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M. Nicoś
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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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P1.06-007 - Plasma Circulating MicroRNA-944 and MicroRNA-3662 as Novel Histologic Type-Specific Lung Cancer Biomarkers (ID 521)
09:30 - 09:30 | Author(s): M. Nicoś
- Abstract
Background:
Altered expression of microRNAs is associated with development and invasion of cancers by regulating post-transcriptionally gene function. Possibility of detection of circulating miRNAs expression in patients’ plasma or serum make them valuable biomarkers of different neoplasms, such as lung cancer.
Methods:
We investigated potential role of miR-944 and miR-3662 expression analysis as a novel lung cancer biomarkers and their lung tumor specificity in plasma samples of 90 lung cancer patients (40 NSCLC patients in stage IA-IIIA and 20 NSCLC patients in stage IIIB-IV; 8 SCLC patients with limited and 22 SCLC patients with extensive disease) and 85 healthy individuals using qRT-PCR analysis.
Results:
Expression of miR-944 and miR-3662 was significantly upregulated in lung cancer patients in comparison to healthy individuals. Higher stage of lung cancer correlated with higher miRNAs expression (Figure 1). Receiver operating curves (ROC) analysis have presented diagnostic power of analysis of both miRNAs expression for detection of patients with I and II stage of NSCLC with area under curve (AUC) of 0.881. Moreover, miR-944 has shown diagnostic accuracy for operable squamous cell carcinoma detection (AUC=0.982) whereas miR-3662 - for operable adenocarcinoma (AUC=0.926) (Figure 2).Figure 1Figure 2
Conclusion:
Our research is a first study investigating the plasma expression of miR-944 and miR-3662 in patients with neoplasms and in healthy individuals. Moreover, this is a first study that described a miR-3662 expression. We have shown that examination of these two miRNAs may be considered as a tool for NSCLC early diagnosis as well as for non-invasive diagnosis of lung cancer late stages. Studied miRNAs have also shown high utility in detection of histological type-specific NSCLC subtypes, such as adenocarcinoma and squamous-cell carcinoma.
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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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P3.04-033 - Screening for Driver Mutations in Caucasian Patients with Central Nervous System Metastases of Non-Small-Cell Lung Cancer (ID 1047)
09:30 - 09:30 | Author(s): M. Nicoś
- Abstract
Background:
The knowledge about molecular profile of advanced NSCLC may increase the possibility and effectiveness of cancer treatment. According to data of LCMC, FNN and CRUK, driver mutations are reported in 50-60% of non-small cell lung cancer (NSCLC) patients, especially in adenocarcinoma subtype. Unfortunately, we have limited information concerning the incidence of driver mutations in metastatic lesions of NSCLC. The main aim of the study was characterize the molecular background of central nervous system (CNS) metastatic lesions of NSCLC. It was performed by estimation the frequency of selected driver mutations in Caucasian chemotherapy and molecularly targeted therapy naïve patients.
Methods:
The studied group included 145 patients (45 females, 100 males, age: 60±8,8 years) with CNS metastases of NSCLC.The studied group included 80 adenocarcinomas, 29 squamous-cell carcinomas, 22 large-cell carcinomas and 14 not otherwise specified patients. 36 patients were non-smokers. In 30 patients the material was simultaneously available from primary and metastatic NSCLC tumors. The molecular profile of driver mutations was determined in EGFR, KRAS, NRAS, BRAF, PIK3CA, HER2, and DDR2 genes. Mutations were screened in DNA isolated from formalin-fixed paraffin-embedded tissue samples using the quantitative real-time PCR technique with commercially available molecular kits. The driver mutations presence was confirmed by DNA sequencing, multiple single-strand conformation polymorphism (MSCCP) and other PCR techniques.
Results:
The driver mutations were identified in 52/145 (36%) of patients with CNS metastases (Fig.1), significantly more frequent in adenocarcinoma (p= 0.05, χ[2]= 3.817), patients and non-smokers (p= 0.004, χ[2]= 8.131). Only one patient had doublet mutations in DDR2 and KRAS genes. In corresponding primary tumors we detected 10/30 (33%) mutations in KRAS gene (7/30, 23%) and EGFR gene (3/30, 10%). However, 5 KRAS mutations were identified both in primary and metastatic lesions, while 1 mutation was detected only in primary tumor and 1 mutation - only in the metastatic tumor.
Conclusion:
Analysis of molecular profile confirmed assumptions that driver mutations could be detected both in primary and CNS metastatic tumors of NSCLC. Therefore, both primary and metastatic tumor samples could be considered as a representative for molecular testing in patients with metastatic cancer. Figure 1
