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Y. Kusumi



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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-057 - Expression of MGAT4a and MGAT5 Are Correlated with Poorer Outcome in Advanced Lung Adenocarcinoma (ID 8714)

      09:30 - 09:30  |  Author(s): Y. Kusumi

      • Abstract

      Background:
      Protein glycosylation is a post-translational modification that is altered in cancer. However, it is yet unclear if there is a correlation between different glycosylation patterns of N-glycan and clinicopathological features. Therefore, we aimed to investigate differing glycosylation in advanced non-small cell lung cancer tissues by lectin expression assays and N-acetylglucosaminyltransferase gene expression analysis.

      Method:
      Formalin-fixed and paraffin-embedded biopsy specimens were obtained from 62 patients with lung adenocarcinoma (ADC) (2009-2011) who were diagnosed at Nihon University Itabashi Hospital. Tumor cells were excised and collected by laser microdissection, and each solubilized glycoprotein and mRNA was extracted. Expression levels of 44 lectins were analyzed by lectin array using a lectin chip. mRNA expression levels of mannosyl (beta-1,4-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase (MGAT3), mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme A (MGAT4a), mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase (MGAT5), fucosyltransferase (FUT)7, and FUT8 were analyzed by qRT-PCR.

      Result:
      Expression levels of Datura stramonium lectin (DSA), Solanum tuberosum lectin (STL), and Aspergillus oryzae lectin (AOL) were significantly higher in drug-resistant ADCs than drug-sensitive ADCs (P = 0.036, 0.0005, and 0.035, respectively). qRT-PCR showed that overexpression of MGAT4a and MGAT5 was detected in 7/62 (11.3%) and 3/62 (4.8%) of ADCs, respectively. The prognosis of patients with MGAT4a and/or MGAT5 positive ADC was worse than those with negative ADC (P = 0.018, log-rank).

      Conclusion:
      The results of the study suggested different glycosylation of N-glycan in lung ADC tissues. MGAT4a and/or MGAT5 overexpression, in particular, may correlate with a poorer response to standard chemotherapy and poorer outcome in advanced lung ADCs.

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    P3.03 - Chemotherapy/Targeted Therapy (ID 719)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P3.03-011 - A Report of BRAF V600E Positive Lung Adenocarcinoma Patient Who Respond Well to Pemetrexed (ID 8806)

      09:30 - 09:30  |  Author(s): Y. Kusumi

      • Abstract

      Background:
      BRAF mutations is one of the important driver oncogene in non-small cell lung cancer (NSCLC), and are known to give the petients worse prognosis as same as KRAS mutations. However, we experienced that a patient with BRAF V600E positive lung adenocarcinoma was responsive to pemetrexed treatment. The patient has been followed for over 7 years without recurrence and metastasis.

      Method:
      Here, we introduce a pemetrexed well respond patient with BRAF mutation positive lung adenocarcinoma. Clinical presentation, radiological features, histopathologic findings and genetic findings of the patient are reported.

      Result:
      A 64 years-old never smoker female who complained bloody sputum visited our hospital. Chest X ray examination showed protrusion of the right first aortic arches. Transbronchial lung biopsy was performed and primary lung adenocarcinoma was diagnosed. Brain metastasis was suspected by magnetic resonance imaging. The patient was initially given combined chemotherapy with CDDP+VNR and Radiation therapy (60Gy). But after six months, tumor progression was found. Therapeutic agent was changed to 600mg single pemetrexed as outpatient chemotherapy for 14 months. Computed tomography showed reduction of tumor mass. Then, the patient has been still followed without any anti-cancer treatment. It passed for 7 years after diagnosis. The oncogenic driver mutations of the present patient were investigated in another study. Immunohistochemistry and DNA sequencing analysis showed the existence of BRAF mutation V600E in the present case.

      Conclusion:
      BRAF mutation in NSCLC was reported not associated with enhanced chemosensitivity. However, pemetrexed was effective to the present BRAF V600E positive lung adenocarcinoma patient.