内容紹介
Exploring the Possibility of New Biomarkers of Immune Checkpoint Inhibitors for Non-Small Cell Lung Cancer(NSCLC)
Summary
Mutation burden in a tumor, presumably involving neo-antigens in the tumor tissue, is also thought to be one of the better predictors for the efficacy of immune checkpoint inhibitors. However, it is difficult to analyze the mutation burden routinely in the clinic. Here, we describe more convenient factors that can be used as surrogate markers of mutation burden. Ninety-four patients with NSCLC who underwent resection in our institution were recruited for this study. Mutation burden and major gene alterations were analyzed by using next generation sequencing. Several immunological parameters were also assessed using immunohistochemistry. Statistical analysis was performed on mutation burden, major gene alternations, immunohistochemistry, and clinical parameters. The median mutation load was 54 mutations(range, 10-363 mutations). Squamous cell carcinoma, EGFR mutation-negativity, and TP53 alteration-positivity were closely connected with higher mutation burden. Multiple regression analysis showed that mutation burden in the tumor could be associated with EGFR mutation and TP53 alteration status.
要旨
免疫チェックポイント阻害薬のバイオマーカーの候補として,われわれは腫瘍組織中の変異遺伝子総数(mutation burden)に注目しているが,日常的に測定することは現実的でない。そこで,従来の臨床学的および免疫学的分子パラメータとmutation burdenの関連性を解析することでmutation burdenと相関があり,日常臨床で用いることのできる因子の抽出を試みた。非小細胞肺癌94例について,次世代シークエンサーを用いた遺伝子解析と手術標本の免疫染色で免疫学的パラメータの評価を行い,臨床的因子も含め解析を行った。94例中,腺癌75例(79.8%),扁平上皮癌19例(20.2%)。mutation burdenの中央値は54(10～363)であった。単変量解析では扁平上皮癌,TP53遺伝子変異陽性,EGFR遺伝子変異陰性においてmutation burdenが高い傾向を認めた。多変量解析ではTP53およびEGFR遺伝子変異の有無によってmutation burdenを予測できる可能性が考えられた。
目次
Summary
Mutation burden in a tumor, presumably involving neo-antigens in the tumor tissue, is also thought to be one of the better predictors for the efficacy of immune checkpoint inhibitors. However, it is difficult to analyze the mutation burden routinely in the clinic. Here, we describe more convenient factors that can be used as surrogate markers of mutation burden. Ninety-four patients with NSCLC who underwent resection in our institution were recruited for this study. Mutation burden and major gene alterations were analyzed by using next generation sequencing. Several immunological parameters were also assessed using immunohistochemistry. Statistical analysis was performed on mutation burden, major gene alternations, immunohistochemistry, and clinical parameters. The median mutation load was 54 mutations(range, 10-363 mutations). Squamous cell carcinoma, EGFR mutation-negativity, and TP53 alteration-positivity were closely connected with higher mutation burden. Multiple regression analysis showed that mutation burden in the tumor could be associated with EGFR mutation and TP53 alteration status.
要旨
免疫チェックポイント阻害薬のバイオマーカーの候補として,われわれは腫瘍組織中の変異遺伝子総数(mutation burden)に注目しているが,日常的に測定することは現実的でない。そこで,従来の臨床学的および免疫学的分子パラメータとmutation burdenの関連性を解析することでmutation burdenと相関があり,日常臨床で用いることのできる因子の抽出を試みた。非小細胞肺癌94例について,次世代シークエンサーを用いた遺伝子解析と手術標本の免疫染色で免疫学的パラメータの評価を行い,臨床的因子も含め解析を行った。94例中,腺癌75例(79.8%),扁平上皮癌19例(20.2%)。mutation burdenの中央値は54(10～363)であった。単変量解析では扁平上皮癌,TP53遺伝子変異陽性,EGFR遺伝子変異陰性においてmutation burdenが高い傾向を認めた。多変量解析ではTP53およびEGFR遺伝子変異の有無によってmutation burdenを予測できる可能性が考えられた。