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H. Nakamura
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P3.15 - SCLC/Neuroendocrine Tumors (ID 731)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.15-002 - Molecular Profiling and Networks Relevant to Disease Mechanisms in Small Cell Lung Cancer and Lung Carcinoid Tumor (ID 9823)
09:30 - 09:30 | Author(s): H. Nakamura
- Abstract
Background:
Small Cell lung cancer (SCLC), which belongs to neuroendocrine tumor (NT), is known for its highly aggressive clinical features and poor prognosis. The molecular underpinnings that may prognosticate survival and could increase our understanding of tumor development and progression are still poor understood in its highly aggressive malignancies. We aimed to describe the proteomic characteristics and biomarker profiling of high-grade NT, SCLC versus low-grade NT, carcinoid tumor (CT) by the state-of-the-art proteomics techniques utilizing clinical specimens.
Method:
In order to obtain the molecular-based differences between SCLC and CT, we performed proteomic analyses for these histological types in lung NTs. Based on definite histological diagnosis, cancerous cells were collected by laser microdissection from FFPE tissues of 6 patients each with SCLC and CT. To elucidate their protein expression profiles, a mass spectrometry-based quantitative proteomic analysis was conducted. After the different profiles were identified using a hierarchical clustering, we applied protein-protein interaction (PPI) network and gene-set enrichment analyses to assess how significantly proteins are expressed and which molecular pathways are activated in SCLC and CT.
Result:
A total of 1,991 proteins were identified from cancerous cell in FFPE tissues throughout these NT subtypes. By hierarchical clustering of the protein expression profiles, 12 cases were clearly classified into two groups of 6 SCLC and 6 CT. We finally identified 11 for SCLC and 44 for CT as tumor-specific proteins, respectively. In brief, our curation-based analysis of PPI networks built from proteins expressed significantly in SCLC cells has revealed that the activations of both mismatch repair system, and its resulted cell cycle pathway but suggested a fatal failure in disruption of mismatched DNA sequences, which suggested an occurrence of carcinogenesis progression simultaneously with an activity trying to return to normal, and which might suggest a heterogeneity of SCLC cells. Proteins expressed significantly in CT cells were the molecules known representatively as the biomarkers of NTs such as neurosecretory protein VGF, chromogranin-A, secretogranin-1 and -2. Besides those, we have found that the certain key network modules controlling cellular proliferation and apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage and repair, which also promotes cell transformation and tumorigenesis.
Conclusion:
Our clinical proteomic profiling of both SCLC and CT revealed their corresponding nature of aggressiveness and extent of prognosis, and detailed curation of PPI networks of interestingly suggested candidates of their therapeutic targets, which might reflect their disease mechanisms.
