miR-195 was significantly lower in patients with early stages (I-IIIA) of NSCLC than in healthy donors (p<0.000001). AUC for miR-27a was 0.95 (94% sensitivity and 81% specificity, p<0.00001), for miR-31 was 0.71 (73% sensitivity and 61% specificity, p=0.001), for miR-182 was 0.77 (70% sensitivity and 79% specificity, p<0.00001) and for miR-195 was 0.82 (74% sensitivity and 80% specificity, p=0.00001).
8eea62084ca7e541d918e823422bd82e Conclusion
Expression of miR-27a, miR-31, miR-182 and miR-195 could distinguish patients with NSCLC from healthy people. The examination of these microRNAs in plasma could be used in non-invasive lung cancer diagnosis. Deregulation of Dicer and Drosha expression by microRNAs could have oncogenic character.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.04-05 - Correlation Between PD-L1 Gene Promoter Polymorphisms and Expression of PD-L1 mRNA and Protein in NSCLC Patients. (ID 12554)
16:45 - 18:00 | Author(s): Anna Grenda
- Abstract
Background
Immunotherapy, the most novel approach to cancer treatment, gives a promising option for non-small cell lung cancer (NSCLC) patients. Most drugs targeting PD-1 or PD-L1 have been proven to be effective when cancer tissue expresses PD-1 or PD-L1 protein on its surface. The promoter region of PD-L1 gene is responsible for regulating the gene expression, thus in effect the expression of the protein. We decided to check whether single nucleotide polymorphisms (SNPs) in PD-L1 gene promoter region may affect this expression.
a9ded1e5ce5d75814730bb4caaf49419 Method
The study included 47 NSCLC patients (20 male, 27 female; median age 65±7.6 ). PD-L1 protein expression was analysed using two IHC assays with SP142 and 22C3 antibodies, on corresponding analysis platforms. mRNA was analysed using qRT-PCR method. PD-L1 gene promoter region polymorphisms [rs822335(C/T) and rs822335(C/G)] were analysed using real-time PCR method, on Illumina Eco platform. The analysis was performed in histological (resected tissue) and cytological (cellblocks from bronchoscopy biopsies) material (FFPE blocks).
4c3880bb027f159e801041b1021e88e8 Result
There were significant positive correlations between expression of mRNA of PD-L1 gene and the percentage of PD-L1 protein positive cells: tumor cells in the reaction with 22C3 antibody (R=+0.39,p=0.025), tumor cells in the reaction with SP142 antibody (R=+0.45, p=0.009) as well as infiltrating immune cells in the reaction with SP142 antibody (R=+0.49, p=0.006).
The studied group consisted of 21 CC homozygotes, 23 CT heterozygotes and 3 TT homozygotes in rs822335, and 12 CC homozygotes, 24 CG heterozygotes and 11 GG homozygotes in rs822336 polymorphic sites.
Slightly higher (p=0.08) percentage of tumor cells with PD-L1 expression was observed in patients with CC genotype compared to patients with CT and TT genotypes in rs822335 polymorphism. We observed significantly higher expression of mRNA for PD-L1 gene in patients with GG genotype compared to patients with CG genotype (p=0.05) in rs822336 polymorphism. Additionally, odds ratio analysis showed that a higher chance of high mRNA expression of PD-L1 gene occurred in patients with GG genotype as compared to patients with CC genotype (OR=7.0, ch2=4.46, p=0.035).
8eea62084ca7e541d918e823422bd82e Conclusion
Analysis of PD-L1 expression on tumor cells presents numerous problems – availability of material, tumor heterogeneity, different methods of detection. We have presented that analysis of PD-L1 gene promoter polymorphisms may be useful in determination of PD-L1 expression. It might be carried out in blood samples, when surgical material is not available. The usefulness of PD-L1 gene polymorphism, as a predictor of immunotherapy, should be investigated in clinical trials.
6f8b794f3246b0c1e1780bb4d4d5dc53
