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Y. He
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MINI 12 - Biomarkers and Lung Nodule Management (ID 109)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:J.M. Siegfried, H.I. Pass
- Coordinates: 9/07/2015, 16:45 - 18:15, 401-404
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MINI12.03 - Comprehensive Analysis of MicroRNA Expression Patterns in Lung Adenocacinoma Presenting with GGNs and Non-Tumorous Tissues (ID 701)
16:55 - 17:00 | Author(s): Y. He
- Abstract
- Presentation
Background:
Lung cancer is the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for about 80% of primary lung cancer cases and approximately two thirds of them are diagnosed at an advanced stage . The poor prognosis of this disease is partially due to the lack of an effective means of early diagnosis. Discovery of an effective and reliable tool for early diagnosis of lung cancer would play a pivotal role in improving the prognosis of patients with lung cancer. Pulmonary ground-glass nodules (GGNs) are increasingly detected in clinical practice. GGNs are related to lung cancer, especially lung adnocacinoma . The subject of how to manage the pulmonary GGNs remains controversial. It is necessary to identify biological markers that can be used to screen high-risk patients in order to allow better lung adenocacinoma presenting with GGNs detection, earlier intervention and increase the likelihood of successful treatment. MicroRNAs are small non-coding RNAs of 18–24 nucleotides, typically excised from 60–110 nucleotide foldback RNA precursor structures . MicroRNAs have drawn significant attention in cancer research after it was linked to oncogenesis and tumor metastasis. Abnormal expression of microRNAs has been found in both haematopoietic and solid tumours by various genome-wide techniques. There is no report about the relationship between microRNA and pulmonary GGNs. It is necessary to identify biological markers that can be used to screen high-risk patients presenting GGNs in order to allow early lung adenocacinoma detection. Our study investigated microRNA expression with the intention to identify a panel of microRNAs for the diagnosis of lung adenocarcinoma presenting with GGNs.
Methods:
73 pairs of samples (tumorous and non-tumorous) were surgically resected from lung adnocacinoma patients presenting with GGNs from Shanghai Pulmonary Hospital between May 2012 and June 2014. After obtaining the approval of the patient consent, fresh tissues samples were taken during surgical resection, snap-frozen on dry ice and stored at−80◦C. MicroRNA expression of tumor and non-tumorous tissues was investigated in 3 participants by the next generation sequencing. Then, we analyzed the difference expression microRNA profiles which were identified by second generation sequencing in 73 pairs of lung adenocacinoma presenting with GGNs and adjacent non-tumorous tissues using a quantitative reverse-transcriptase polymerase chain reaction assay (qRT-PCR).
Results:
When we compared microRNA expression among lung cancer tissues versus corresponding noncancerous lung tissues via next-generation sequencing, 23 microRNAs had statistical differences in expression between groups. Five microRNAs (hsa−miR−548ar−5p, chr10_7330_star, chr17_10932_star, hsa−miR−148a−3p, hsa−miR−210−3p) exhibited higher expression in the adnocacinoma samples than that in the non-tumorous samples, eighteen microRNAs (hsa−miR−548x−5p, hsa−miR−144−3p, hsa-miR-106a-5p, hsa−miR−548ay−5p, hsa−miR−199a−3p, hsa−miR−378d, hsa−miR−4732−3p, hsa−miR−486−3p, chr7_5517, hsa−miR−1307−5p, chr17_10880, hsa−miR−127−3p, hsa−miR−411−5p, chr1_1402, chr16_10269, hsa−miR−138−5p, hsa−miR−212−3p, hsa−miR−33b−5p) demonstrated lower expression in adnocacinoma samples than that in the non-tumorous samples (P＜0.05). Further validated by qRT-PCR, six microRNAs (chr17_10932_star, hsa−miR−148a−3p, hsa−miR−210−3p, chr1_1402, hsa−miR−378d, hsa−miR−138−5p) were statistically differentially expressed in tumorous compared with non-tumorous tissues.
Conclusion:
We found a microRNA panel that has considerable clinical value in diagnosing lung adenocacinoma presenting with GGNs. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy.
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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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P3.04-010 - EML4-ALK Fusion Detected by qRT-PCR Confers Similar Response to Crizotinib as Detected by FISH in Patients with Advanced NSCLC (ID 2338)
09:30 - 09:30 | Author(s): Y. He
- Abstract
Background:
Quantitative reverse transcriptase polymerase chain reaction assay (qRT-PCR) has been proved to have high sensitivity and specificity to detect anaplastic lymphoma kinase (ALK) rearrangements. The aim of this study was to investigate the response to crizotinib in patients of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements detected by qRT-PCR.
Methods:
Patients with advanced NSCLC who had their ALK rearrangement status detected by qRT-PCR were included in this analysis. The utility of qRT-PCR and fluorescence in situ hybridization assay (FISH) were compared in patients who were treated with crizotinib based on their positive ALK rearrangements.
Results:
1010 patients were included in this study. Among them, 104 patients were ALK qRT-PCR positive and 53 of them received crizotinib treatment. Among 255 tumors simultaneously analyzed by FISH and RT-PCR, the latter successfully detected all the 25 tumors with arrangements, including two cases which were missed by FISH. The overall response rate (ORR) and median progression free survival (mPFS) of the 53 patients with ALK rearrangements who received crizotinib treatment were 60.4% (95%CI, 47.2-73.6) and 8.4 months (95% CI 6.75-10.05) respectively, which were similar to the 21 patients detected by FISH with ORR of 57.1% (95% CI 33.3-76.2) (p=0.799) and mPFS of 7.4 months (95% CI 4.43-10.38) (p=0.833) after crizotinib treatment. Interestingly, there were 2 patients responded to crizotinib had their ALK rearrangement detected by qRT-PCR but not FISH.
Conclusion:
qRT-PCR should be considered as an alternative assay to detect ALK fusion oncogene in NSCLC patients who might be benefit from crizotinib treatment.
