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Tomohito Saito



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    MA24 - Genomic Evolution, KEAP 3 and More Non-Coding RNA (ID 928)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 10:30 - 12:00, Room 205 BD
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      MA24.03 - Biologic Profiling of Pre-Metastatic Niche in Completely Resected Pathological Stage I Non-Small Cell Lung Cancer (ID 13081)

      10:40 - 10:45  |  Presenting Author(s): Tomohito Saito

      • Abstract
      • Presentation
      • Slides

      Background

      Despite refinement of treatment strategy for non-small cell lung cancer (NSCLC), pathological Stage I NSCLC still develops recurrent disease in approximately 20% of patients even after complete resection. Recently, tumor microenvironment which promotes distant metastasis, or 'pre-metastatic niche', has been indicated to play pertinent roles in postoperative recurrence of cancer. Our aim is to investigate biologic profiles of pre-metastatic niche in pathological Stage I NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eighteen (12.7%) of 141 patients with pathological Stage IA or IB NSCLC who underwent R0 lobectomy between Jan. 2008 and Dec. 2013 developed distant metastasis postoperatively. From archived formalin-fixed paraffin-embedded specimens, these 18 cases of postoperative distant metastasis and matched cases were selected for total RNA extraction. To overcome inherent bias in selecting control patients, one-to-one matched pairs were created using propensity score matching of which model included age, sex, smoking history, and pathological stage. The samples with inadequate mRNA quality/ quantity were excluded. Gene expressions were detected by nCounter (NanoString Technologies, WA, USA) with PanCancer Immune Profilling Panel and PanCancer Progression Panel. Detected expressions were then analyzed and compared between the two groups by nCounter Advanced Analysis (version 2.0.115). Genes with unadjusted P-value < 0.01 were regarded as candidates for further investigation

      4c3880bb027f159e801041b1021e88e8 Result

      From preliminary comparative study on 6 paired cases, distant metastasis group showed upregulations of TPM2, CCL21, SOX2, CXCL12, EGFL7, PTGDS, BGN, PS8L1, ID4 and TGFB, whereas it showed downregulations of MTOR and CCL8 compared to recurrence-free group.

      In LATE-BREAKING ABSTRACT, we will report following results:

      1) Complete dataset of the comparative analysis including all pairs with adequate mRNA.

      2) Immunohistochemstry and/or in situ hybridization of the candidate genes/proteins on pathological sections.volcano plotnew.annotationearly.rec.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Biologic profilings of brain metastasis from NSCLC may subsequently help to understand underlying mechanism of postoperative distant metastasis and ultimately lead to novel targeted therapy.

      Futher details will be added in LATE-BREAKING ABSTRACT.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.09 - Pathology (Not CME Accredited Session) (ID 941)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.09-34 - Prognostic Impact of Invasive Size, Actual Tumor Size, and Mucinous Tumor Size in Invasive Mucinous Adenocarcinoma of the Lung. (ID 12752)

      16:45 - 18:00  |  Presenting Author(s): Tomohito Saito

      • Abstract
      • Slides

      Background

      Currently, tumor size of invasive mucinous adenocarcinoma such as invasive mucinous adenocarcinoma (IMA) is defined by the spread of mucinous component regardless of the existence of tumor cells. The aim of this study is to investigate the prognostic impact of the size of invasive lesion, actual tumor spread, mucinous component in IMA.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Consecutive 19 patients with pN0M0 IMAs which were completely resected between Jan. 2009 and Dec 2015 were retrospectively analyzed. Invasive size (IS), actual tumor size (aTS), and mucinous tumor size (mTS, current T factor) were measured on the identical pathological section, and radiological tumor size (rTS) was also recorded by thorax computed tomography. The prognostic value for postoperative recurrence was evaluated by area under the receiver-operating characteristic (ROC) curves and compared by DeLong’s test.

      4c3880bb027f159e801041b1021e88e8 Result

      Based on mTS, study population included 2 patients T1a, 3 with T1b, 7 with T1c, 4 with T2a, and 3 with T2b. Median age, follow-up, IS, aTS, mTS, and rTS were 75 years, 39 monts, 11mm, 25mm, 26mm and 30mm, respectively. During follow-up, 1 mortality and 3 recurrences were observed. The area under the ROC curves for IS, aTS, mTS,, and rTS were 0.833 (p=0.074)0.979 (p=0.01)1.0 (p=0.007)0.958(p=0.014). The mTS showed no significant difference compared to IS, aTS or rTS.

      figure roc curves for recurrence .jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      In IMA, aTS and mTS might have prognostic value for recurrence. Prospective study with larger population would be necessary to validate the results.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-05 - Biologic Profiling of Brain Metastasis from Non-Small Cell Lung Cancer (ID 13080)

      16:45 - 18:00  |  Presenting Author(s): Tomohito Saito

      • Abstract
      • Slides

      Background

      Bain metastasis develops in approximately 50% of patients with non-small cell lung cancer (NSCLC), resulting in poor prognosis and low health-related quality of life. Immunological microenvironment and functions of ion channels have been indicated to play pertinent roles in epithelial‐to‐mesenchymal transition (EMT) and its reverse mesenchymal‐to‐epithelial transition (MET), crucial steps in distant metastasis, but their actual roles in brain metastasis of NSCLC remains unclear. The aim of this study is to investigate biologic profiles of brain metastasis of NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Formalin-fixed paraffin-embedded (FFPE) samples of brain metastasis and paired primary sites were collected from 3 patients with NSCLC undergoing surgical resection between Jan. 2012 and Dec. 2017. Total RNA was extracted from the archived FFPE, of which integrity was briefly checked by Nanodrop. Gene expression was detected by nCounter (NanoString Technologies, WA, USA) with PanCancer Immune Profilling Panel and custom-made KMU IonChannel Panel that covered selected 100 genes. Detected data was analyzed by nCounter Advanced Analysis (version 2.0.115). Factors with unadjusted P-value < 0.01 were regarded as candidates for further investigation.

      4c3880bb027f159e801041b1021e88e8 Result

      Brain metastasis showed upregulations of MCOLN3 and YTHDF2 (unadjusted P-value= 0.0093 and 0.0063, respectively) compared to the primary site. Conversely, primary site showed upregulations of IFNAR1, TNFRSF4, CXCL11, CT45A1, MAP3K5, TAL1, LAG3 and MARCO.

      In LATE-BREAKING ABSTRACT, we will report following data:

      1) Immunohistochemistry results of the candidate proteins in resected brain metastasis and primary sites of NSCLC from larger population. In situ hybridization is also planned.

      2) Additional data of expression profiles of the candidate genes in sphere cell line from brain metastasis and primary site of NSCLC.

      volcano plotnew.annotationbrainmeta.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Biologic profilings of brain metastasis from NSCLC may subsequently help to understand underlying mechanism and ultimately lead to novel targeted therapy.

      Futher details will be added in LATE-BREAKING ABSTRACT.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.