Abstract 3539
Background
Small Cell Lung Cancer (SCLC) is a highly metastatic form of lung cancer and the therapies remain unchanged since 40 years. Therefore, the discovery of novel transcriptomic alterations contributes to develop more effective targeted therapies. Among them, RLF/MYCL1 was described as a recurrent chimera implicated in tumor growth. The non-protein-coding RNA PVT1, linked to MYC expression, and its circular variant circPVT1 are also dysregulated in several malignancies and associated to tumor progression. Nevertheless, their functional and clinical role was only partially explored. We investigated these transcriptomic alterations in SCLC patients and cell lines, aiming at exploring a possible prognostic significance.
Methods
12 SCLC cell lines harboring MYC, MYCN or MYCL1 amplifications were tested by RNA-sequencing and RT-PCR for the recurrence of RLF/MYCL1. Moreover, the relative expression of PVT1/circPVT1 was evaluated by RT-qPCR. To investigate whether these transcriptomic alterations could serve as prognostic markers, overall survival (OS) and progression free survival (PFS) curves were plotted by Kaplan-Meier method according to the recurrence of RLF1/MYCL1 and the PVT1/circPVT1 expression levels in a cohort of 29 SCLC patients.
Results
RNA-seq analysis by ChimeraScan and FusionMap tools identified the occurrence of RLF/MYCL1 in four cell lines, showing the occurrence of two splicing variants originated by the fusion of RLF exon 1 to alternatively MYCL1 exon 2 (longer) or 3 (shorter). The longer variant was also found as recurrent in 16/28 (57.1%) SCLC patients, correlating with a shorter OS (median survival of 11 vs 17 months). Conversely, circPVT1 expression levels, according to the median expression of all SCLC samples, were associated with a better OS (median survival of 14 vs 8 months). No differences were found regarding the DFS and the recurrence of RLF1/MYCL1 or the PVT1/circPVT1 expression levels.
Conclusions
Our results confirmed the recurrence of the RLF/MYCL1 chimera in a high percentage of SCLC samples. Interestingly, our clinical investigations clearly disclosed that both the chimera and circPVT1 could be used as prognostic markers in SCLC, respectively negative and positive, although our results need to be confirmed in a wider cohort of patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
University of Bari, Italy.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3181 - Effects of Three Products in the Prevention and Treatment of Chemotherapy and Radiation Therapy-Induced Oral Mucositis
Presenter: Francesca Zannier
Session: Poster Display session 1
Resources:
Abstract
2433 - Boiling Histotripsy-induced Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers
Presenter: Cheol-Hee Shin
Session: Poster Display session 1
Resources:
Abstract
2663 - The bacterial receptor NOD2 mediates LGR5+ intestinal stem cells protection against irradiation via mitophagy activation
Presenter: Antonin Levy
Session: Poster Display session 1
Resources:
Abstract
3213 - Pulse mode irradiation regimen of PDT results in high progression free and overall survival in mice with model tumor
Presenter: Alexey Bogdanov
Session: Poster Display session 1
Resources:
Abstract
3722 - Proton-sensitizing effect of small molecule inhibitor of P300 histone acetyltransferase C646 in human pancreatic cancer cells.
Presenter: Sungwon Shin
Session: Poster Display session 1
Resources:
Abstract
5805 - Red-Blood-Cell-Membrane-Enveloped Magnetic Nanoclusters as a Biomimetic Theranostic Nanoplatform for Bimodal Imaging Guided Cancer Photothermal Therapy
Presenter: sheng wang
Session: Poster Display session 1
Resources:
Abstract
5251 - Urine cell-free and extracellular vesicle cargo miRNAs as biomarkers for prostate cancer diagnosis
Presenter: Ivan Zaporozhchenko
Session: Poster Display session 1
Resources:
Abstract
3657 - Parkin, APEX1 and BCL2L1 Tissue Expression in Southern Brazilian Patients with Different Breast Cancer Molecular Subtypes
Presenter: Bianca Cabral
Session: Poster Display session 1
Resources:
Abstract
2839 - Obesity and prognosis in breast cancer
Presenter: Noha Ibrahim
Session: Poster Display session 1
Resources:
Abstract
5132 - SIPA1 is a modulator of HGF induced tumor metastasis via the regulation of tight junctions in lung adenocarcinoma cells
Presenter: Chang Liu
Session: Poster Display session 1
Resources:
Abstract