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Takeshi Tomonaga



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    MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Pathology
    • Presentations: 1
    • Now Available
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      MA18.09 - Protein Profiling of Small Lung Adenocarcinomas: An In-Depth Analysis (Now Available) (ID 1555)

      11:30 - 13:00  |  Author(s): Takeshi Tomonaga

      • Abstract
      • Presentation
      • Slides

      Background

      Among various cancers, lung cancer has one of the poorest prognoses, and adenocarcinoma is the most common histological subtype. Lung adenocarcinoma shows multistep progression from adenocarcinoma in situ (AIS) to invasive adenocarcinoma through minimally invasive adenocarcinoma (MIA). Recently, LC-MS/MS with multiple peptide labeling and a new fractionation method has made quantitative proteomic analysis feasible using small amounts of protein obtained by laser-microdissection. In this study, we performed quantitative protein profiling of AIS, MIA and early invasive lung adenocarcinoma and selected proteins that showed statistically significant differences in expression among them.

      Method

      Fresh tumor samples from five cases each of AIS, MIA and early invasive lung adenocarcinoma were collected by laser-microdissection, and proteins were extracted by the Phase Transfer Surfactant method. The samples were trypsinized, labeled with a TMT labeling kit, and fractioned with C18-SCX Stage Tip. Quantitative proteomic analysis was performed by LC-MS/MS (Q-Exactive plus) and analyzed with Proteome Discoverer software.

      Result

      A total of 4278 proteins were identified. Among them, the expression of 12 proteins – EEF1A2, CRABP2, NDRG1, NOL3, SCIN, DHCR24, CEACAM5, HIBADH, AK4, PIP4K2C, ASRGL1 and IFITM3 – was two-fold or higher in invasive adenocarcinoma than in AIS, and the expression increased gradually from AIS to invasive adenocarcinoma through MIA. Among these proteins, NDRG1 and AK4 are known to be related to hypoxia, whereas NOL3 and DHCR24 reportedly have an anti-apoptosis function.

      Conclusion

      Quantitative proteomic analysis of AIS, MIA and early invasive lung adenocarcinoma identified a total of 4278 proteins, 12 of which are thought to be associated with lung adenocarcinoma progression. These proteins may determine the grade of malignancy and could be potential targets for molecular therapy.

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